TOPNOTCH MEDICAL BOARD PREP BIOCHEMISTRY HANDOUT

TOPNOTCH MEDICAL BOARD PREP BIOCHEMISTRY HANDOUT (PART 1) BY FRINZ MOEY C.
RUBIO, MD
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This handout is only valid for the October 2022 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.

This handout is only valid for the October 2022 PLE batch. This will
IMPORTANT LEGAL INFORMATION be rendered obsolete for the next batch since we update our

The handouts, videos and other review materials, provided by Topnotch Medical Board handouts regularly.
Preparation Incorporated are duly protected by RA 8293 otherwise known as the Intellectual
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Board Preparation Incorporated Program or c) is the recipient of this electronic
communication. No part of the handout, video or other review material may be reproduced,
shared, sold and distributed through any printed form, audio or video recording, electronic
1. Chemical Reactions
medium or machine-readable form, in whole or in part without the written consent of 2. Properties of Water GENERAL CHEMISTRY
Topnotch Medical Board Preparation Incorporated. Any violation and or infringement, 3. Acids and Bases https://qrs.ly/m9e032u
whether intended or otherwise shall be subject to legal action and prosecution to the full
extent guaranteed by law. 4. Functional Groups

DISCLOSURE FUNDAMENTAL
The handouts/review materials must be treated with utmost confidentiality. It shall be the DEFINITION
LAWS
responsibility of the person, whose name appears therein, that the handouts/review
materials are not photocopied or in any way reproduced, shared or lent to any person or Law of
Mass of material before reaction = after reaction
disposed in any manner. Any handout/review material found in the possession of another Conservation
person whose name does not appear therein shall be prima facie evidence of violation of RA Mass is neither created nor destroyed
of Mass
8293. Topnotch review materials are updated every six (6) months based on the current
Chemical compound, regardless of source or method
trends and feedback. Please buy all recommended review books and other materials listed Law of Definite
below. of preparation, have the same composition
Composition
THIS HANDOUT IS NOT FOR SALE! (proportion by mass)

If two elements form more than one compound,
Law of Multiple
INSTRUCTIONS Proportion
masses of one element combined with fixed mass of
To scan QR codes on iPhone and iPad another are in ratio of small whole numbers
1. Launch the Camera app on your IOS device
2. Point it at the QR code you want to scan
3. Look for the notification banner at the top 1.1 CHEMICAL REACTIONS
of the screen and tap CHEMICAL REACTION
To scan QR codes on Android
1. Install QR code reader from Play Store • Refers to a process in which a substance (or substances) is changed
2. Launch QR code app on your device into one or more new substances
3. Point it at the QR code you want to scan • Example: burning love letters from your ex
4. Tap browse website
On the other hand, physical change occurs when you simply cut the love
Approach to Topnotch Biochemistry by Dr. Banzuela letters of your ex (lalo na if umaasa ka na magkakabalikan pa kayo! &
-)
,
+
*
)
(
'

• Please have the following Topnotch materials at hand I know this is a very basic concept, but this is very important to strengthen
o Topnotch main handout will serve as your main reference material your basic chemistry concepts! Moreover, not all medical students have a
o Topnotch supplement handout will serve as a quick refresher BS degree in Science. Chill lang tayo! .
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prior (few weeks) before the board.

Dr. Rubio
• Please buy the following: CHEMICAL EQUATION

o Michael W. King, Integrative Medical Biochemistry Examination & • A standard method for communicating with one another about
Board Review chemical reactions
o Lieberman & Ricer, Biochemistry, Molecular Biology & Genetics • Uses chemical symbols to show what happens during a chemical
Board Review Series 7th edition reaction
o USMLE first aid
• Study smart!
o Memorization is not enough; you must listen & understand the
From Chang General Chemistry: The Essential Concepts, 6th edition
concepts well.
o Comprehend the applications of biochemistry in certain disease “plus” sign • Means “reacts with”
conditions. “arrow” sign • Means “to yield”
• The symbolic expression, chemical equation, can be read as:

BIOCHEMISTRY PART 1 – Molecular hydrogen reacts with molecular oxygen to yield

water
STRUCTURAL BIOCHEMISTRY & • In the equation above, we refer to H2 and O2 as reactants, while
H2O as products:
NUTRITION
By Frinz Moey C. Rubio, MD
Contributors: Ronnie E. Baticulon, MD; Angela L. Recuenco, MD;
From Chang General Chemistry: The Essential Concepts, 6th edition
James Daniel E. Omalin, MD, Madelaine Johanna Abraham, MD

Internal Medicine Resident, St. Luke’s Medical Center – Quezon City (2022 – present)
• Starting materials in a chemical
Junior Faculty, San Beda College of Medicine (2020 – 2021) Reactants
University of the Philippines College of Medicine Class 2020, Cum Laude (5th Rank) reaction
UP Manila Gawad Chancellor Most Outstanding Student AY 2019-2020 Awardee • Substance formed as a result of a
Ten Outstanding Medical Students, APMC-SN NCR-SL AY 2019-2020 Awardee Products
chemical reaction
This handout is designed to discuss basic concepts of chemistry,
structures and properties of biomolecules, and important topics of REVERSIBLE VS IRREVERSIBLE REACTIONS
nutrition in the clinical and public health setting. This will also prepare • Irreversible reactions are usually represented by a single arrow
the student for the Metabolism and Genetics part of Biochemistry. After
reading the handout, please take time to review the appendix which is a
(→) wherein the tail-side represents the side of the reactants,
summary of important board correlates. I am hoping that this handout will while the arrowhead-side represents the side of the products
be very useful in your Biochemistry Exam. See you around… virtually! " %
$
# • Reversible reactions are usually represented by a bidirectional

Dr. Rubio arrow (⇌)
MODULE PAGE
1. Review of Chemistry Concepts 1
2. Structure of Amino Acids & Proteins 5
3. Structure of Carbohydrates 13 REACTANTS PRODUCTS

4. Structure of Lipids 15 Arrow pointing to the • Represents FORWARD REACTION

5. Structure of Nucleotides 18 RIGHT • Reactants → Products
6. Nutrition 21
Arrow pointing to the • Represents REVERSE REACTION
7. Vitamins & Minerals 26
8. Complex Molecules 33
LEFT • Products → Reactants

9. General Enzymology 36 When the rates of the FORWARD and REVERSE reactions are EQUAL,
10. Digestion & Absorption of Macronutrients 39 and the concentrations of the reactants & products no longer change
11. Expanded National Nutritional Survey (ENNS) 40 with time, CHEMICAL EQUILIBRIUM IS ACHIEVED.
Dr. Rubio
Appendix: Board Correlates & Quick Review Appendix
TOPNOTCH MEDICAL BOARD PREP BIOCHEMISTRY HANDOUT (PART 1) BY FRINZ MOEY C. RUBIO, MD Page 1 of 41
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TOPNOTCH MEDICAL BOARD PREP BIOCHEMISTRY HANDOUT (PART 1) BY FRINZ MOEY C. RUBIO, MD
ENERGY CHANGES IN CHEMICAL REACTIONS TERM DEFINITION
• Heat refers to the transfer of thermal energy between bodies that energy transfer between two bodies at
Heat (q)
are at different temperatures different temperatures

energy transfer between a system & its
Heat generated by the combustion process is
Exothermic Work (w) surroundings in the form of compression or
transferred from the SYSTEM OF CHEMICAL
process expansion of gas
REACTION → SURROUNDINGS
total energy attributed to particles of matter
Endothermic Heat is supplied by the SURROUNDINGS → Internal
& their interactions within a system,
process SYSTEM OF CHEMICAL REACTION Energy (U)
composed of thermal energy & chemical energy

Enthalpy(H) energy of a reaction
ENTROPY AND THE LAWS OF THERMODYNAMICS
Entropy (S) degree of disorderliness
• Thermodynamics: study of the interconversion of heat and
Heat amount of heat required to raise temperature
other kinds of energy
Capacity (c) of an object/substance by 1 degree
o The laws of thermodynamics provide useful guidelines for
Specific amount of heat required to raise temperature
understanding the energetics and direction of processes
Heat of an object per gram

ZEROTH LAW OF THERMODYNAMICS
REACTION EXOTHERMIC ENDOTHERMIC
• States that if two bodies are each in thermal equilibrium with a
third body, they are also in equilibrium with each other HEAT IS absorbed released

ENTHALPY -H +H
To simply this, remember your transitive property in Math (ugh)
ENTROPY +S -S
If A = C, and B = C, then A = C

Dr. Rubio

1ST LAW OF THERMODYNAMICS
• Energy can be converted from one form to another, but cannot be THERMOCHEMISTRY
created nor destroyed https://qrs.ly/wde034g

SIGN CONVENTIONS FOR HEAT
• Endothermic process METHODS OF HEAT TRANSFER
Plus sign (+) • Heat is absorbed by the SYSTEM OF • There are three basic methods involved in the transfer of heat
CHEMICAL REACTION from the heat source to another object
• Exothermic process
Negative sign (-)
• Heat is released to the SURROUNDINGS CONDUCTION CONVECTION RADIATION

Remember this: If the FORWARD REACTION is an exothermic process; Heat transfer by

the REVERSE REACTION is an endothermic process; vice versa movement of fluid Heat transfer by
Dr. Rubio

Heat transfer – air or water – which heat is

between objects when the heated transmitted
ENTROPY via direct contact fluid is caused to without any
• Measure of the change in randomness or disorder of the reactants move away from medium
and products the heat source
• The greater the randomness or disorder, the greater the entropy Evaporation of air
from hot water
2nd LAW OF THERMODYNAMICS surface, and
• The entropy of the universe increases in a spontaneous process, Heat from the sun
precipitating as
and remains unchanged in an equilibrium process Touching heated or lightbulb via
rain when air is
• In simpler terms: pan electromagnetic
cooled
Entropy of the universe = Entropy of the reaction + Entropy waves
Evaporative
of the surroundings cooling from
perspiration
3rd LAW OF THERMODYNAMICS
• The entropy of a system approaches a constant value when FACTORS AFFECTING THE CHEMICAL EQUILIBRIUM
absolute temperature reaches absolute zero • Chemical equilibrium represents a balance between forward

And this actually makes sense, because in absolute zero temperature, the and reverse reactions:
molecules are not moving, hence entropy is zero (there is no chaos). Shift to the • Net reaction favored is from LEFT → RIGHT
Pero walang masama mag-move… on 2 7
6
5
4
3 RIGHT • Formation of PRODUCTS is favored
Dr. Rubio
Shift to the • Net reaction favored is from RIGHT → LEFT

THERMODYNAMIC PROCESS LEFT • Formation of REACTANTS is favored
• Defined as the energetic evolution of a thermodynamic system
proceeding from an initial state to a final state (described by LE CHATELIER’S PRINCIPLE
process quantities) • General rule that helps us to predict the direction in which an
• Commonly studied thermodynamic processes: equilibrium will move when there is a change in:
Occurs without loss or gain of o Concentration
Adiabatic process o Pressure
energy by heat
Isenthalpic process Occurs at constant enthalpy o Volume
o Temperature
Isentropic process Occurs at constant entropy
• States that if an external stress is applied to a system at equilibrium,
Isobaric process Occurs at constant pressure
the system adjusts in such a way that the stress is partially offset as
Isochoric (isometric,
Occurs at constant volume it tries to reestablish equilibrium (stress: change in
isovolumetric) process
concentration, pressure, volume, or temperature that
Isothermal process Occurs at constant temperature removes a system from the equilibrium state
Occurs without a change in the
internal energy RESPONSE OF A CHEMICAL EQUILIBRIUM TO STRESSORS
Steady-state process All parameters are held constant Increase in
(heat, enthalpy, pressure, volume, concentration of a Shifts AWAY from the substance
etc.) substance
Decrease in
concentration of a Shifts TOWARDS the substance
substance
Increase in pressure WATER FORMS HYDROGEN BONDS
Shifts TOWARDS fewer moles of gas
of the system • Relatively weak and transient, with a half-life of a few picoseconds
Decrease in pressure • On average, each molecule in liquid
Shifts TOWARDS more moles of gas
of the system water associates through hydrogen
Increase temperature bonds with 3.5 others
Favors ENDOTHERMIC REACTION
of the system • An unshielded hydrogen nucleus
Decreases covalently bound to an electron-
temperature of the Favors EXOTHERMIC REACTION withdrawing oxygen, nitrogen or sulfur
system atom can interact with an unshared
NO SHIFT electron pair on another sulfur, oxygen,
A catalyst increases the rates of both or nitrogen atom.
Catalyst
forward and reverse reactions by the

• Therefore, if you see a hydrogen atom

same amount
attached to sulfur, oxygen, or nitrogen:
1. That molecule can form
LE CHATELIER’S hydrogen bonds (dotted lines)
PRINCIPLE 2. That molecule will now be
https://qrs.ly/jce0354 considered polar
3. That molecule will dissolve in
To have a visual understanding of Le Chatelier’s Principle. Please watch the
water (hydrophilic)
Figure 2-3. Rodwell VW, et al. Harper’s Illustrated Biochemistry. 30th ed. 2015
attached QR code!
Dr. Rubio
• In contrast, molecules that do not contain hydrogen atoms
attached to S, O, N will be non-polar and hydrophobic (e.g.,

OXIDATION & REDUCTION

OXIDATION REDUCTION benzene C6H6 → Hydrogen is attached only to carbon)

• Losing electrons • Gaining electrons As I’ve mentioned earlier, “LIKE DISSOLVES LIKE!” Polar substances
• Losing hydrogen • Gaining hydrogen dissolve in water hence they are also known as HYDROPHILIC substances
(water-loving).
• Gaining oxygen • Losing oxygen
Increase in oxidation number Decrease in oxidation number In contrast, substances that are non-polar cannot be dissolved in water,
hence they are known as HYDROPHOBIC substances (water-fearing).
(e.g., Fe2+ → Fe3+) (e.g., Fe3+ → Fe2+) Dr. Rubio
Reaction RELEASES ENERGY Reaction STORES ENERGY

WATER HAS A HIGH DIELECTRIC CONSTANT

Oxidized agent Reduced agent • Water greatly decreases the force of attraction between charged
= Reducing agent = Oxidizing agent and polar species, which makes it an excellent solvent (e.g., NaCl

Recall the famous mnemonic: dissociates into Na+ and Cl- ions)
LEORA: Loses Electrons, Oxidized = serves as Reducing Agent
GEROA: Gains Electrons, Reduced = serves as Oxidizing Agent WATER IS AN EXCELLENT NUCLEOPHILE
Dr. Rubio
• Nucleophilic attack by water generally results in the cleavage of

the amide, glycoside, or ester bonds that hold biopolymers

OXIDATION AND together
REDUCTION
https://qrs.ly/7ke035o

1.2 PROPERTIES OF WATER
This phenomenon is known as hydro-lysis (to lyse the bonds between
WATER molecules)
• Predominant chemical component of living
Dr. Rubio
WATER IS AMPHOTERIC
organisms
• The water molecule is an irregular, H2O + H2O ⇌ H3O+ + OH-
slightly skewed tetrahedron: • Water is both an acid and a base
o Oxygen at its center • It can dissociate into hydronium (H3O+) and hydroxide (OH-) ions.
o Two hydrogens and the 2 lone pairs of

✔ KEY CONCEPTS
electrons occupy the corners

• HydroPHILIC (water-loving): compounds that dissolve
easily in water; generally charged or polar
PROPERTIES OF WATER • HydroPHOBIC (water-fearing): nonpolar molecules such as
WATER IS A DIPOLE lipids and waxes, which dissolve in chloroform and benzene
• A molecule with electrical charge distributed asymmetrically
about its structure
1.3 ACIDS AND BASES
• Hydrogen atoms: Partially positive
• Unpaired electrons of oxygen: Partially pH
negative pH = – log [H+]
• Here you can see two molecules of water joined
• Defined as the negative log of the hydrogen ion concentration
by a hydrogen bond (dotted line), because the
• Measure of acidity or alkalinity
partially positive end attracts the partially
negative end • Physiologic pH: 7.35 to 7.45
✔ KEY CONCEPTS
The oxygen found at the center attracts more electron (negatively • Acids: low pH, high H+ concentration [H+]
charged particle) towards it; this makes the oxygen side a (-) pole; and
• Bases: high pH, low H+ concentration [H+]
hydrogen side a (+) pole → making water a POLAR substance.

The concept of polarity is very important when we talk about solubility:

“LIKE DISSOLVES LIKE!” Substances w/ similar characteristics will
dissolve in each other: polar substances dissolve with polar substances;
non-polar substances dissolve with non-polar substances.

Remember: opposites attract! The partially positive end of one water

molecule attracts the partially negative end of another water molecule →
forming a hydrogen bond
Dr. Rubio

• ACIDS are proton donors
• BASES are proton acceptors

• pKa values express the strengths of acids
Smaller pKa value The STRONGER the acidity of a substance ✔ KEY CONCEPTS
Larger pKa value The WEAKER the acidity of a substance • The STRONGER THE ACID, the WEAKER ITS CONJUGATE
BASE
HENDERSON-HASSELBALCH EQUATION • The WEAKER THE ACID, the STRONGER ITS CONJUGATE
BASE
• Used to calculate the concentration of a weak acid [HA] and its
conjugate base [A ] in an aqueous solution
-
o An increase in [HA] lowers pH, while an increase in [A-] elevates pH BUFFERS

• Useful for:
o Titration of amino acids
o Predicting shifts in the bicarbonate buffer system
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-
o Predicting distribution of drugs

From Harper’s Illustrated Biochemistry. 30th ed. 2015
• Resist a change in pH when protons are produced or consumed

• Maximum buffering occurs ± 1 pH unit on either side of pKa
• Physiologic buffers include bicarbonate, orthophosphate, and
proteins

1.4 FUNCTIONAL GROUPS
• A functional group is a characteristic group of atoms or bonds that
possess a predictable chemical behavior
• “R-“: refers to the remainder of the compound, usually a
pKA Table hydrocarbon (made up of hydrogen and carbon)
From https://www.masterorganicchemistry.com/2010/09/29/how-to-use-a-pka-table/

From Klein Organic Chemistry, 3rd Edition

Above are the common functional groups encountered in biochemistry. Familiarize yourselves on their structures so that you will have an idea on how they
look like as you read the rest of this handout. Enjoy! .
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Dr. Rubio
• Other terminologies important in understanding the structure of
biomolecules: 2. STRUCTURE OF AMINO ACIDS & PROTEINS
• An organic chemical compound
Hydrocarbon 1. General Structure of Amino Acids
exclusively of hydrogen and carbon 2. Classification of Amino Acids
chains
atoms 3. Essential and Non-Essential Amino Acids
4. Properties of Amino Acids
• Composed of straight-chained, 5. Abbreviations of Amino Acids
Aliphatic branched, or cyclic compounds 6. Overview of Proteins
compounds • Can be saturated (alkanes) or 7. Structural Organization of Proteins
8. Globular Proteins
unsaturated (alkenes, alkynes) 9. Fibrous Proteins
Aromatic 10. Structure of Immunoglobulins
• Contains benzene rings
compounds
Monomer • Basic unit of a polymer 2.1 GENERAL STRUCTURE OF AMINO ACIDS
• Represents 2 monomers attached to
Dimer • More than 300 amino acids have been described
each other
• Only 20 are commonly found in mammalian proteins
• Represents more than 2 monomers
Polymer • Except for proline, each amino acid has:
attached to each other
o A carboxyl group (COOH): an acid (can donate a proton)
• Polymer made up of identical o An amino group (NH2): a base (can accept a proton)
Homopolymer
monomers o A distinctive side chain (R-group): structure of R-group
• Polymer made up of 2 or more dictates the function of the amino acid in the protein
Heteropolymer
different monomers
• Also known as an asymmetric carbon
• Refers to a carbon which has 4 different
atoms or groups of atoms attached to it
Chiral carbon

Structure of 2-butanol. (Center of the structure
represents a chiral carbon with 4 different
atoms/groups of atoms attached to it)
From Klein Organic Chemistry, 3rd Edition
• It refers to the 1st carbon atom that
attaches to a functional group in an
General Structure of α-Amino Acids
α-carbon organic compound From Self-Assessment and Review of Biochemistry, 2nd Edition
• The 2nd carbon atom is termed as β- • Most of the amino acids are α-amino acids
carbon… and so on! o It means both amino and carboxyl groups are attached to the
α-carbon atom
• In non-α-amino acids, neither carboxyl group nor amino group is
attached to the α-carbon atom

Non-α-amino acids present in tissues in free form are: β-alanine,

β-aminoisobutyrate, and γ-aminobutyrate.
Dr. Rubio

• At physiologic pH (7.4):

o Carboxyl group is dissociated or deprotonated → COO-

o Amino group is protonated → NH3+
2.2 CLASSIFICATION OF AMINO ACIDS

NON-POLAR AMINO ACIDS POLAR UNCHARGED AMINO ACIDS CHARGED AMINO ACIDS
Positive or negative net charge
Zero net charge Zero net charge
(acidic or basic)
Forms hydrophobic interactions Forms hydrogen bonds Forms ionic interactions
Found in the interior of the protein Found on the surface of a protein Found on the surface of a protein
Glycine Phenylalanine -OH -SH AMIDE ACIDIC BASIC
Alanine Tryptophan Serine Cysteine Asparagine Aspartate Arginine
Valine Methionine Threonine Glutamine Glutamate Lysine
Isoleucine Proline Tyrosine Histidine
Leucine

NONPOLAR AMINO ACIDS Tetanospasmin (product of C tetani) prevents the release of glycine from
Renshaw cells. Thus, muscle will continuously contract leading to spastic
paralysis.

Dr. Rubio
ALANINE

GLYCINE ALANINE VALINE • Carrier of ammonia and of the carbons of pyruvate from skeletal
muscle to liver
• Together with glycine, constitutes a major fraction of free amino
acids in the blood

Alanine, Glutamine, Glutamate are important in ammonia disposal in the

LEUCINE ISOLEUCINE body. This will be further discussed by Dr. Baticulon.

Dr. Rubio
GLYCINE

VALINE, LEUCINE, ISOLEUCINE

• Has the smallest side chain; only achiral amino acid among the • Branched-chain amino acids whose metabolites accumulate in
20 AAs maple syrup urine disease
• Used in the first step of heme synthesis
Glycine + Succinyl CoA à δ-ALA
• Used in synthesis of purines and creatine
• Conjugated to bile acids, drugs, and other metabolites

• Major inhibitory neurotransmitter in the spinal cord PHENYLALANINE TRYPTOPHAN
ASPARTATE, GLUTAMATE
• Negatively charged at neutral pH because of the carboxylate
group
METHIONINE

PROLINE
• Participate in ionic interactions
• Serve as proton donors
PHENYLALANINE • Glutamate is the precursor for GABA and glutathione
• Accumulates in phenylketonuria

Glutamate is the major excitatory neurotransmitter of the CNS. GABA is

• Precursor of tyrosine the major inhibitory neurotransmitter of the BRAIN.

TRYPTOPHAN Glycine is the major inhibitory neurotransmitter of the SPINE.

Dr. Rubio
• Has the largest side chain

• Precursor for niacin, serotonin, and melatonin BASIC AMINO ACIDS

MNEMONIC TRYPTOPHAN DERIVATIVES

TRYp Mo Siya, ‘No?
TRYptophan
Melatonin HISTIDINE
ARGININE
Serotonin
Niacin

METHIONINE
LYSINE
• Source of methyl groups in metabolism:
o Involved in transfer of methyl groups as S-adenosylmethionine HISTIDINE, ARGININE, LYSINE

(SAM) • Proton acceptors
• Precursor of homocysteine and cysteine • At neutral pH:

PROLINE o Arginine and lysine are positively charged

o Histidine, being a weak base, has no charge
• Not an amino, but an imino acid
• Contributes to the fibrous structure of collagen and interrupts α- HISTIDINE

helices in globular proteins • Precursor of histamine
• Also used in the diagnosis of folic acid deficiency (FIGLU excretion
UNCHARGED POLAR AMINO ACIDS test)
• Concentration in the brain hypothalamus varies in accordance
with the circadian rhythm

SERINE THREONINE

SERINE, THREONINE, TYROSINE

• Contain a polar hydroxyl group
• Site for O-linked glycosylation and phosphorylation of proteins

• Tyrosine is the precursor of several compounds: ARGININE
o Phenylalanine → Tyrosine → L-dopa → Dopamine → • Precursor of creatinine, urea, and nitric oxide
Norepinephrine → Epinephrine
o Also a precursor for thyroxine and melanin LYSINE

• Precursor of carnitine
MNEMONIC PHENYLALANINE / TYROSINE DERIVATIVES
Pare, True Love Does Not Exist
21ST AMINO ACID
Phenylalanine →Tyrosine → L-dopa → Dopamine →
Norepinephrine → Epinephrine SELENOCYSTEINE

• Found in a handful of proteins, including certain peroxidases and
reductases, where it participates in the catalysis of electron
transfer reactions
• A selenium atom replaces the sulfur of its structural analog,
TYROSINE CYSTEINE cysteine
• Inserted into polypeptides during translation but is not specified
by a simple three-letter codon

ASPARAGINE GLUTAMINE

ASPARAGINE, GLUTAMINE CLASSIFICATION OF

• Have a carbonyl group and an amide group that can also form AMINO ACIDS
hydrogen bonds https://qrs.ly/p3e036y
• Asparagine is the site for N-linked glycosylation of proteins
• Glutamine is deaminated by glutaminase resulting in the
formation of ammonia, and is a major carrier of nitrogen to the 2.3 ESSENTIAL AND NON-ESSENTIAL AMINO ACIDS
liver from peripheral tissues
• Essential: refers to amino acids which cannot be synthesized in
CYSTEINE the body; hence they are ESSENTIAL IN DIET
• Contains a sulfhydryl group that is an active part of many • Non-essential: refers to amino acids which can be synthesized in
enzymes the body; hence they are NON-ESSENTIAL IN DIET
• Participates in the biosynthesis of coenzyme A • Semi-essential: refers to amino acids which are required in
• Two cysteines can be connected by a covalent disulfide bond to growing children, but not essential in adults

form cystine • Phenylalanine
Disulfide bonds formed by cystine residues causes kinking of hair. • Valine
Disruption of these bonds (using heat) may straighten hair temporarily. • Threonine

Dr. Rubio
• Tryptophan

Essential amino acids • Isoleucine
ACIDIC AMINO ACIDS • Methionine
• Histidine
• Leucine

ASPARTATE GLUTAMATE • Lysine
Semi-essential amino acid • Arginine AMINO ACIDS ABBREVIATED BASED ON PHONETICALLY
Non-essential amino acids • All other amino acids SOUNDING LETTERS
3-LETTER 1-LETTER

Warning: Please take note that in some Biochemistry textbooks, they

include arginine as an essential amino acid. Hence, this can be a cause of ABBREVIATION ABBREVIATION
confusion. Arginine Arg R (aRginine)

Dr. Rubio Asparagine Asn N (asparagiNe)
Aspartic acid Asp D (asparDic acid)
ESSENTIAL & SEMI-ESSENTIAL AMINO Glutamic acid Glu E (glutEmic acid)
MNEMONIC
ACIDS Glutamine Gln Q (Qtamine)
PVT TIM HALL, always ARGues, never TYRes Phenylalanine Phe F (Fenylalanine)
(A is always ARGinine, T is never TYRosine) Tyrosine Tyr Y (tYrosine)

Phenylalanine Histidine Tryptophan Trp W (tWiptophan)

Valine Arginine (semi-essential) Lysine Lys K (letter close to L)
Threonine Leucine
Tip: Read the phonetic mnemonic aloud while studying this portion of the
Tryptophan Lysine handout! It helps!
Isoleucine
Dr. Rubio
Methionine
2.6 OVERVIEW OF PROTEINS
2.4 PROPERTIES OF AMINO ACIDS • Most abundant and functionally diverse molecules in living
• Except for glycine, all amino acids are chiral systems
o L-configuration: all amino acids in human proteins • Proteins are linear polymers of amino acids
o D-configuration: bacterial cell walls, antibiotics o Monomers: amino acids
Review: Chiral carbon has 4 different atoms or group of atoms o Polymers: proteins
around it. Glycine’s alpha carbon is not chiral (achiral) since two H’s • Perform diverse functions:
(which are similar) are attached around that carbon hence Glycine has no o Regulate metabolism
chiral center. All the rest are chiral, and if chiral it will have a o Facilitate muscle contraction
nonsuperimposable mirror image (enantiomer). o Provide structural framework
Dr. Rubio
o Shuttle molecules in the bloodstream (especially hydrophobic

molecules)
o Serve as component of the immune system

Refers to the set of all the proteins expressed by

Proteome
an individual cell at a particular time
Aims to identify the entire complement of
proteins elaborated by a cell under diverse
conditions
Adapted from Lippincott Illustrated Reviews Biochemistry, 7th Edition
A major goal is the identification of proteins and
Proteomics
• Amino acids can have negative, zero, or positive charge depending of their posttranslational modifications whose
on pH of the aqueous environment appearance or disappearance correlates with
• An amino acid bears no net charge (zwitterion) at its isoelectric physiologic phenomena, aging, or specific
pH (pI) diseases

• Because they can accept or donate protons, amino acids can Genome contains the manuscript of life. It remains the same throughout.
serve as buffers in aqueous solutions Proteome refers to the variety of proteins formed from the genome.

Dr. Rubio
Review:
Acids: donates protons (H+)
Bases: accepts protons (H+) 2.7 STRUCTURAL ORGANIZATION OF PROTEINS

Dr. Rubio

Form II is the zwitterion for alanine (neutral charge overall). Acidic

amino acids have a pI <7. Basic amino acids have pI> 7.

Dr. Rubio

2.5 ABBREVIATIONS OF AMINO ACIDS
AMINO ACIDS WITH UNIQUE FIRST LETTER PRIMARY STRUCTURE
3-LETTER 1-LETTER • Determined by the amino acid sequence of a protein
• Peptide bonds attach the α-amino group of one amino to the α-
ABBREVIATION ABBREVIATION
Cysteine Cys C carbonyl group of another
Histidine His H
Isoleucine Ile I
Methionine Met M
Serine Ser S
Valine Val V
PEPTIDE BONDS
AMINO ACIDS ABBREVIATED BASED ON THE COMMONLY • Partial double-bond character (represents 1.5 bonds)
OCCURRING AMINO ACIDS • Rigid and planar
3-LETTER 1-LETTER • Generally, in the trans-configuration

ABBREVIATION ABBREVIATION • Disrupted by hydrolysis through prolonged exposure to a strong
Glycine Gly G acid or base at elevated temperatures

Alanine Ala A Peptide bond formation is a dehydration chemical reaction. Hence,
Leucine Leu L addition of water can cause lysis or destruction of this bond (hydrolysis)
Proline Pro P (when exposed to strong chemicals at elevated temperatures or catalyzed
Threonine Thr T by enzymes)
Dr. Rubio

N-TERMINUS AND C-TERMINUS

• Proteins are naturally synthesized from the N-terminus (NH3
end) to the C-terminus (COOH end)

• Read the amino acid sequence of a primary structure from the N-

terminus to C-terminus
Recall that amino acids that can disrupt the α-helix structure are proline
and glycine.

Dr. Rubio
• Salient functions of N- and C-terminus of AA sequences:

• Contains targeting signals (targets protein
N-terminus
to a specific organelle)
• Contains retention signals for protein
sorting (keeps the protein in the
endoplasmic reticulum)
C-terminus DOMAINS
• Can be modified post-translationally to allow
the protein to be inserted into a membrane • Fundamental functional and three-dimensional structural units
without having a transmembrane domain of polypeptide

Mnemonic: N-terminus – allows N-try of protein into an organelle via Motifs refer to structural modifications
targeting signals; C-terminus Contains protein inside the organelle via Domains may vary and have specific functional effect
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retention signals

Dr. Rubio
QUATERNARY STRUCTURE
• Number and types of polypeptide units of oligomeric proteins and
SECONDARY STRUCTURE their spatial arrangement
• The folding of short (3–30 residue) contiguous segments of o Monomeric vs Dimeric proteins
polypeptide into geometrically ordered units o Homodimers vs Heterodimers

• Stabilized by hydrogen bonding A protein can form quaternary structure if there are 2 or more chains.
Hemoglobin A1 has 2 alpha & 2 beta chains; thus, it can form quaternary
ALPHA HELIX structure. Monomeric means having only 1 polypeptide chain/subunit; so
• Most common secondary structure it cannot form quaternary structure (ex. Myoglobin).
Dr. Rubio
• Spiral structure with polypeptide backbone core, with side chains

extending outward CHAPERONES
• 3.6 AA per turn • Specialized group of proteins required for the proper folding of
• Examples: many species of proteins
o Keratin (100% α-helix) • Prevent aggregation, thus providing an opportunity for the
o Hemoglobin (80% α-helix) formation of appropriate secondary structural elements and their

Review: The amino acids that can disrupt the α-helix structure are proline subsequent coalescence into a molten globule
and glycine • Can also “rescue” proteins that have become thermodynamically
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trapped in a misfolded dead end by unfolding hydrophobic

BETA SHEET regions

• Amino acid residues form a zigzag or pleated pattern In short, chaperones help fold proteins to their final configuration.
Dr. Rubio
• R groups of adjacent residues project in opposite directions

• Sheets can be parallel or antiparallel DENATURATION
• Examples:
• Results in the unfolding and disorganization of the protein’s
o Amyloid
secondary and tertiary structures
o Immunoglobulin
• Not accompanied by hydrolysis of peptide bonds
• Results from denaturing agents:
o Heat, organic solvents, mechanical mixing, strong acids or
bases, detergents, ions of heavy metals (e.g., lead, mercury)
• May be reversible, but most proteins remain permanently
disordered

NON-REPETITIVE SECONDARY STRUCTURES
• Less regular structures forming loops and bends

MOTIFS
• Supersecondary structures produced by packing side chains from Note that denaturation does not affect a protein’s primary structure.
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adjacent secondary structural elements close to each other

• Examples are β-α-β unit, Greek key, β-meander, β-barrel
PROTEIN-FOLDING DISORDERS

TERTIARY STRUCTURE PRION DISEASES

• Overall 3-dimensional shape of the protein • Fatal neurodenegerative diseases characterized by spongiform
o Globular proteins vs Fibrous proteins changes, astrocytic gliomas, and neuronal loss resulting from the
• The assembly of secondary structural units into larger functional deposition of insoluble protein aggregates in neural cells
units such as the mature polypeptide and its component domains • Examples:
• Stabilized by disulfide bonds, hydrophobic interactions, o Creutzfeldt-Jakob disease in humans
hydrogen bonds, and ionic interactions o Scrapie in sheep
o Bovine spongiform encephalopathy in cattle
o Kuru in cannibalistic tribes
Majority of oxygen is transported in the blood through hemoglobin.
In contrast, majority of carbon dioxide is transported as dissolved
bicarbonate anion. Note that carboxyhemoglobin refers to carbon
monoxide bound to hemoglobin, while carbaminohemoglobin refers
to carbon dioxide bound to hemoglobin.

Dr. Rubio
HEMOGLOBIN
• Heme protein found exclusively in red blood cells (RBCs)
• Functions:
o Transport of O2 from the lungs to capillaries
o Transport of CO2 from tissues to the lungs
• Exists in 2 configurations
o T (taut) form: low oxygen affinity
o R (relaxed) form: high oxygen affinity (300x)
• Hemoglobin binds up to 4 molecules of O2 with increasing affinity
(positive cooperativity)

Heme has iron and histidine. Hemoglobin has 4 polypeptides hence can
form quaternary structure. Oxygen binds to Hb if Hb is in the R state, &
its iron is in the Fe2+ or ferrous state! Positive cooperativity: 1st to
This will be discussed more extensively in Microbiology. But what I want commit is the hardest to let go (it is the rationale for the sigmoidal
you to remember here are the forms of normal and abnormal prion configuration of the O2 dissociation curve)
protein.
Dr. Rubio

PrPc represents the normal protein which has an α-helix structure; on the OVERVIEW OF HEMOGLOBIN FORMATION
other hand, PrPsc represents the abnormal protein which has a β-sheet • Basic steps in the formation of hemoglobin A
structure. The shift from α-helix → β-sheet makes PrPsc resistant from (1) 2 succinyl coenzyme A + 2 glycine → 1 pyrrole
proteases and other chemicals. Accumulation of PrPsc would lead to (2) 4 pyrroles → protoporphyrin IX
spongiform neurodegeneration of the brain → CNS dysfunction → (3) Protoporphyrin IX + Fe2+ → Heme
coma → death. (4) Heme + Polypeptide → Hemoglobin chain (α or β)
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(5) 2 α chains + 2 β chains → Hemoglobin A

ALZHEIMER DISEASE
• Most common and most important degenerative disease of the STRUCTURE OF PORPHYRINS (PROTOPORPHYRIN IX)
brain, presenting with diffuse cerebral atrophy with dementia
• The characteristic senile plaques and neurofibrillary bundles
contain aggregates of the protein β-amyloid
• Apolipoprotein E has been implicated as a potential mediator of
this conformational transformation

Amyloid plaques & neurofibrillary tangles in Alzheimer disease are

aggregates of protein B-amyloid

Dr. Rubio
STRUCTURAL
ORGANIZATION OF
PROTEINS
https://qrs.ly/ybe037d

Structure of Porphyrin
From Self-Assessment and Review of Biochemistry, 2nd Edition
2.8 GLOBULAR PROTEINS • Porphyrin are cyclic compounds formed by the linkage of 4
GLOBULAR VS FIBROUS PROTEINS aromatic pyrrole rings by methenyl (methyne) bridges
GLOBULAR FIBROUS • Porphyrins are colored compounds that emit a strong red
PROTEIN PROTEIN fluorescence when illuminated by UV light after being dissolved
Elongated or needle- in strong acids or inorganic solvents
Shape Spherical
shaped • Porphyrins have a maximum characteristic electronic absorption
MINIMALLY spectrum of around 400 nm known as the Soret peak
Solubility MORE SOLUBLE
SOLUBLE • Porphyrins causes photosensitivity
General Has dynamic
Structural proteins STRUCTURE OF HEME

Function functions
• Hemoglobin
• Myoglobin • Collagen fibers
Examples • Albumin • Elastin fibers
• Globulin • Keratin • Heme is a
• Most enzymes metallo-
porphyrin
containing
iron

Structure of Heme

MYOGLOBIN
• Heme protein present in heart and skeletal muscle
• Functions:

o Reservoir of oxygen
o Oxygen carrier that increases the rate of transport of O2 within
the muscle cell
• Consists of a single polypeptide chain (monomeric)
• Following massive crush injury, myoglobin released from
damaged muscle fibers colors the urine dark red
(myoglobinuria)
• Myoglobin can be detected in plasma following a myocardial
infarction
CHARACTERISTICS MYOGLOBIN HEMOGLOBIN HEMOGLOBIN COMPONENTS
Structure 1 polypeptide only 4 polypeptides AFTER BIRTH
O2 Bound 1 O2 only 4 O2 • α2 - β 2
Sigmoidal Hemoglobin A (HbA) • binds more with 2,3-BPG
O2 Dissociation Hyperbolic
Shows • 95% of hemoglobin after birth
Curve Shows saturation
cooperativity • α2 -δ2
Main Purpose For O2 storage For O2 transport Hemoglobin A2 (HbA2)
• 1.5-3.5% of hemoglobin after birth
Heart and skeletal • α2 - γ 2
Where Found Red blood cells
muscle Hemoglobin F (HbF) • can be elevated in persons with sickle
Allosteric Effects Absent Present cell disease & beta-thalassemia

MNEMONICS BLOOD CELL FORMATION

YOUNG LIVER SYNTHESIZES BLOOD.
Yolk Sac à Liver, Spleen à Bone Marrow

GLYCATED HEMOGLOBIN (HbA1C)

• When blood glucose enters the erythrocytes, it glycates the ε-amino
group of lysine residues and the amino terminals of hemoglobin
• ↑ glycation of hemoglobin noted in patients with diabetes
mellitus due to ↑ glucose in blood
HbA1c allows us to determine the glycemic control of DM patients over the
past 3 months
Dr. Rubio
Comparison of Myoglobin and Hemoglobin O2 Dissociation Curve

CLINICAL CORRELATES
ALLOSTERIC FACTORS CARBOXYHEMOGLOBIN
• Factors whose interaction with one site of hemoglobin affects the • Form of hemoglobin bound to carbon monoxide in place of O2
binding of O2 to heme groups at other locations • Hb becomes “cherry pink” in color
• Effect may be positive or negative • CO has 200x greater affinity for Hgb than O2
• Factors that cause a shift to the RIGHT: • Treatment: 100% O2 therapy
o ↑ CO2 o ↑ 2,3 BPG Recall: carbon monoxide also inhibits complex IV of the electron transport chain.
o ↑ Acidity (↓pH) o ↑ Exercise
Dr. Rubio
o ↑ Temperature METHEMOGLOBIN
• Oxidized form of hemoglobin (Fe3+) that does not bind O2 as
readily, but has ↑ affinity for cyanide
• Methemoglobinemia
o Symptoms: anxiety, headache, and dyspnea,
o Signs: chocolate cyanosis, O2 saturation is at 85%
o Treatment:
§ Mild: oral methylene blue or ascorbic acid, both reducing agents
§ Acute massive, due to ingestion of chemicals: IV methylene blue
In methemoglobin, ferrous (Fe2+) becomes ferric (Fe3+)

Dr. Rubio
HEREDITARY SPHEROCYTOSIS

A: Shift to the right (P50 is increased) • Disorder characterized by an inherited (intrinsic) defect in the RBC
B: Shift to the left (P50 is decreased) membrane that renders the erythrocytes spheroidal, less deformable,

and vulnerable to splenic sequestration and destruction
MNEMONICS O2-HgB DISSOCIATION CURVE • Multiple mutations have been described: ankyrin (most
“CABET, do the RIGHT thing, LET GO” common), spectrin, band 4.1 and band 3
CO2, Acidosis, BPG (2,3 BPG), Exercise, Temperature • Clinical manifestations:
o Anemia, splenomegaly, jaundice
• Diagnosed: Osmotic fragility test
2,3-BISPHOSPHOGLYCERATE
• Treatment: No cure
• Stabilizes the T structure of hemoglobin by forming additional o Splenectomy for symptomatic patients
salt bridges that must be broken prior to conversion to the R state Splenectomy only provides symptomatic relief, since splenic infarcts may
• A low pO2 in peripheral tissues promotes the synthesis in cause pain. Spherocytes also hemolyze earlier in the circulation due to the
erythrocytes of 2,3-bisphosphoglycerate from the glycolytic absence of biconcavity which allows RBCs to squeeze through small vessels
intermediate 1,3-bisphosphoglycerate
Dr. Rubio
SICKLE CELL DISEASE
• Effects:
o In infants, 2,3-BPG binds weaker to HbF than to HbA. Hence, • Results from a point mutation (missense) in both genes coding
HbF has a higher affinity for O2 than HbA. for the β-chain that results in a change from glutamate → valine
o Prolonged exposure to high altitude increases the number of (at the 6th position)
erythrocytes. ↑hemoglobin and ↑ BPG lowers the affinity of HbA • Homozygous recessive disorder
for O2
BPG
https://qrs.ly/dge03ac

Adapted from Ferrier DR. Lippincott Illustrated Reviews: Biochemistry. 7th ed. 2017.
The change from glutamate → valine is significant because there is a
TYPES OF HEMOGLOBIN change from a charged amino acid → nonpolar amino acid
HEMOGLOBIN COMPONENTS
Dr. Rubio
IN THE EMBRYO • Effect on RBC:

Gower I hemoglobin • ζ2 - ε2 o Polymerization & decreased solubility of the deoxy form of Hb
in times of low oxygen tension → distortion of the RBC
Gower II hemoglobin • α2 - ε2
membrane → sickling of the RBCs → occlusion of capillaries
Hemoglobin Portland I • ζ2 - γ2
• Clinical Manifestations:
Hemoglobin Portland II • ζ2 - β2 o Anemia, tissue anoxia, painful crises
IN THE FETUS o Protective against malaria
• α2 - γ 2 • Treatment: hydration, analgesics, antibiotics if with infection,
Hemoglobin F (HbF)
• binds less with 2,3-BPG transfusions, hydroxyurea
Hydroxyurea causes increased production of hemoglobin F, which has • Physical manifestations appear only after birth
increased affinity to oxygen (which is what we want to prevent sickling) Symptoms only manifest at around 6 months of age because before then,
Dr. Rubio

you rely on fetal hemoglobin that doesn’t contain beta chains.

HEMOGLOBIN C DISEASE
Dr. Rubio

• Hemoglobin variant that has a single amino acid substitution in the 6th • Two alleles are responsible for the production of β-globin
position of the β-globin chain, in which glutamate → lysine o Both alleles are found in chromosome 11
• Patients homozygous for hemoglobin C present with mild o The number of missing alleles contributes to the overall
hemolytic anemia presentation of β-thalassemia

Hemoglobin C disease is benign compared to sickle cell disease because

the replacement of glutamate, lysine (lyCine), is also a charged amino
acid. In simpler terms, it is not so different from the original amino acid
(glutamate) at the 6th position, hence the presentation is mild.

Dr. Rubio
ALPHA THALASSEMIA
• Inadequate synthesis of α-chains
• Leads to anemia, accumulation of Hb Bart (γ4) and Hb H (β4),
and β-chain precipitation
• Symptoms appear at birth because α-chains are needed for HbF
and HbA 1 missing allele β-Thalassemia minor / trait (mild anemia)

2 missing β-Thalassemia major (moderate or severe
The name of the thalassemia tells you what is deficient. In alpha
thalassemia, you don’t have alpha chains. In beta thalassemia, beta
alleles anemia)
chains.

Dr. Rubio
2.9 FIBROUS PROTEINS
• Four alleles are responsible for the production of α-globin
o All four alleles are found in chromosome 16
COLLAGEN
o The number of missing alleles contributes to the overall • Most abundant protein in the body
presentation of α-thalassemia • A long stiff extracellular structure in which 3 polypeptides (α-
chains) each 1000 AA in length are wound around one another in
a triple helix
• At least 28 distinct types made up of over 30 distinct polypeptide
chains have been identified in human tissues
• Most common form is type I collagen

1 missing allele Silent carrier
2 missing alleles α-Thalassemia trait (mild anemia)
Hemoglobin H disease (moderate to severe
3 missing alleles anemia)
Contains Hb H (β4),
Hydrops fetalis (lethal in utero without Structure of Collagen
4 missing alleles transfusions)

(not in photo above) Hydrogen bonding stabilizes the 3-part structure of the collagen.
Contains Hb Bart (γ4)
Dr. Rubio

• Rich in glycine and proline
Hb Bart, which is made up of 4 gamma-globin chains, becomes
prominent when alpha- and beta-globin chains become deficient
o Gly: glycine

Dr. Rubio o X: proline (facilitates kinking)
BETA THALASSEMIA o Y: hydroxyproline or hydroxylysine
• Inadequate synthesis of β-chains • Formed in fibroblasts (or in the osteoblasts of bone and
• Leads to anemia, accumulation of Hb Barts and α-chain chondroblasts of cartilage)
precipitation

SYNTHESIS OF COLLAGEN
1. Synthesis of pre-procollagen in the rough endoplasmic

reticulum, and cleavage of the signal (pre) sequence
2. Hydroxylation of proline and lysine residues, which
requires vitamin C
3. Glycosylation (addition of galactose and glucose) to
hydroxylysine residues → Formation of triple helix
4. Exocytosis of procollagen from the cell into the
extracellular matrix
5. Proteolytic processing (cleavage of disulfide-rich
terminal regions of procollagen) → insoluble
tropocollagen
6. Cross-linking of tropocollagen fibers via copper-
containing lysyl oxidase → collagen fibrils
Synthesis of Collagen
From First Aid for the USMLE 2020, 30th Edition
DISEASES ASSOCIATED WITH COLLAGEN SYNTHESIS DYSTROPHIC EPIDERMOLYSIS BULLOSA (DEB)
• Problem in hydroxylation step • The skin breaks and blisters as a result of minor trauma
• Due to vitamin C deficiency • Dystrophic form is due to mutations affecting the structure of
Scurvy
• Discussed further in Vitamins & Minerals type VII collagen, which anchors the basal lamina to collagen
module fibrils in the dermis
• Problem in formation of triple helix step
Osteogenesis
• Discussed further in Clinical Correlates part of SCURVY
imperfecta
this module • Hydroxylation of collagen is a post-translational modification
• Problem in cross-linking step requiring ascorbic acid
• Due to deficiency in copper → dysfunction of • Vitamin C deficiency causes ↓ cross-linking of collagen fibers
Menkes
lysyl oxidase • Manifestations:
disease
• Discussed further in Clinical Correlates part of o Sore spongy gums, Loose teeth
this module o Poor wound healing
o Petechiae on skin and mucous membranes

SYNTHESIS OF MENKES DISEASE
COLLAGEN
• Characterized by kinky hair and growth retardation
https://qrs.ly/uke03ag
• Reflects a dietary deficiency of the copper required by lysyl
oxidase
TYPES OF COLLAGEN o Catalyzes a key step in formation of the covalent cross-links that
I Bone, skin, tendon, dentin, fascia, cornea, late wound repair strengthen collagen fibers
II Cartilage (including hyaline), vitreous body, nucleus pulposus
(Reticulin) Skin, blood vessels, uterus, fetal tissue,
III
granulation tissue (early wound repair)
TYPES OF COLLAGEN
IV Basement membrane or basal lamina https://qrs.ly/hde03al
Anchoring fibrils – found beneath the stratified
VII
squamous epithelium

MNEMONIC TYPES OF COLLAGEN ELASTIN
Type One is in bONE and tendONE. • Connective tissue protein with rubber-like properties, responsible
Type Two is in Car TWOlage. for extensibility and elastic recoil in tissues
Type Three has THREEticulin. • Found in tissues where elastic recoil is needed
Type Four is under the FLOOR (FOUR), which is your basement o Lungs, large arteries, elastic ligaments, vocal cords, ligamentum
flavum
EHLERS-DANLOS SYNDROME • Rich in proline and lysine, but contains little hydroxyproline and
• Group of inherited disorders characterized by: no hydroxylysine
o Hyperextensibility of the skin • Precursor tropoelastin is deposited into an irregular fibrillin
o Abnormal tissue fragility scaffold cross-linked by desmosine
o Increased joint mobility

CLASSICAL HYPERMOBILITY VASCULAR

Defect in types I Defect in type III Defect in type III
and V collagen collagen collagen
• Fragile blood
• Similar to vessels and organs
• Joint
hypermobility • small stature
hypermobility
subtype but • thin and
• skin
more severe skin translucent skin,
abnormalities
abnormalities easy bruising
• osteoarthritis
and less severe • Increased risk of From Lippincott Illustrated Reviews Biochemistry, 7th Edition
joint changes • severe pain
intracranial
MARFAN SYNDROME
aneurysms
Most common Most serious • Autosomal dominant connective tissue disorder
• Mutation in the fibrillin gene (chromosome 15)
OSTEOGENESIS IMPERFECTA • Triad of manifestations:
• Brittle bone disease o Skeletal changes: taller and thinner, arachnodactyly, long
• Mutation in collagen genes → problem in triple helix formation extremities
→ result to bones that easily bend and fracture o Aortic dilatation (70 to 80%) and dissection
• Most common form is autosomal dominant with abnormal o Upward & outward dislocation of the lens (ectopia lentis)

collagen type I Imagine a Marfan patient with long extremities raising their hands
• Manifestations: upward and outward! On the other hand, the lens displacement seen in
o Multiple fractures (need to rule out child abuse) homocystinuria is downward and inward! 8 ;
:
9
o Blue sclerae

Dr. Rubio
o Hearing loss α-1 ANTITRYPSIN DEFICIENCY

o Dental imperfections • α-1 antitrypsin inhibits proteolytic enzymes from hydrolyzing

and destroying proteins
ALPORT SYNDROME
• If there is ↓α-1 antitrypsin in the lungs, elastase destroys the
• Genetic disorders affecting the structure of type IV collagen alveolar walls, resulting to emphysema
fibers, the major collagen found in the basement membranes of • Patients can also manifest with liver disease (e.g., cirrhosis and
the renal glomeruli hepatocellular carcinoma)
• Manifestations:
Imagine elastase as if it were scissors that keep on cutting elastin. α-1

o Hematuria (main presenting sign)
antitrypsin prevents it from doing so.
o Ocular lesions
Dr. Rubio
o Hearing loss

o Patients may eventually develop end-stage renal disease

AlFOURth syndrome involves Type 4 collagen. The glomerular and cochlear
basement membranes are also affected.

Dr. Rubio
2.10 STRUCTURE OF IMMUNOGLOBULINS Mnemonic:

Pa-pa-in has 3 “syllables” = cleaves Ig into 3 parts
For an extensive discussion on immunology, please consult your Physiology Pep-sin has 2 syllables = cleaves Ig into 2 parts
and Pathology handouts. I will only discuss here the structure of
Dr. Rubio
immunoglobulins – a pertinent and testable concept in the PLE! <C
B
A
@
?
>
= IMPORTANT TERMINOLOGIES ASSOCIATED WITH
Dr. Rubio

IMMUNOGLOBULINS
IMMUNOGLOBULINS Refers to the part of the ANTIGEN to which an
Epitope
• Also known as antibodies antibody binds
• Synthesized mainly in plasma cells (specialized cells of B-cell Refers to the part of the ANTIBODY that binds to
Paratope
lineage) in response to exposure to a variety of antigens the epitope of the antigen
A macromolecule (often a peptide) which MIMICS
the structure of an epitope
Mimotope
It causes an antibody response similar to the one
elicited by the epitope

3. STRUCTURE OF CARBOHYDRATES
1. Overview of Carbohydrates
2. Classification of Carbohydrates
3. Projections, Properties, and Isomerism of Carbohydrates
4. Glucose Transporters

3.1 OVERVIEW OF CARBOHYDRATES
• Most abundant organic molecules in nature
• Empiric formula of Cn(H2O)n, where n = number of carbon
atoms
• Functions:
o Major energy source = glucose
Structure of Immunoglobulins o Storage form of energy = glycogen
From First Aid for the USME 2020, 30th Edition
o Component of cell membranes = glycoproteins
o Structural component in plants, bacteria, and insects
STRUCTURE OF IMMUNOGLOBULINS
• Consists of 2 heavy chains, and 2 light chains
• Both heavy and light chains are divided into constant and variable
3.2 CLASSIFICATION OF CARBOHYDRATES
regions: CLASSIFICATION NUMBER OF SUGAR UNITS
Constant region Towards the carboxyl end • One sugar unit
Monosaccharides
Variable end Towards the amino end • Building block of all carbohydrates
Disaccharides • Two sugar units
Fab & Fc REGIONS Oligosaccharides • 3 to 10 sugar units
Fab Fc Polysaccharides • More than 10 sugar units
Contains both light and Contains heavy chains The sugar units are linked together by glycosidic bonds.
heavy chains only
Structure SUBCLASSIFICATION OF MONOSACCHARIDES DEPENDING ON
Contains variable and Contains constant
constant regions region only THE NUMBER OF CARBON ATOMS
Site of complement & NUMBER OF CARBON
GENERIC NAME
Contains antigen- macrophage binding ATOMS
Function
binding site Determines the isotype 3 Trioses
(class) 4 Tetroses

Fab = contains antigen-binding site 5 Pentoses

Fc = contains complement-binding site 6 Hexoses

Dr. Rubio
7 Heptoses
HINGE REGION
9 Nonoses
• Region found between CH1 and CH2 domains

• Confers flexibility and allows both Fab arms to move
SUBCLASSIFICATION OF MONOSACCHARIDES BASED ON
independently → helping them to bind to antigenic sites
FUNCTIONAL GROUP

HEAVY CHAINS
• Immunoglobulins are divided into 5 classes (isotypes) based on
the heavy chain present
IgG Gamma-chain
IgA Alpha-chain
IgM Mu-chain
IgD Delta-chain
IgE Epsilon-chain
LIGHT CHAINS
• Consists of Kappa and Lambda chains
• Most abundant light chain in humans is Kappa chain

Kappa and/or lambda chains (light chains) are the main composition of
Bence-Jones proteins, which is seen in the urine of patients with multiple
myeloma

Dr. Rubio
PROTEOLYTIC CLEAVAGE OF IMMUNOGLOBULINS
• Cleaves the Ig into 3 parts:
Papain
o 2 separate Fab fragments ALDOSES VS KETOSES CLINICALLY IMPORTANT
digestion
o 1 Fc fragment https://qrs.ly/bje03b4 CARBOHYDRATES
• Cleaves the Ig into 2 parts: https://qrs.ly/h5e03b7
Pepsin
o 1 bivalent Fab fragment (combined Fab fragments)

digestion
o 1 Fc fragment

CLINICALLY IMPORTANT CARBOHYDRATES
CLASSIFICATION CARBOHYDRATE REMARKS
• Main metabolic fuel for brain, renal medulla, cornea, retina, testis, RBC
• Most predominant sugar in human body; universal fuel of fetus
Glucose
• Oxidation yields glucuronic acid
• Reduction yields sorbitol
Monosaccharides • Obtained from fruit juices
Fructose
(Hexoses) • Accumulates in fructose intolerance
• Obtained from lactose in dairy products
Galactose • Synthesized in the mammary glands
• Constituent of glycolipids and glycoproteins
Mannose • Constituent of glycoproteins
• Structural component of nucleic acids and coenzymes
Ribose
Monosaccharides • Removal of the hydroxyl group at C2 yields deoxyribose
(Pentoses) Ribulose • Intermediate in pentose phosphate pathway
Xylulose • Excreted in the urine in essential pentosuria
• Glucose + Fructose
Sucrose
• Sucrase deficiency leads to diarrhea and flatulence
• Glucose + Galactose
Disaccharides Lactose • Lactase deficiency leads to diarrhea and flatulence
• May be excreted in the urine in pregnancy
• Glucose + Glucose
Maltose
• Intermediate in the digestion of starch
• Storage polysaccharide in animals, made up of glucose
• Has α1→4 linkage at the linear part; α1→6 linkage at branches
Glycogen
Polysaccharides

Structure of Glycogen
• Storage polysaccharide in plants, made up of glucose
• Has 2 main constituents:
o Amylose (20%): non-branching helical structure
§ Soluble, unbranched
Starch
§ Has α1→4 linkage
o Amylopectin (80%): has branched chains w/ 24-30 glucose residues
§ Insoluble, branched
§ Has α1→4 linkage at the linear part; α1→6 linkage at branches
Cellulose • Chief constituent of plant cell walls
• Polysaccharide of fructose that is readily soluble in water and is used to determine glomerular
Inulin
filtration rate
• Found in exoskeleton of crustaceans, insects
Chitin
• Found in cell wall of fungi
3.3 PROJECTIONS, PROPERTIES, AND ISOMERISM

OF CARBOHYDRATES
PROJECTIONS OF CARBOHYDRATES
A: FISCHER PROJECTION
• Shows the linear structure

B: HAWORTH PROJECTION
• Shows the cyclic structure, as viewed from the side, showing the
stereochemistry or location of attached molecules to
monosaccharide ring

C: CHAIR CONFORMATION
• It is also possible to have a boat conformation in which C1 is tilted
Fischer Projection, Haworth Projection, and Chair Conformation of Glucose
upwards, in the same direction as C4 (less common) From Harper’s Illustrated Biochemistry. 30th ed. 2015
The most stable conformation of glucose is the chair conformation. In this
conformation the different constituents of glucose (especially the bulky
groups – OH, CH2OH) are not crowded – hence more stable

Dr. Rubio

REDUCING SUGARS
• Carbohydrates that can act as reducing agents because they have
a free functional group: aldehyde group or ketose group
• Can be identified using the Benedict’s test

• Glucose
Pyran and Furan Rings
• Galactose From Self-Assessment and Review of Biochemistry, 2nd Edition
Reducing
• Fructose
sugars
• Lactose
• Maltose
Non-reducing • Sucrose
sugar • Trehalose (sugar of insect hemolymph)

All the hexoses have a free functional group – hence they are reducing
sugars

Dr. Rubio
ISOMERS
• Compounds that have the same chemical formula
• Glucose, fructose, galactose, and mannose are all isomers of one
another because they have the same formula C6H12O6 (hexoses) From BRS Biochemistry, Molecular Biology and Genetics, 7th Edition

EPIMERS
STRUCTURE OF
• Isomers that differ in configuration around only one specific CARBOHYDRATES
carbon atom (except the carbonyl carbon: refers to the carbon https://qrs.ly/eacqpi6
atom double-bonded to an oxygen atom)

3.4 GLUCOSE TRANSPORTERS
• These transporters facilitate the entry of glucose into cells
• Among the transporters, only GLUT4 requires insulin
o Hence, in Type 1 diabetes mellitus (insulin deficiency), glucose is
unable to enter muscle and adipose tissue → hyperglycemia
because glucose remains in the blood
• All glucose transporters use facilitated diffusion, except for
2nd Epimer of Glucose Mannose
SGLT1/2 (uses secondary active transport)
3rd Epimer of Glucose Allose
4th Epimer of Glucose Galactose TRANSPORTER LOCATION FUNCTION(S)

The difference involves the orientation of H and OH group around the RBCs, brain,
involved carbon atoms! GLUT1 Glucose uptake
cornea, placenta
Dr. Rubio
β islet cells of

Rapid uptake or
ENANTIOMERS GLUT2 pancreas, liver,
release of glucose
kidney, GI tract
• Optical isomers or stereoisomers
GLUT 3 Brain, placenta Glucose uptake
• Pairs of structures that are mirror images of each other
Heart and skeletal
• The enantiomers are designated as a D-sugar (Dextrorotatory) Insulin-stimulated
GLUT 4 muscle, adipose
and an L-sugar (Levorotatory) glucose uptake
tissue
• D-sugars are more common Small intestine,
• Example: GLUT 5 Absorption of fructose
spermatocytes
o L-glyceraldehyde and D-glyceraldehyde Sodium-dependent
o L-glucose and D-glucose Kidneys, small active uptake of
SGLT1/SGLT2
intestine glucose against a
concentration gradient

In the small intestines, GLUT 2 is found in the basement membrane (2

words). GLUT5 is found in the lumen (5 letters). Moreover, fructose
serves as the source of energy for sperm motility, hence GLUT5 is
present in spermatocytes

Dr. Rubio

4. STRUCTURE OF LIPIDS
1. Definition of Lipids
2. Fatty Acids
Enantiomers 3. Classification of Lipids
From Harper’s Illustrated Biochemistry. 30th ed. 2015
4. Triacylglycerol
5. Structure of Lipoproteins
ANOMERS 6. Structure of Cholesterol
• In aqueous solutions, monosaccharides with five or more carbon
atoms in the backbone occur predominantly as cyclic (ring)
structures:
4.1 DEFINITION OF LIPIDS
Furanose Monosaccharide structure with a 5-membered ring • Lipids are heterogeneous group of compounds relatively
Pyranose Monosaccharide structure with a 6-membered ring insoluble in water and freely soluble in nonpolar organic
• Rotation around the carbonyl carbon produces anomers, which solvents (ether, chloroform)
are labeled α and β anomers • Unlike carbohydrates & proteins, lipids are not chemically
• Unlike epimers, anomers can undergo interconversion (from α to related, but are physically related (in terms of solubility to
nonpolar organic solvents)
β, and vice versa) without energy expenditure or the need for
enzymes, in a process called mutarotation • They are not true polymers, unlike carbohydrates & proteins

Review:
Carbohydrates: polymer of monosaccharides
Proteins: polymer of amino acids

Dr. Rubio
• Generally compartmentalized to “protect” themselves from
watery environment of cells
• Functions:
o Important constituent of diet
o Storage form of energy
o Provide thermal insulation
o Serve as electrical insulators of myelinated nerves

4.2 FATTY ACIDS
• Are carboxylic acids with a long aliphatic hydrocarbon chain
R = Aliphatic hydrocarbons (CH)
• The R group of fatty acids accounts for the nonpolar nature of fat

Saturation of Fatty Acids
From https://ib.bioninja.com.au/standard-level/topic-2-molecular-biology/23-carbohydrates-and-lipids/types-of-fatty-
acids.html

Red part (COOH) part is the polar head, then the rest is the nonpolar tail.
Palmitic acid and stearic acid are saturated fatty acids (no double bound)
Oleic acid is a monounsaturated fatty acid (one double bound). Double

Structure of a Fatty Acid bonds introduce kinks in the molecule.
From Lippincott Illustrated Reviews Biochemistry, 7th Edition
Dr. Rubio
NAMING FATTY ACIDS

Review:
Nonpolar: water-fearing, hydrophobic
Polar: water-loving, hydrophilic

Dr. Rubio
CLASSIFICATION OF FATTY ACIDS (FA)

• Fatty acids can be classified depending on chain length, presence
of double bonds, and the number of double bonds present (in
FATTY ACID NAMING
unsaturated fatty acid)
https://qrs.ly/mje03c4

DEPENDING ON THE CHAIN LENGTH IMPORTANT FATTY ACIDS

Short chain FA C2-C6 STRUCTURE
Medium chain FA C8-C14 FATTY ACID (# of double REMARKS
Long chain FA At least C16 bonds)
Very long chain FA At least C22 Predominant FA in coconut
Lauric acid 12 : 0
oil
✔INTEGRATION: PHYSIOLOGY End-product of mammalian
Palmitic acid 16 : 0
Significance of medium-chain fatty acids (MCFA) FA synthesis
• Absorbed directly into the blood (do not need to be transported to the Oleic acid 18 : 1 (9) Predominant FA in olive oil
lymphatic system via chylomicrons) – because MCFA are relatively Linoleic acid 18 : 2 (9, 12) Essential fatty acid
water soluble α-Linolenic 18 : 3
• Diet rich in MCFA may be of particular benefit in patients with Essential fatty acid
acid (9, 12, 15)
inadequate bile acid pools Precursor of eicosanoids
• Do not need carnitine for transport into mitochondria
Arachidonic 20 : 4 Semi-essential fatty acid –
• Has no effect on atherosclerosis
acid (5, 8, 11, 14) because it can be derived
Significance of small-chain fatty acids (SCFA)
• SCFA (acetate, butyrate, propionate) are produced by bacterial
from Linoleic acid

fermentation of dietary carbohydrates ESSENTIAL FATTY ACIDS

• Also absorbed directly into the blood • Fatty acids that are required by humans (since they are not
• Important source of energy for the colonic mucosa, and synthesized in the body)
metabolism by colonocytes provides energy for processes such as
active transport of sodium (Schwartz, Berne and Levy)
• Rationale: Humans lack the enzymes that can introduce double
bonds beyond the 9th carbon

DEPENDING ON THE PRESENCE OF DOUBLE BOND Linoleic acid

Essential FA
• NO DOUBLE BOND in the hydrocarbon chain α-Linolenic acid
Saturated Semi-essential FA Arachidonic acid
• FA is saturated with hydrogen!
FA
• Means that all C-C bonds are single bonds LinoleNic acid = Not the parent compound of arachidonic acid
Unsaturated • AT LEAST ONE DOUBLE BOND in the Linoleic acid = parent compound of arachidonic acid
Dr. Rubio
FA hydrocarbon chain is present
• Functions of essential fatty acids:

o Integral components of membrane structure
DEPENDING ON THE NUMBER OF DOUBLE BONDS PRESENT IN
o Needed for the synthesis of arachidonic acid (parent compound
UNSATURATED FATTY ACID
of the eicosanoids – prostaglandins, prostacyclin, leukotrienes,
Monounsaturated FA ONLY 1 DOUBLE BOND is present
thromboxane)
Polyunsaturated FA MORE THAN 1 DOUBLE BONDS are present o Lower the risk of cardiovascular disease
o Lower the risk of fatty liver disease
GEOMETRIC ISOMERISM OF FATTY ACIDS
Cis-form H atoms are found on the SAME SIDE OMEGA FATTY ACIDS
Trans-form H atoms are found on the OPPOSITE SIDE • Please watch the video prepared by Dr. Recuenco to appreciate
the omega nomenclature of fatty acids
• Depending on the position of the first double bond from the
terminal methyl end, fatty acids are classified as:
• α-Linolenic acid
ω-3
• Timnodonic acid (eicosa-pentaenoic acid)
series
• Cervonic acid (docosahexaenoic acid) (DHA)
ω-6 • Linoleic acid
series • Arachidonic acid
ω-9 • Oleic acid
series • Elaidic acid
• Significance of ω-3 FAs: You need lipoproteins and albumin to transport triglycerides and
o Decreases serum triglycerides → ↓ risk of cardiovascular fatty acids in the blood because these compounds are nonpolar.
disease Lipoprotein pertains to the whole structure. Apoprotein or apolipoprotein
pertains to just the protein component.
o Lowers the production of thromboxane → ↓ tendency for Dr. Rubio
platelet aggregation

Recall that thromboxane is a derivative of arachidonic acid, an ω-6 FA.

Increasing the intake of ω-3 FAs will decrease the relative concentration of
your ω-6 FAs

Dr. Rubio
o Lowers the production of thromboxane → ↓ tendency for
platelet aggregation
o Important for infant development – DHA

Are you familiar with the “DHA” branding of numerous infant formula
milks? DHA is synthesized from α-Linolenic acid. It is needed for the
development of fetal brain and retina.

Dr. Rubio

FATTY ACIDS
https://qrs.ly/cje03c9

Adapted from Harper’s Illustrated Biochemistry, 30th Edition
IMPORTANT LIPOPROTEINS
LIPOPROTEIN SOURCE PROTEIN LIPID REMARKS
Largest diameter,
98– Lowest density,
4.3 CLASSIFICATION OF LIPIDS Chylomicron Intestine 1–2%
99% Highest
SIMPLE COMPLEX PRECURSOR AND DERIVED TAG content
LIPIDS LIPIDS LIPIDS 90–
VLDL Liver 7–10% -
93%
• Fats • Phospholipids • Fatty acids
IDL VLDL 11% 89% -
• Oils • Glycolipids • Glycerol Highest
• Waxes • Lipoproteins • Steroids LDL VLDL 21% 79% cholesterol
• Sulfolipids • Ketone bodies content
• Aminolipids • Hormones HDL
Liver
32–57%
43– Highest protein
• Fat-soluble vitamins and Intestine 68% content
micronutrients Note: Free fatty acids or non-esterified fatty acids are transported in the
plasma bound to albumin, with low levels during the well-fed state, but which
subsequently rise in the fasted state.
SIMPLE LIPIDS
As you increase the protein content of lipoproteins (thereby lowering the

• Are esters of fatty acid + alcohol lipid content), the density also increases. And vice versa.

Dr. Rubio
Simple lipids = Fatty acid + Glycerol

Fats Solid at room temperature SUMMARY OF APOLIPOPROTEINS
Oils Liquid at room temperature APO- FOUND
FUNCTIONS
PROTEIN MAINLY IN
COMPLEX LIPIDS Cofactor of LCAT (lecithin:
Apo
• Are (esters of fatty acid + alcohol) + additional groups HDL cholesterol acyltransferase)
A-1
• Additional groups can be phosphoric acid, carbohydrates, proteins Structural component of HDL

Mediates assembly and
Complex Lipids = Fatty acid + Glycerol/Sphingosine + Apo secretion of VLDL
Additional groups VLDL, IDL, LDL
B-100 Structural protein of VLDL,
IDL, LDL
4.4 TRIACYLGLYCEROL Apo
Main apoprotein and mediates
• Formed by linking fatty acids with an ester linkage to 3 alcohol Chylomicrons secretion of chylomicrons from
B-48
groups in glycerol: small intestines

Chylomicrons,
Triacylglycerol = 3 Fatty acids + Glycerol Apo C-II* Cofactor of lipoprotein lipase
VLDL IDL, HDL
Chylomicron Mediates uptake of
• Main storage form of lipids in the Apo E* remnants, chylomicron remnants and
body – stored in the adipose tissues VLDL, IDL, HDL IDLs

• Also known as triglyceride, neutral fat

APOLIPOPROTEINS
https://qrs.ly/5ve03ca
Structure of Triacylglycerol

For an overview of apolipoproteins, please take time and watch the video
4.5 STRUCTURE OF LIPOPROTEINS prepared by Dr. Recuenco, one of our lecturers in Biochemistry!
PLASMA LIPOPROTEINS Lipid transport will be discussed further by Dr. Baticulon. Stay tuned! .
1
0
/
• Spherical macromolecular complexes of lipids + proteins called
Dr. Rubio

apolipoproteins (or apoproteins)

CLINICAL CORRELATE
Lipoprotein = Lipids + Apolipoproteins ATHEROSCLEROSIS

• Structure: • Deposition of cholesterol and cholesteryl esters in the artery

o Core: Neutral lipids walls especially from oxidized LDL
o Shell: Amphipathic apolipoproteins, phospholipid, and free • Oxidized LDLs cause endothelial damage which predisposes to
fatty acids atherosclerosis
• Functions: • More severe in diabetes mellitus, lipid nephrosis, hypothyroidism
o Keep lipids soluble in plasma
o Provide an efficient transport mechanism for lipids to and from
various tissues
4.6 STRUCTURE OF CHOLESTEROL CHOLESTEROL

• An important steroid in animal tissues
o Adults normally synthesize approximately 1 g and consume
about 0.3 g per day
o Stored as cholesteryl esters (cholesterol + fatty acid chain)

Note that the hydroxyl (OH) group is in the A ring and the hydrocarbon tail
is in the D ring.

Dr. Rubio
• Structure:
o 27-carbon compound
o Steroid nucleus: four fused hydrocarbon rings (A-D)
o An eight-carbon, branched hydrocarbon chain attached to
Structure of Cholesterol
Adapted from Lippincott Illustrated Reviews Biochemistry, 7th edition carbon 17 of the D ring
o Hydroxyl group at carbon 3 of the A ring
o Double bond between carbon 5 and 6 of the B ring
DERIVATIVES OF CHOLESTEROL
ENZYME PRODUCTS
• Primary bile acids: bile acids synthesized by the liver
o Cholic acid
7α-hydroxylase
o Chenodeoxycholic acid
Cholesterol →
• Secondary bile acids: bile acids resulting from bacterial degradation in the colon
Bile acids 7α-hydroxy-cholesterol
o Deoxycholic acid (from cholic acid)
(rate-limiting step in bile
o Lithocholic acid (from chenodeoxycholic acid)
acid synthesis)
• Bile salts
o Conjugated to taurine and glycine (e.g., taurocholic acid, glycocholic acid)
• Glucocorticoids (Cortisol)
Adrenal hormones Desmolase
• Mineralocorticoids (Aldosterone)
Cholesterol →
Pregnenolone • Testosterone
Sex hormones
• Estradiol
Vitamin D • 7-dehydrocholesterol

Primary bile acids begin with the letter C. Bile salts have the prefix glyco- or tauro- because they are attached to glycine or taurine. Steroid hormones are derived
from cholesterol. Cortisol prevents hypoglycemia during stress. Glucagon prevents hypoglycemia during fasting. Aromatase converts androgens to estrogens.

Dr. Rubio
BILE ACIDS
https://qrs.ly/uke03ce

5. STRUCTURE OF NUCLEOTIDES

1. Components of Nucleotides
2. Nucleic Acids
3. Structure and Organization of DNA
4. Overview of RNA

5.1 COMPONENTS OF NUCLEOTIDES
• The components of nucleotides are:

Nucleotide = (𝐍𝐢𝐭𝐫𝐨𝐠𝐞𝐧𝐨𝐮𝐬 𝐛𝐚𝐬𝐞 + 𝐏𝐞𝐧𝐭𝐨𝐬𝐞 𝐬𝐮𝐠𝐚𝐫) +

𝐏𝐡𝐨𝐬𝐩𝐡𝐚𝐭𝐞

Purines and Pyrimidines found in DNA & RNA
Nucleoside = Nitrogenous base + Pentose sugar From Lippincott Illustrated Reviews Biochemistry, 7th Edition

NucleoSide = base + Sugar Remember:
NucleoTide = base + sugar + phosphaTe Adenine, Guanine = present in both DNA & RNA
Dr. Rubio

Cytosine = present in both DNA & RNA

NITROGENOUS BASE Uracil = present only in RNA
• Refers to nitrogen-containing heterocyclic ring structures Thymine = present only in DNA
• 2 types of nitrogenous bases: Purine & Pyrimidine

Dr. Rubio
STRUCTURE OF THE PURINE RING
• Adenine • Seen below are the sources of the individual atoms in the purine
• Guanine ring; the order in which the atoms are added is shown by the
Purine • Xanthine, Hypoxanthine (not seen numbers in the black boxes:
in RNA & DNA but are important

molecules in purine metabolism)

• Cytosine
Pyrimidine • Uracil
• Thymine

PuGA = Purines, Guanine & Adenine (are seen in DNA and RNA)
CUT the PY (Pie) = Pyrimidines, Cytosine, Uracil, Thymine

Dr. Rubio

Sources of the Individual Atoms in the Purine Ring
From Lippincott Illustrated Reviews Biochemistry, 7th Edition

STRUCTURE OF THE PYRIMIDINE RING NOMENCLATURE OF NUCLEOSIDES & NUCLEOTIDES
• Seen below are the sources of the individual atoms in the PENTOSE NUCLEOTIDE
BASE NUCLEOSIDE
pyrimidine ring: SUGAR (+ 1 PO4)
Ribonucleosides, Ribonucleotides
Adenosine
Adenine Ribose Adenosine
monophosphate
Guanosine
Guanine Ribose Guanosine
monophosphate
Cytidine
Cytosine Ribose Cytidine
monophosphate
Uridine
Uracil Ribose Uridine
monophosphate
Inosine
Hypoxanthine Ribose Inosine
Sources of the Individual Atoms in the Pyrimidine Ring monophosphate
From Lippincott Illustrated Reviews Biochemistry, 7th Edition Xanthosine
Xanthine Ribose Xanthosine
monophosphate
The sources of the atoms of the purine & pyrimidine rings are testable
questions. As a tip, the best way to memorize this is to draw them while Deoxyribonucleosides, Deoxyribonucleotides
reviewing this handout 8 ;
:
9 dAdenosine
Adenine Deoxyribose dAdenosine

Dr. Rubio monophosphate
PENTOSE SUGAR Guanine Deoxyribose dGuanosine
dGuanosine
• There are 2 types of pentose sugar: monophosphate
dCytidine
Cytosine Deoxyribose dCytidine
RNA D-Ribose sugar (ribose) monophosphate
DNA 2’-deoxy D-Ribose sugar (deoxyribose) Thymidine
Thymine Deoxyribose dThymidine
monophosphate
Note: d = deoxy
NUCLEOSIDE
Familiarize yourself with the “language of the nucleotides”. “Parang love

• Refers to the combination of nitrogenous base & pentose sugar
lang ‘yan.” If you know your and your partner’s love language, “swabeng-
• N-glycosidic linkage: serves as the bond between the base and swabe”
sugar (nucleosides are N-glycosides)
Dr. Rubio

Nucleoside = Nitrogenous base + Pentose sugar 5.2 NUCLEIC ACIDS
• Nucleic acids are polymers of nucleotides joined by a 3’-5’
phosphodiester bond
NUCLEOTIDE • There are 2 types of nucleic acids:
• Refers to the combination of nucleoside + phosphate o Deoxyribonucleic acid (DNA)
• Ester bond: serves as the bond between the 5’-OH of pentose o Ribonucleic acid (RNA)
sugar and phosphoryl group • Polyfunctional acids

• Negatively charged at physiologic pH
Nucleotide = (𝐍𝐢𝐭𝐫𝐨𝐠𝐞𝐧𝐨𝐮𝐬 𝐛𝐚𝐬𝐞 + 𝐏𝐞𝐧𝐭𝐨𝐬𝐞 𝐬𝐮𝐠𝐚𝐫) + General
• Absorbs UV light at wavelength 260 nm at pH
properties
𝐏𝐡𝐨𝐬𝐩𝐡𝐚𝐭𝐞 7.0 (due to the conjugated double bond of purine

and pyrimidine nucleotide)
OR

3’-5’ • 3’-hydroxyl (-OH) of sugar of 1st
Nucleotide = Nitrogenous base ← N-glycosidic linkage → phosphodiester mononucleotide is linked to 5’-phosphoryl
bond (PO32-) of 2nd mononucleotide
Pentose sugar ← Ester bond → Phosphate
Writing the base

• Written from 5’ end → 3’ end (see below)
sequence
Anhydride bond:
additional
phosphoryl groups
are attached by an
acid anhydride
bond to form
nucleoside
diphosphates and
triphosphates
Nucleic Acid

Ribonucleoside monophosphate, COMPARISON OF DNA AND RNA
Ribonucleoside diphosphate, Ribonucleoside
triphosphate DNA RNA
From Lippincott Illustrated Reviews Biochemistry, 7th Edition Mostly seen in NUCLEUS Mostly seen in CYTOPLASM

Pyrimidine bases: Pyrimidine base:
FUNCTIONS OF NUCLEOTIDES THYMINE, CYTOSINE URACIL, CYTOSINE
• Building blocks of nucleic acid Sugar: DEOXYRIBOSE Sugar: RIBOSE
• Other functions of nucleotides: Usually DOUBLE-STRANDED SINGLE-STRANDED
o Carriers of activated intermediates in the synthesis of
carbohydrates, lipids, and conjugated proteins
o Structural component of coenzymes
5.3 STRUCTURE AND ORGANIZATION OF DNA
o Second messengers in signal transduction pathways HISTORY
o Principal biologic transducer of free energy • James Watson, Francis Crick, Rosalind Franklin
o Regulatory compounds of pathways in intermediary o Three scientist who worked together on studying the structure
metabolism of DNA
o Synthetic analogs are used as drugs o The proposed model was based on the X-ray diffraction
ATP Most abundant free nucleotide in mammalian cell photographs of DNA taken by Rosalind Franklin
o Watson and Crick won a Nobel Prize in 1962 for their discovery

Trivia: Despite the efforts of Franklin, she will never win a Nobel Prize ORGANIZATION OF DNA
because she had died of ovarian cancer in 1958 and the Nobel committee
does not consider posthumous candidacies D H

G
F
E

Dr. Rubio

SALIENT FEATURES OF THE WATSON-CRICK DNA MODEL
COMPOSITION
• Right-handed (clockwise) double-stranded DNA helix

“Right-handed” means that the DNA strands turn clockwise when viewed
along its axis

Dr. Rubio
BASE PAIRING RULE
• Adenine (A) always pairs with Thymine (T) [Uracil (U) in RNA]
• Guanine (G) always pairs with Cytosine (C)

GC (grade-conscious) couples flock AT the library! SANA ALL! &

-
,
+
*
)
(
'

Dr. Rubio
HYDROGEN BONDING
G-C bonding 3 hydrogen bonds
A-T bonding 2 hydrogen bonds Structural Organization of DNA

From First Aid for the USMLE, 30th edition
GC couples are STRONGER TOGETHER because they help each other out HISTONES
to have high grades (hence 3 hydrogen bonds are formed)

Dr. Rubio • Most abundant chromatin
• G-C bonding is STRONGER than A-T bonding protein
o The higher the G-C content of a DNA, the higher the melting • Small family of closely related
temperature of DNA basic proteins (rich in arginine,
lysine)
ORIENTATION OF THE TWO STRANDS • Histones are divided into 2
• The 2 strands are antiparallel: types: core histones, linker
o One strand runs in 5’→3’ direction histones
o Other strand runs in 3’→5’ direction
Composition of Histone Octomer
From https://upload.wikimedia.org/wikipedia/commons/
GROOVES OF THE DNA a/a9/Basic_units_of_chromatin_structure.svg
• There are 2 types of grooves: major groove, minor groove • Composed of pairs of : H2A, H2B, H3, H4
• Grooves often acts as sites of DNA-protein interaction needed for • They form a histone octomer (see below)
Core histones
regulation of gene expression • H3, H4: rich in lysine
o DNA-protein interaction is via hydrophobic interaction & ionic bonding • H2A, H2B: rich in arginine
• H1 is seen in linker region
Linker histones
• Loosely bound to the nucleosome

The nonhistone proteins in chromatin include enzymes involved in DNA

replication and repair, RNA synthesis and processing. Negative charge in
DNA is due to phosphate groups; lysine and arginine give histones a
positive charge. This allows interaction between histones and DNA.

Dr. Rubio

LEVELS OF DNA ORGANIZATION

• DNA double helix
• 10 nm chromatin fibril
• 30 nm chromatin fibril
• Supercoiled structure
• Chromosome
• First level of organization of DNA
2 nm DNA
double helix

• Consists of nucleosomes separated by
linker DNA

Watson-Crick Model of DNA • DNA is wrapped 1.75 times (nearly twice)

10 nm over a histone octamer in left-handed helix
CHARGAFF’S RULE chromatin
• States that the number of purines = number of pyrimidines fibril
(beads on a
TYPES OF DNA string
• There are different types of DNA appearance on
• 6 types have been identified – A, B, C, D, E and Z, but the 3 more electron
prominent types are A, B, and Z microscopy)
• All types of DNA are right-handed, except Z (left-handed)

A-DNA B-DNA Z-DNA

Number of
base pairs 11 10 12 • Group of nucleosomes
per turns 30 nm
Broad and Longer and Longer and chromatin
Morphology
short thinner thinner fibril
Right- (solenoid)
Screw sense Right-handed Left-handed
handed
Found in low
Most common Supercoiled • Promotes packing of DNA into compact
humidity and Seen in 5’ end of
Features form
high salt chromosomes structure structures (see image above)
physiologically
conditions
• Condensation of DNA occurring during In general, the lncRNA, siRNA, miRNA, snRNA are all responsible for
prophase of mitosis regulation of gene expression
Dr. Rubio
• 23 pairs of chromosomes

Chromosome
(46 chromosomes in total)
o 22 pairs of autosomes
TYPES OF RNA
o 1 pair of sex chromosomes (X, Y)
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6. NUTRITION
1. Overview of Nutritional Assessment
2. Anthropometric Assessment
3. Dietary Assessment
4. Breastfeeding

6.1 OVERVIEW OF NUTRITIONAL ASSESSMENT
DEFINITION OF TERMS
Karyotype
From First Aid for the USMLE 2020, 30th Edition Refers to the science of foods and the
substances they contain – their actions,
Nutrition
EUCHROMATIN VS HETEROCHROMATIN interaction, and balance in relation to health
and disease
Nutritional Refers to the condition of the body resulting
Status from ingestion & utilization of nutrients
Refers to either nutrient deficiencies
Euchromatin (E),
Heterochromatin (H), Malnutrition (undernutrition) or nutrient excesses
Nucleolus (Nu) (overnutrition)
From First Aid for the Refer to constituents of food necessary to
USMLE 2020, 30th Edition Nutrients
sustain the normal functions of the body
Refers to the interpretation of information
obtained from anthropometric, biochemical,
Nutritional
clinical, and dietary studies to determine the
Status
EUCHROMATIN HETEROCHROMATIN health status of an individual as influenced by
Assessment
Less condensed Highly Condensed the intake and utilization of nutrients
Transcriptionally active First step in the treatment of malnutrition
Transcriptionally inactive
(Euchromatin is Expressed)
Stains less densely Stains densely METHODS IN NUTRITIONAL STATUS ASSESSMENT
(as seen above) (as seen above) • There are 4 main methods that can be used to collect information
needed to assess the nutritional status of the patient:
o Anthropometric assessment
5.4 OVERVIEW OF RNA o Biochemical assessment
This part of the module will be discussed extensively by Dr. Baticulon! For o Clinical assessment
now, let’s have an overview of the different types of RNA.
Dr. Rubio o Dietary assessment

TWO MAJOR CLASSES OF RNA Biochemical & clinical assessment of nutrition are discussed in various
Protein-coding RNA • mRNA subjects of the PLE (Pathology, Internal Medicine, Pediatrics,
Biochemistry). Hence, we are going to focus on the anthropometric &
• rRNA
dietary methods of assessing nutritional status in this section of the
• tRNA handout.
Nonprotein-coding
• snRNA Dr. Rubio
RNA

• miRNA/siRNA
• lncRNA 6.2 ANTHROPOMETRIC ASSESSMENT
ANTHROPOMETRIC ASSESSMENT
TYPES OF RNA • Refers to the measurement of the variations of the physical
• Most heterogeneous RNA dimensions and gross composition of the human body at different
Messenger RNA • Functions as messenger conveying age levels & degrees of nutrition
(mRNA) information from DNA to the
translation machinery (ribosomes) GROWTH FAILURE IN CHILDREN ASSOCIATED WITH
• Most abundant RNA (80% of total MALNUTRITION
Ribosomal RNA RNA) • There are 2 types of growth failure associated with malnutrition:
(rRNA) • Responsible for translation stunting and wasting
(formation of proteins)
• RNA which transfers amino acids WASTING STUNTING

from the cytoplasm to the Definition Refers to thinness Refers to shortness
ribosomes during translation Form of Reflects acute Reflects chronic
Transfer RNA malnutrition malnutrition malnutrition
• Contains significant proportions of
(tRNA) Best Weight-for-
nucleosides w/ unusual bases: Height/length-for-age
dihydrouridine, pseudouridine, indicator height/length

inosine, ribothymidine We use length up to children aged 2 years. Beyond that, we use height
• Has functions for gene already! If a child has stunted growth, it means that the problem is already
Small nuclear RNA expression regulation chronic to the point that there are already problems concerning skeletal
growth and maturation < C
B
A
@
?
>
=
(snRNA) o mRNA processing Dr. Rubio
o rRNA processing

Micro RNA (miRNA), • Responsible for gene expression
Small interfering regulation by targeting mRNA
RNA (siRNA) with several distinct mechanisms
Long noncoding RNA • Modulation of gene expression in
(lncRNA) many different mechanisms

PROTEIN-ENERGY MALNUTRITION ASIAN BMI CLASSIFICATION
• There are 2 types of severe acute malnutrition (SAM) which are BMI (kg/m2) NUTRITIONAL STATUS
defined based on whether caloric deprivation or protein Below 18.5 Underweight
deprivation is the major cause: 18.5 – 22.9 Normal weight
23.0 – 24.9 Overweight
25.0 – 29.9 Obese Class I
Above 30.0 Obese Class II

METHODS FOR BODY FAT MEASUREMENT
• Many of these methods can be difficult to standardize across
observers or machines, complicating comparisons across studies
and time periods
• Include the following: skinfold thickness measurements (w/
calipers), underwater weighing, bioelectric impedance, dual-
energy X-ray absorptiometry (DXA), isotope dilution
• These abovementioned methods are not always readily available,
expensive, or need to be conducted by highly trained personnel

METHODS FOR ABDOMINAL OBESITY MEASUREMENT
• Abdominal obesity: a strong predisposing factor for
(A) Kwashiorkor; (B) Marasmus cardiovascular disease (CVD)
From First Aid for the USMLE 2020, 30th Edition • The 2 most common methods for measuring abdominal obesity

MARASMUS KWASHIORKOR are: waist circumference & waist-hip ratio (WHR)

Caloric Protein deprivation > caloric o Waist circumference: measured at midpoint between the top
Cause of the iliac crest and the lower margin of the last palpable rib in
deprivation deprivation
• Edema (due to ↓ plasma the midaxillary line
oncotic pressure due ↓ o Hip circumference: measured at the largest circumference of
proteins) the buttocks
• Generalized • Small child w/ swollen • Waist circumference is favored over WHR due to the relative
Salient muscle abdomen ease of obtaining waist circumference.
features wasting • Fatty liver (↓ amino acid pool
• No edema → ↓ apolipoproteins) ETHNIC-SPECIFIC CUTPOINT VALUES FOR WAIST
• Hyperpigmented, CIRCUMFERENCE (ABDOMINAL OBESITY)
dyspigmented skin (flaky Men: >102 cm
WHO Classic definition
paint appearance) Women: >88 cm

Europeans
Marasmus = Muscle wasting; Kwashiorkor results from protein-deficient Sub-Saharan Africans Men: >94 cm
MEALS: Malnutrition, Edema, Anemia, Liver (fatty), Skin lesions
(hyperkeratosis, dyspigmentation)
Eastern Mediterranean Women: >80 cm

Dr. Rubio Middle Eastern
BODY MASS INDEX (BMI) South Asians
Men: >90 cm
Please do not ignore this section on BMI. Trends these days tend to include Chinese
Women: >80 cm
T/F questions (with EXCEPT) re: BMI J M
L
K Ethnic South & Central Americans
Dr. Rubio

Men: >85 cm
• Refers to the patient’s weight in kg divided by the square of the Japanese
Women: >90 cm
height in meters:

𝐖𝐞𝐢𝐠𝐡𝐭 𝐢𝐧 𝐤𝐠 WHO WAIST-HIP RATIO CUT-OFFS
Body Mass Index (BMI) = • According to WHO, abdominal obesity is defined when the WHR
(𝐇𝐞𝐢𝐠𝐡𝐭 𝐢𝐧 𝐦)𝟐

ratio is:
• Inexpensive and easy screening method for weight categorization Men >0.90
• BMI does not measure body fat directly Women >0.85
• BMI is strongly correlated with various metabolic and disease
outcomes 6.3 DIETARY ASSESSMENT
DIETARY REFERENCE INTAKES (DRI)
BMI AS AN INDICATOR OF BODY FATNESS
• Refer to the general term for a set of reference values used to plan
• General trends seen in BMI:
and assess nutrient intakes of healthy people
• Women tend to have more body fat than men • The DRI consists of 4 dietary reference standards for the intake of
• Blacks have less body fat than do Whites nutrients designated for a specific age group, physiologic state
• Asians have more body fat than do Whites & sex:
At the
same BMI: • Older people tend to have more body fat than
younger adults Estimated Average Requirement
• Athletes have less body fat than do non-
athletes Dietary
• Athletes may have a high BMI because of increased muscularity Recommended Dietary Allowance
Reference
rather than increased body fatness
Intakes (DRI)
Adequate Intake
WHO BMI CLASSIFICATION
BMI (kg/m2) NUTRITIONAL STATUS Tolerable Upper Intake Level
Below 18.5 Underweight
18.5 – 24.9 Normal weight • Average daily nutrient intake estimated to
25.0 – 29.9 Overweight meet the requirement of 50% of the
30.0 – 34.9 Obese Class I Estimated healthy individuals in a particular life
35.0 – 39.9 Obese Class II average stage and sex group
Above 40.0 Obese Class III requirement • Serves as the foundation for setting the
(EAR) RDA (see formula below)
• Useful in estimating the actual
requirements in groups & individuals
• Average daily nutrient intake level that is • Vitamin K
sufficient to meet the requirements of • Pantothenic acid
Recommended nearly all (97-98%) individuals in a • Biotin
dietary particular life stage and sex group • Choline
allowance • It is not the minimal requirement for
The table above is only a NICE TO KNOW CONCEPT. My point of including

(RDA) healthy individuals, but it is intentionally this is to show you that when EAR & RDA are not given for a specific
set to provide a margin of safety for most nutrient, an AI will be set (Review definitions of the DRI components above)
individuals
Dr. Rubio

• Most are set by age and sex, and may be influenced by special
RDA = 𝐄𝐀𝐑 + 𝟐𝐒𝐃𝐄𝐀𝐑 factors, such as pregnancy and lactation in women

• Because the DRI is designated to meet the nutritional needs of the
• An AI is set instead of an RDA if sufficient healthy, it DOES NOT include any special needs of the sick
Adequate • Interpretation of nutrient intake in association with DRI values:
scientific evidence is not available to
intake (AI)
calculate an EAR or RDA NUTRIENT INTAKE INTERPRETATION
• Refers to the highest average daily nutrient Need to be improved because the
Tolerable intake level that is likely to pose no risk of Intakes below EAR
probability of adequacy is ≤50%
upper adverse health effects to almost all Intakes between Likely need to be improved because the
intake level individuals in the general population EAR and RDA probability of adequacy is <98%
(TUL, or UL) • As intake increases above the UL, the Intakes at or above
potential risk of adverse effects may increase Considered adequate
RDA
Intakes above the
USING THE DIETARY REFERENCE INTAKES Considered adequate
AI
• Most nutrients have a set of DRI – usually a nutrient has an EAR Intakes between Can be considered to have no risk for
and corresponding RD, EXCEPT FOR THE FOLLOWING: RDA or AI, and UL adverse effects

Nutrients without • Manganese

EAR, RDA (these • Fluoride
have AI, instead) • Chromium

Relationship of the components of Dietary Reference Intakes (DRI)
ENERGY REQUIREMENT • Refers to the energy expended by an individual
• Estimated Energy Requirement (EER): refers to the average RMR in a resting, postabsorptive state
dietary energy intake predicted to maintain an energy balance in (60-75% of • Represents the energy required to carry out
a healthy adult of a defined age, sex, and height whose weight and TEE) normal body functions – respiration, blood flow
level of physical activity are consistent with good health & ion transport
• Achieving an energy balance (i.e. to maintain a body weight): Physical • Refers to the energy consumed depending on the
CALORIES CONSUMED = ENERGY EXPENDED activity duration & intensity of the exercise
• Simple approximations of energy requirement to maintain body (15-30% of
TEE) • It provides the greatest variation in the TEE
weight:
Sedentary adult 30 kcal/kg/day Thermic • The production of heat by the body increases as
Moderately active adults 35 kcal/kg/day effect of much as 30% above the resting level during
Very active adults 40 kcal/kg/day food digestion & absorption of food
(5-10% of
TEE) • Also known as diet-induced thermogenesis
ENERGY CONTENT OF FOOD
• Energy content of food is calculated from the heat released by the RESTING METABOLIC RATE VS. BASAL METABOLIC RATE
total combustion of food in a calorimeter • RMR and basal metabolic rate (BMR) are usually used
• It is expressed in kilocalories (kcal or Cal or food calorie) interchangeably, but these related parameters are still different:
o 1 kcal = 4.2 kJ
RMR BMR
Carbohydrates 4 kcal/g Parameters used to estimate the amount of calories a person
Protein 4 kcal/g will burn if her is at rest for 24 hours
Fat 9 kcal/g
Alcohol 7 kcal/g RMR BMR
Conducted in Conducted in
USE OF FOOD ENERGY IN THE BODY LESS RESTRICTIVE MORE RESTRICTIVE
• The energy generated by the metabolism of the macronutrients is conditions conditions
used for 3 energy-requiring process occurring in the body: Requires 8 hours of sleep in a
No requirement
(1) Resting metabolic rate (RMR) darkened room before testing
(2) Physical activity Requires 12 hours of fasting
(3) Thermic effect of food No requirement
before testing
• The number of kcal expended by these processes in a 24-hour More accurate and more
period is defined as total energy expenditure (TEE) 10% higher than BMR preferred by physicians, but
harder to conduct

o The influence of TAG on blood lipids is determined by the
chemical nature of their constituent fatty acids
§ Absence or presence of double bonds (saturated vs
unsaturated)
§ Number of double bonds (monounsaturated vs
polyunsaturated)
§ Location of double bonds (ω-6 vs ω-3)
§ Configuration of unsaturated fatty acids (cis vs trans)

Distribution of Total Energy Expenditure (TEE) BOTTOMLINE:
COMPUTATION OF THE RMR AND TEE increasing the
amount of LDL (bad
• The two widely used formulas for determining resting metabolic cholesterol) would
rate (RMR) (which is used to compute for the TEE) are: increase the incidence
o Harris-Benedict Equation (HBE) of coronary artery
o Mifflin-St. Jeor Equation (MSJE) disease. Increasing the

amount of HDL (good
Formula for MSJE: cholesterol) would
Females: RMR = 10W + 6.25H – 5A – 161 decrease the incidence
Males: RMR = 10W + 6.25H + 5A + 5 of coronary artery
Formula for HBE: disease. Among the
Females: RMR = 655.1 + 9.6W + 1.9H – 4.7A types of dietary fatty
Males: RMR = 66.5 + 13.8W + 5.0H – 6.8A acids, saturated fatty
acids & trans fatty
Where: RMR is resting metabolic rate; W is actual weight in kilograms; H
acids can increase the
is height in centimeters, and A is age in years

risk of coronary
I do not recommend memorizing the formulas above. Save it for other artery disease.
pieces of information. However, I would recommend that you familiarize Dr.
Structures of Trans Fatty Acid & Cis Fatty Acid

Rubio
the parameters used in computing the RMR! They are very testable!

From Lippincott Illustrated Reviews Biochemistry, 7 Edition

th

Dr. Rubio
• Composed of fatty acids whose hydrocarbon

• To compute for the TEE, we multiply the RMR by the

chains do not contain any double bonds
activity/stress factors below:
Saturated • Increases LDL, Decreases HDL
TEE = 𝐑𝐌𝐑 𝐱 Activity/Stress Factor fatty acids • Saturated fatty acids w/ chain lengths of 14
(myristic acid), and 16 (palmitic acid): most
CONDITION FACTOR potent in increasing plasma cholesterol levels
ACTIVITY FACTORS Mono- • Principally oleic acid
Confined to bed 1.2 unsaturated • Generally seen in Mediterranean diet (rich
Ambulatory 1.3 fatty acids in olive oils)
STRESS FACTORS (MUFA) • Decreases LDL, Increases HDL
≤20% TBSA 1.5
ω-6 Poly-
Burns 20%-50% TBSA 1.8 • Principally linoleic acid
unsaturated
>40% TBSA 1.8-2.0 • Decreases LDL, Decreases HDL: offsetting
fatty acids
Mild 1.2 the benefits of lowering LDL
(PUFA)
Moderate 1.4
Infection • Principally α-linolenic acid
Severe 1.8 ω-3 Poly-
Starvation 0.85 • Suppresses cardiac arrhythmias, reduces
unsaturated
Minor 1.1 plasma TAG, decreases risk for
Surgery fatty acids
Major 1.2 thrombosis, lowers blood pressure
(PUFA)
Skeletal 1.2 • Has little effect on LDL, HDL
Trauma Blunt 1.35 • Chemically classified as unsaturated fatty acids,
Closed head injury 1.4 but behave more like saturated fatty acids
Trans fatty

• Increases LDL, Decreases HDL
Again! Don’t waste memorizing the table above. I’ve included it so that you acids
would understand the process of calculating the TEE
• Formed during hydrogenation of vegetable oils

Dr. Rubio (in most deep-dried foods, baked goods)

DIETARY FIBER
ACCEPTABLE MACRONUTRIENT DISTRIBUTION RANGES (AMDR)
• Defined as nondigestible, non-starch carbohydrates and lignin
• Defined as a range of intakes for a particular macronutrient that present intact in plants
is associated with reduced risk of chronic disease while providing • The AI for dietary fiber is:
adequate amounts of essential nutrients o 25 g/day for women
o 38 g/day for men
• Softens stool; reduces risk for constipation,
hemorrhoids, and diverticula
• Increases bowel motility
Health • Decreases plasma cholesterol by increasing
effects of bile acid excretion in stool
dietary • Delays gastric emptying
fiber • Generates sensation of fullness
• Reduces postprandial blood glucose
AMDR. Based on Harrison's Principles of Internal Medicine, 20th edition

concentration
Saturated fat and trans fat <10% of total kcal
• Blunting of the glycemic response
Polyunsaturated fatty acids (PUDA) 5-10% of total kcal
Monounsaturated fatty acids (MUFA) 10-20% of total kcal GLYCEMIC INDEX (GI)
Simple sugars <10% of total kcal • Some carbohydrate-containing foods produce a rapid rise
followed by a steep fall in blood glucose concentration, whereas

DIETARY FATS
others result in a gradual rise followed by a slow decline – they
• Current data show that the type of fat is a more important risk differ in glycemic response (GR)
factor than the total amount of fat.
• Glycemic index (GI) ranks carbohydrate-rich foods on a scale of 0-
• Triacylglycerol (TAG) are quantitatively the most important 100 based on the GR they cause relative to the GR caused by the
class of dietary fats same amount (50 g) of carbohydrate eaten in the form of white
bread (or glucose)

• <55 NITROGEN BALANCE
• Evidence suggests that a low-GI diet improves • Occurs when the amount of nitrogen consumed = amount of
the glycemic control in diabetic individuals nitrogen excreted in the urine (primarily as urinary urea
Low GI
• Foods with low GI tends to create a sense of nitrogen), sweat, and feces

satiety over a longer period → may be helpful
in limiting caloric intake 1 g nitrogen = 𝟔. 𝟐𝟓 𝐠 𝐩𝐫𝐨𝐭𝐞𝐢𝐧
High GI • ≥70

ADDED SUGARS (SIMPLE SUGARS) • Nitrogen intake > nitrogen excretion

Positive
• Refer to sugars that are either added during food processing or • Seen in situations where tissue growth occurs –
nitrogen
packaging children, pregnancy, recovery from
balance
• Includes sugars (free, mono-, and disaccharides), sugars from emaciating illness
syrups and honeys, and sugars from concentrated fruit or • Nitrogen intake < nitrogen excretion
Negative
vegetable juices • Seen in inadequate dietary protein
nitrogen
• Recommended that these sugars represent no more than 10% of balance • Seen during physiological stresses (trauma,
total energy intake because of concerns that they may displace burns, illness, surgery)
nutrient-rich foods from the diet
• Associated with increased body weight and type 2 DM 6.4 BREASTFEEDING
• Association between sucrose consumption and dental caries HORMONES INVOLVED IN BREAST PHYSIOLOGY

Estrogen Initiates ductal development
DIETARY PROTEIN QUALITY MEASUREMENT
Responsible for differentiation of epithelium
• Protein Digestibility-Corrected Amino Acid Score (PDCAAS) Progesterone
and for lobular development
• Biological Value (BV) Prolactin Primary hormonal stimulus for lactogenesis
• Net Protein Utilization (NPU) Initiates contraction of myoepithelial cells →
• Protein Efficiency Ratio (PER) Oxytocin compression of alveoli → expulsion of milk
into the lactiferous sinuses
PROTEIN DIGESTIBILITY-CORRECTED AMINO ACID SCORE
(PDCAAS) TYPES OF MILK PRODUCED
• This refers to the FDA standard used to evaluate protein quality –
based on the profile of essential amino acids (EAA) - after • Secretion of colostrum by the alveolar cells of
correcting for the protein digestibility) the breast begin in the 12th – 16th week of
pregnancy
• This provides a method to balance intakes of poorer-quality
proteins w/ high-quality dietary proteins • Deep lemon-yellow liquid
• Value from 0 to 1 with 1 being the protein w/ the highest • Rich in immunoglobulins (IgA), contains more
quality minerals and amino acids
Colostrum
• Less sugar and fat
PROTEIN FROM ANIMAL PROTEIN FROM PLANT • Secretion persists for 5 days to 2 weeks (with
SOURCES SOURCES gradual conversion to mature milk by 4-6
Generally, has HIGHER Generally, has LOWER weeks)
QUALITY QUALITY • Vitamin K (virtually absent)
Egg, milks – Value of 1 Soybean – Value of 1 • Vitamin D (low content)

Proteins from animal sources (meat, poultry, milk & fish) have a high • Less minerals and amino acids
quality because they contain all the EAA in proportions similar to those Mature • More sugar and fat
required for synthesis of human tissue proteins. milk • Vitamin K (virtually absent)
Dr. Rubio
• Vitamin D (low content)

BIOLOGICAL VALUE (BV)
• Measures protein quality by calculating the nitrogen used for Vitamin K is virtually absent hence we must administer IM vitamin K to the
tissue formation divided by the nitrogen absorbed from food newborn to prevent bleeding diathesis. Vitamin D supplementation is also
• Value from 0 to 1 with 1 being the protein source w/ high recommended by the American Academy of Pediatrics.
Dr. Rubio
supply of essential amino acids

• In general, animal sources have a higher biological value than IMPORTANT COMPONENTS OF BREAST MILK
those of plant sources
• Serves as milk serum

Whey
𝐍𝐢𝐭𝐫𝐨𝐠𝐞𝐧 𝐮𝐬𝐞𝐝 𝐢𝐧 𝐭𝐢𝐬𝐬𝐮𝐞 𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧 • Shown to contain large amounts of IL-6
BV = Epidermal • Promotes growth and maturation of
𝐍𝐢𝐭𝐫𝐨𝐠𝐞𝐧 𝐀𝐁𝐒𝐎𝐑𝐁𝐄𝐃 𝐟𝐫𝐨𝐦 𝐟𝐨𝐨𝐝
growth factor newborn intestinal mucosa
• Important for protection against enteric
NET PROTEIN UTILITZATION (NPU) IgA
pathogens
• Measures protein quality by calculating the nitrogen used for • Very important for bowel maturation, as
tissue formation divided by the nitrogen ingested Lactose it supports the growth of Bifidus bacteria
• Value from 0 to 1 with 1 being the protein source w/ high which contribute to the neonate’s GI flora
supply of essential amino acids

𝐍𝐢𝐭𝐫𝐨𝐠𝐞𝐧 𝐮𝐬𝐞𝐝 𝐢𝐧 𝐭𝐢𝐬𝐬𝐮𝐞 𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧 TYPES OF BREASTFEEDING PRACTICES

NPU = • On-demand feeds are recommended
𝐍𝐢𝐭𝐫𝐨𝐠𝐞𝐧 𝐈𝐍𝐆𝐄𝐒𝐓𝐄𝐃

o Infants may bring hands to mouth, suck fists, get irritable, and
BOTTOMLINE: the denominator in BV is the nitrogen ABSORBED from cry when hungry
food; while the denominator in NPU is the nitrogen INGESTED • Plays an important role in mother-child bonding
Dr. Rubio

• Requires breast milk feeding

PROTEIN EFFICIENCY RATIO

• Determines the efficiency of a protein through the measurement (including from expressed milk, or from
of animal growth (rats) wet nurse)
• The computed value is compared to a standard value of 2.7 Exclusive • Does not allow infant to received
breastfeeding anything else BUT may allow ORS, drops
(standard value of casein protein):
or syrups (vitamins, mineral, medicine)
≥2.7 Excellent protein source especially in diseased state
<2.7 Poor protein source • Recommended up to 6 months of age

• Started when breast milk is no longer VITAMINS
sufficient to meet the nutrient • Refer to chemically unrelated ORGANIC COMPOUNDS occurring
requirements of infants, therefore other in small quantities in different natural foods
Complementary foods and liquids are needed, along with • Are necessary for growth and maintenance of good health
feeding breast milk • Are mainly classified into: WATER-SOLUBLE VITAMINS, FAT-
• Recommended from 6-24 months of SOLUBLE VITAMINS (see above)
age (but may continue breastfeeding • Are generally not synthesized by humans, but some vitamins can
beyond 2 years of age) be synthesized endogenously:

Wet nurse refers to a woman who breastfeeds and cares for another’s child VITAMIN SOURCE

Dr. Rubio
• From precursor steroids
• 7-dehydrocholesterol: found in
Vitamin D
NUTRITION epidermis; converted to vitamin D3 by
HIGHLIGHTS sunlight
https://qrs.ly/she03dg Vitamin K
Biotin • From intestinal microflora

Pantothenic acid
7. VITAMINS & MINERALS • From tryptophan (an essential AA),
Niacin
1. Definition of Terms requires vitamin B2, B6

2. Vitamins FAT-SOLUBLE VITAMINS VS. WATER-SOLUBLE VITAMINS

3. Minerals
• Vitamins are classified depending on their solubility, which is very
4. Interplay Between Vitamins & Minerals
important in distinguishing its means for absorption, toxicity, etc.
For the remaining section of the handout, we are going to focus ONLY on • Toxicity: occurs in accumulation of a certain nutrient in the body
the micronutrients. We have already discussed the macronutrients in the • Deficiency: occurs when a nutrient is lacking in the body
past sections. As the say: “It’s the little things that matter the most” "
%
$
#

Dr. Rubio FAT-SOLUBLE WATER-SOLUBLE
VITAMINS VITAMINS
7.1 DEFINITION OF TERMS Soluble in LIPID Soluble in AQUEOUS
Solubility
MEDIUM MEDIUM
Protein
In general, circulate
Carbohydrates LIVER and ADIPOSE
Macronutrients Storage freely in water-filled
Lipids TISSUE
Ethanol parts of the body
Nutrients Needs bile for
emulsification Directly absorbed in
Micronutrients
Vitamins Absorption Via CHYLOMICRONS → the small intestine →
Minerals lacteals → circulation circulation
→ liver
NUTRIENTS In general, circulate
LIVER and ADIPOSE
• Refer to constituents of food necessary to sustain the normal Storage freely in water-filled
TISSUE
functions of the body parts of the body
• Classified as either MACRONUTRIENT or MICRONUTRIENT Readily excreted via
Excretion Not readily excreted
(depending on the amount of nutrient consumed) urination
Risk for

MACRO-NUTRIENT MICRO-NUTRIENT HIGH LOW

Toxicity
Nutrients the body needs in Nutrients the body needs in
LARGER AMOUNTS SMALLER AMOUNTS Fat-soluble vitamins (ADEK) are prone to toxicity problems because they
Provides the body with energy Do not provide the body with are “too clingy” to your adipose tissues. They are not readily excreted
because of this property. REMEMBER: “Kapag ADEK ang isang tao sa’yo,
in the form of calories calories usually mas CLINGY siya, mas TOXIC.” N Q
P
O
PROTEINS, CARBOHYDRATES, VITAMINS
Another important point of discussion here is the need of BILE for the
LIPIDS, ETHANOL MINERALS
absorption of your ADEK vitamins. Prolonged biliary obstruction (i.e., LESS
Yes, ethanol is classified as a MACRONUTRIENT 8
; Among the 4 major
:
9 BILE IN SMALL INTESTINES) can cause clinically relevant VITAMIN
macronutrients, it provides the second largest amount of calories – 7 kcal/g DEFICIENCIES OF ADEK.
of alcohol. PHYSIOLOGICALLY, it is a NON-ESSENTIAL MACRONUTRIENT.

Dr. Rubio
But SOCIALLY, it is an ESSENTIAL MACRONUTRIENT & -

,
+
*
)
(
' SITES OF STORAGE OF VITAMINS IN THE BODY

Guys, remember, in biochemistry and nutrition, essential & non-essential STORAGE

nutrients are classified based on normal human diet needs: Essential MAJOR SITE OF STORAGE PERIOD IN
nutrients = “present in the diet”; Non-essential nutrients = “not
essential in diet”
THE BODY

Dr. Rubio FAT-SOLUBLE VITAMINS
VITAMINS VS. MINERALS Stellate cells of Ito 6 months
VITAMINS MINERALS Vitamin A (perisinusoidal space of the (Robbins &
Classification Both are MICRONUTRIENTS LIVER) as Retinyl Ester Cotran)
INORGANIC Vitamin D Liver ---
Composition ORGANIC substances Vitamin E Liver ---
substances
Easily destroyed by Not vulnerable to Vitamin K Liver ---
Vulnerability cooking with heat or heat, sunlight, or WATER-SOLUBLE VITAMINS
chemical reagents chemical agents Vitamin B9 3-4 months
Liver

Folic acid (Harrison’s)
7.2 VITAMINS Vitamin B12 3-4 years
Liver
Cobalamin (Harrison’s)
Vitamin B
Water-Soluble
complex; In general, the major site of storage of fat-soluble vitamins is LIVER >
Vitamins ADIPOSE TISSUE. Water-soluble vitamins are stored in the water-
Vitamin C
component of all organs, EXCEPT for Folic acid and B12 which are stored
Vitamins mainly in the liver. Thus, if you are a vegan not taking any vitamin
Vitamin A supplementation, it will take 3-4 years before B12 deficiency occurs 8 ;
:
9

Fat-Soluble Vitamin D Remember: Skin is the MAJOR SITE OF ENDOGENOUS SYNTHESIS of

Vitamins Vitamine E Vitamin D3 from 7-dehydrocholesterol. But its MAJOR SITE OF STORAGE
Vitamin K is the LIVER.

Dr. Rubio

✔INTEGRATION: PATHOLOGY VITAMIN A METABOLISM
Besides vitamin A storage, stellate cells of Ito are also responsible for
liver fibrosis when the liver has maximized its ability to perform
regeneration. On the other hand, the oval cells are responsible for liver
regeneration.

MAJOR SOURCES OF VITAMINS
MAJOR SOURCE
FAT-SOLUBLE VITAMINS
• Animal source: fish liver oils (halibut liver
oil), animal liver, eggs, dairy, meat
Vitamin A
• Plant source (β-carotene): carrot, yellow
fruits, green leafy vegetables (GLV)
• Cholecalciferol (D3): endogenous synthesis
Vitamin D from 7-dehydrocholesterol
• Ergocalciferol (D2): fungus
Vitamin E • Vegetable oils
• Phylloquinone (K1): GLV
• Menaquinone (K2): from bacterial flora synthesis
Vitamin K
• Menadione (K3): synthetic, water soluble
form in dietary supplements
WATER-SOLUBLE VITAMINS
Vitamin B1 • Starchy foods: Flour, rice, yeast; some animal
Thiamine products
Vitamin B2 • Milk and eggs
Riboflavin • Some plant products
Vitamin B3 • Livers, animal products, unrefined and
Niacin enriched grains
Vitamin B5
• Eggs, liver, yeast, some plant products
Pantothenic
• Can be synthesized by bacterial flora
acid Vitamin A Metabolism
Vitamin B6 • Animal products From Self-Assessment and Review of Biochemistry, 2nd Edition
Pyridoxine • Starchy vegetables

Vitamin B7 • Fate of β-carotene: → Retinal → Retinol
• Animal products, nuts Absorption • Fate of Retinyl ester: → Retinol
Biotin
Vitamin B9 • Retinol: form absorbed by intestinal cells
• Green leafy vegetables, legumes
Folic acid Transport • Retinol is esterified to Retinyl esters:
• Animal products ONLY from intestine transported in chylomicrons via lacteals
Vitamin • Only synthesized by microbes which are found to liver & lymphatics (from intestine → liver)
B12 in the intestine of animals • Uptake of Retinyl esters is mediated by
Storage
Cobalamin • Only water-soluble vitamin which cannot be Apolipoprotein E receptor of liver
derived from plant products Transport • Carried to target sites in the plasma as
Vitamin C from liver to trimolecular complex bound to: Retinol-
Ascorbic • Citrus fruits, some animal products target organs binding protein (RBP) & Transthyretin
acid
FUNCTIONS OF VITAMIN A

The table above is very useful in biochemistry and pediatrics (since

nutrition questions are also present in that exam!) J M Take into account
L
K • Rhodopsin: most light sensitive pigment
Maintenance
the bolded pieces of information. They are regarded as the RICHEST present in rods; formed by covalent
of vision
SOURCE of the specific vitamin. Please focus on them! association between 11-cis-retinal & opsin
Dr. Rubio

• Retinol: supports reproduction of cells

Normal • Retinoic acid: supports embryogenesis
FAT-SOLUBLE VITAMINS reproduction • Uses Retinoic acid receptors (RARs) and
VITAMIN A Retinoic X receptors (RXRs)
• In the strictest sense, vitamin refers to retinol • Deficiency of vitamin A can lead to
• Retinoids: refers to all compounds chemically related to retinol: Maintenance squamous metaplasia (columnar →
Retinal 11-cis-retinal: for normal vision of skin and squamous) of respiratory and intestinal
For normal morphogenesis, growth & cell mucosa tract → ↑ risk for infections (especially
Retinoic acid
differentiation measles infection)
For reproduction of cells Antioxidant • β-carotene: has antioxidant properties via
Retinol
Form absorbed by intestinal cells properties replenishment of vitamin E in the blood
Retinyl ester Storage form of vitamin A in liver

• Carotenoids: refers to provitamins of Vitamin A present in VITAMIN A DEFICIENCY

plants; as provitamins they can be metabolized to vitamin A • Most common vitamin deficiency worldwide (and in the
Most prevalent carotenoid in the food supply Philippines)
β-carotene • Most common cause of preventable blindness worldwide
that has provitamin A activity
Lutein Protection against macular degeneration Collective term for ALL ocular
Xerophthalmia
Lycopene Protection against prostate cancer manifestations of Vitamin A deficiency

Loss of sensitivity
Earliest SIGN of vitamin A deficiency
to green light
Nyctalopia Earliest SYMPTOM of Vitamin A
(night blindness) deficiency

Xerosis Dryness of the conjunctiva

White patches of keratinized epithelium
Bitot spots
appearing on the sclera

Keratomalacia Softening of the cornea

Corneal ulceration (painful) → corneal
Corneal ulceration
scarring (blindness)

Recall: SYMPTOM is a subjective experience of the patient. SIGN is an • Via α1-hydroxylase: found in the
objective phenomenon identified by another person (by you as the KIDNEYS
Conversion of 25-
future MD) "%
$
# • Serves as the RATE-LIMITING
Dr. Rubio OH-cholecalciferol →

STEP OF VITAMIN D
1,25-(OH)2-
METABOLISM
OTHER FEATURES OF VITAMIN A DEFICIENCY cholecalciferol
(calcitriol) • Most biologically active form of
Phrynoderma Epithelial metaplasia and keratinization →
vitamin D: 1,25-(OH)2-
or Toad Skin follicular hyperkeratosis
cholecalciferol (calcitriol)
Squamous metaplasia → loss of cilia,
RT, GIT • This step occurs when the level of
microvilli, and mucus production → ↑ stasis of Conversion of 25-
metaplasia Ca2+ is high
bacteria → ↑ risk of infection OH-cholecalciferol →
• Kidneys produce the inactive
24,25-(OH)2-
metabolite: 24,25-(OH)2-
VITAMIN A TOXICITY cholecalciferol
cholecalciferol (calcitroic acid) →
Common in arctic explorers eating polar bear (calcitroic acid)
Occurrence excreted in the urine
liver
Pseudotumor cerebri: headache, vomiting, FUNCTIONS OF VITAMIN D

Acute toxicity blurred vision, stupor (that may be confused • Regulation of calcium and phosphorus homeostasis
w/ brain tumor) • Immunomodulation and antiproliferative effects:
Chronic Increased risk for fractures (hip) o Prevents infection by Mycobacterium tuberculosis
toxicity Teratogenic in pregnancy o Less than 20 ng/mL of vitamin D: associated with increase in
incidence of colon, breast, and prostate cancer
VITAMIN A AS THERAPEUTIC AGENT • Mineralization of bones
β-carotene For cutaneous porphyria
All-trans-retinoic acid For acute promyelocytic leukemia VITAMIN D DEFICIENCY AND TOXICITY
13-cis-retinoic acid For acne • Normal reference range for circulating 25-OH-cholecalciferol:
(isotretinoin) For childhood neuroblastoma 20-100 ng/mL

VITAMIN D DEFICIENCY VITAMIN D TOXICITY

VITAMIN D • Rickets: before closure • ↑ Vitamin D → ↑ Ca2+
• Refer to group of sterols having a hormone-like function of epiphysis (children) • Blood vessel contraction →
Ergocalciferol Form of vitamin D obtained from fungal • Osteomalacia: after hypertension
(Vitamin D2) organisms (mushroom, ergots) closure of epiphysis • Calcification of soft tissues
Cholecalciferol From endogenous synthesis of 7- (adults) (metastatic calcification)
(Vitamin D3) dehydrocholesterol via UVB radiation
✔INTEGRATION: PHYSIOLOGY & PATHOLOGY

VITAMIN D METABOLISM
Calcium ions is the electrolyte capable of smooth muscle contraction!
Metastatic calcification: widespread calcification occurring in
HYPERCALCEMIC STATES. On the other hand, dystrophic calcification
occurs in damaged tissues in NORMOCALCEMIC STATES.

VITAMIN E
• Vitamin E is a collective name for all stereoisomers of tocopherols
& tocotrienols
• Most powerful naturally occurring antioxidant: serves as a
chain-breaking antioxidant
o Efficient radical scavenger → protects LDL & PUFAs in
membranes from oxidation
α-tocopherol Most potent form of vitamin E

VITAMIN E DEFICIENCY AND TOXICITY
VITAMIN E DEFICIENCY VITAMIN E TOXICITY
• Axonal degeneration →
muscle weakness
• Demyelination of • Reduces platelet aggregation
posterior columns & • Interferes with the effects of
spinocerebellar tract Vitamin K
• Acanthocytosis of RBCs
→ hemolytic anemia

Loss of position & vibration sensation occurs in demyelination of

posterior columns, while ataxia occurs in spinocerebellar tract
demyelination. RBCs are transformed to acanthocytes (prone to
hemolysis) due to loss of membrane protection from radicals in
vitamin E deficiency.
Vitamin D Metabolism and its Effects
From Self-Assessment and Review of Biochemistry, 2nd Edition TAKE NOTE: Neurologic presentation may appear similar to vitamin B12
Transport of dietary deficiency but without megaloblastic anemia, hypersegmented
• Via chylomicrons (similar to other neutrophils, or ↑ serum methylmalonic acid levels.
vitamin D from
fat-soluble vitamins obtained from Dr. Rubio
intestine to

the diet) THERAPEUTIC EFFECTS OF VITAMIN E

circulation • Oxygen-induced retrolental fibroplasia
Transport of dietary • Bronchopulmonary dysplasia
• Via vitamin D-binding proteins
& endogenous • Intraventricular hemorrhage of prematurity
(DBP)
vitamin D to the liver • Treatment of intermittent claudication
• Via 25-hydroxylase: found in the • Slowing of the aging process
LIVER
Conversion of • Most abundant circulatory form of The pathologies above are all related to radical formation & toxicity.
Thus, supplementing vitamin E could promote a better prognosis for these
vitamin D → 25- vitamin D: 25-OH-cholecalciferol
conditions. Besides vitamin E, the other well-known antioxidants are:
hydroxy- • Standard method for determining Vitamins A, C, E, zinc and selenium ❤
cholecalciferol vitamin D status of patient:
Dr. Rubio
measurement of 25-OH-
cholecalciferol

VITAMIN K WATER-SOLUBLE VITAMINS
• It is a naphthoquinone derivative with long isoprenoid side chain For the water-soluble vitamins section of my handout, I will focus on the
• Letter K is the abbreviation of the German word: Koagulation general functions of, and diseases associated with water-soluble vitamins.
vitamin The roles of these vitamins in intermediary metabolism will be discussed
further by Dr. Baticulon in his lecture R
S
Dr. Rubio
FORMS OF VITAMIN K
VITAMIN C (ASCORBIC ACID)

• Vitamin K has three major forms:
• Also known as anti-scorbutic (scurvy) factor
Vitamin K1
From dietary sources • Most animals synthesize vitamin C from glucose via the uronic
(Phylloquinone)
acid pathway
Vitamin K2
Synthesized by bacterial flora • Humans and other primates cannot endogenously synthesize
(Menaquinone)
vitamin C due to the absence of gulonolactone oxidase
Vitamin K3
Synthetic form (water-soluble) • Good reducing agent

(Menadione)
• Antioxidant
FUNCTIONS OF VITAMIN K • Posttranslational modification,
• Vitamin K is required for the post-translational gamma hydroxylation of lysine & proline in collagen
carboxylation of glutamic acid: necessary for Ca2+ binding to γ- synthesis
carboxylated proteins: • Converts dopamine to norepinephrine (via
General
• Factors II, VII, IX, X (1972) dopamine β-hydroxylase)
Coagulation factors Functions
• Protein C, Protein S • Iron absorption via conversion of ferric (Fe3+)
Protein in bone • Osteocalcin ions to ferrous (Fe2+) ions
• Nephrocalcin (inhibitor of calcium • Homogentisic acid synthesis
Protein in kidney • Bile acid synthesis (via 7α-hydroxylase)
oxalate stone formation)
• Conversion of folate to its active form
VITAMIN K DEFICIENCY AND TOXICITY • Adrenal steroid synthesis
• Newborns (especially premature) are susceptible to vitamin K
deficiency due to low fat stores, sterility of the infantile VITAMIN C DEFICIENCY VITAMIN C TOXICITY
intestinal tract, poor placental transport, & absent levels of • Scurvy:
• Nausea, vomiting,
vitamin K in breast milk o Corkscrew hair
diarrhea
o Swollen gums

VITAMIN K DEFICIENCY VITAMIN K TOXICITY • Calcium oxalate

o Bleeding diathesis
Bleeding diathesis (↑ Hemolysis → hyperbilirubinemia nephrolithiasis
o Poor wound healing
tendency to bleed) → kernicterus (CNS damage) • ↑ risk for iron toxicity
o Perifollicular & subperiosteal
(due to increased
Remember: Vitamin K is a fat-soluble vitamin. Thus, patients with low fat hemorrhages
stores (such as infants) are more susceptible to Vitamin K deficiency. Also dietary iron absorption)
• Weakened immune response
recall that vitamin K can be endogenously synthesized by the intestinal
microbiota, so absence leads to further deficiency. Finally, vitamin K is The functions of vitamin C in bold text are the “must-know” functions for
virtually absent in breastmilk. The abovementioned factors are the the PLE. In understanding the different vitamin deficiencies and toxicities,
rationale why we administer vitamin K in newborns 8 ;
:
9 always recall the general functions of the specific vitamin. For vitamin C

Dr. Rubio deficiency, you have “weak collagen” therefore you have fragile
capillaries (bleeding diathesis), poor wound healing, and corkscrew
hair. If you have vitamin C toxicity, more iron is absorbed in the proximal
duodenum → ↑ risk for iron toxicity

Dr. Rubio

VITAMIN B COMPLEX (VITAMINS B1, B2, B3, B5, B6, B7)
GENERAL
BIOCHEMICAL
ACTIVE FORM DEFICIENCY TOXICITY
FUNCTION /
REMARKS
• Wet beriberi
o Marked peripheral vasodilation (↓ TPR) → ↑ CO →
dilated cardiomyopathy (high-output cardiac
Decarboxylation failure) → pulmonary & peripheral edema (dyspnea)
reactions of alpha- • Dry beriberi
keto acids and o Polyneuropathy → symmetric muscle wasting
branched chain amino • Wernicke encephalopathy
acids o Acute, life-threatening, REVERSIBLE disorder
Thiamine No notable
Vitamin B1 o TRIAD: confusion, ophthalmoplegia, ataxia
pyrophosphate toxicity of
Thiamine REMARKS: • Korsakoff syndrome
(diphosphate) thiamine
• Erythrocyte o IRREVERSIBLE disorder
transketolase o Confabulation, personality changes, memory loss
activity is reduced • Wernicke-Korsakoff syndrome
in vitamin B1 o Combination of Wernicke and Korsakoff
deficiency syndrome
o Damage to mamillary bodies
o Seen in malnourished patients, chronic
alcoholism
Flavin adenine
• 2Cs of Vitamin B2 deficiency: cheilosis, corneal
dinucleotide (FAD) Coenzyme in redox No notable
Vitamin B2 vascularization
& Flavin reactions (electron toxicity of
Riboflavin • Magenta tongue (glossitis)
mononucleotide transfer) riboflavin
(FMN) • Seborrheic dermatitis

GENERAL
BIOCHEMICAL
ACTIVE FORM DEFICIENCY TOXICITY
FUNCTION /
REMARKS
• 3Ds of Vitamin B3 deficiency:
o Diarrhea
Coenzyme in redox o Dementia (and hallucinations)
reactions (electron o Dermatitis (C3/C4 dermatome circumferential
transfer) “broad collar rash – Casal necklace,
• Hepatotoxicity
Nicotinamide hyperpigmentation of sun-exposed limbs)
– most serious
adenine nucleotide REMARKS • Hartnup disease (autosomal recessive)
Vitamin B3 toxic reaction
(NAD) & • Synthesis from o Deficiency of neutral amino acid (e.g.,
Niacin / • Podagra –
Nicotinamide tryptophan tryptophan) transporters in PCT and enterocytes
nicotinic form of gout
adenine required B2 & B6 → neutral aminoaciduria & ↓ intestinal absorption
acid affecting the 1st
dinucleotide • 60 mg of → ↓ tryptophan for niacin synthesis
MTP joint
phosphate (NADP) tryptophan = 1 mg o Increases risk for vitamin B3 deficiency
• Facial flushing
of niacin • Other conditions capable of causing vitamin B3
• Increases HDL, deficiency
Decreases VLDL o Carcinoid syndrome (↑ tryptophan metabolism)
o Isoniazid use (↓ vitamin B6, which is needed for
niacin synthesis from tryptophan)
Vitamin B5 Essential component No notable
• Gopalan’s burning feet syndrome OR nutritional
Pantothenic Coenzyme A of Coenzyme A & fatty toxicity of
melalgia (pain in limbs)
acid acid synthase pantothenic acid
• Neurological manifestations, peripheral
Coenzyme for amino neuropathy, personality changes (due to deficiency
acid metabolism
of catecholamines & neurotransmitters)
pathways
• Convulsions (due to decreased GABA synthesis)
Needed in
Vitamin B6 Pyridoxal • Microcytic hypochromic anemia (due to Sensory
glycogenolysis (via
Pyridoxine phosphate decreased heme synthesis via ALA synthase) neuropathy
glycogen
• Sideroblastic anemia (due to iron excess in RBCs
phosphorylase) – 80%
of B6 is found in secondary to defective heme synthesis)
muscles • Pellagra-like syndrome (due to defective niacin
synthesis from tryptophan)
• Long-term antibiotic use or excessive ingestion
Involved in
Vitamin B7 of RAW WHITE EGG WHITES (large amounts of
Enzyme-bound carboxylation No notable
Vitamin H AVIDIN)
biotin reactions (adds 1- toxicity of biotin
Biotin o Avidin in egg whites AVIDLY BINDS biotin
carbon group)
o Causes dermatitis, enteritis, alopecia

Both Vitamins B6 and B12 can cause pellagra-like symptoms because both are needed to convert 60 mg of tryptophan to 1 mg of niacin. But between the two,
vitamin B6 is more important in this pathway, thus it is more likely to produce pellagra-like symptoms than vitamin B2 when deficient < C
B
A
@
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>
=

Dr. Rubio
VITAMIN B9, B12

VITAMIN B9 VITAMIN B12
Site of
Jejunum Ileum
absorption
Storage in
3-4 months 3-4 years
the liver
Methylcobalamin
Active Tetrahydrofolic
Deoxyadenosyl-
form(s) acid
cobalamin
Transfers one-
carbon units:
synthesis of Coenzyme for reactions:
Functions (1) methionine, (1) homocysteine →
(DNA (2) serine, methionine,
synthesis) (3) purine (2) methylmalonyl CoA
nucleotides, → succinyl CoA
(4) thymidine
monophosphate
• REVERSIBLE macrocytic, megaloblastic anemia
• Hypersegmented neutrophils
IRREVERSIBLE
subacute combined
Presentation
No neurologic degeneration of:
symptoms dorsal columns, lateral
corticospinal tracts,
spinocerebellar tracts
• ↑ homocysteine
• ↑ homocysteine
• Normal
Laboratory • ↑ methylmalonic
methylmalonic
parameters acid
acid
• ↓ folic acid
• ↓ folic acid

Vitamin B12 Absorption & Transport
From Robbins & Cotran Pathologic Basis of Disease, 10th Edition
✔INTEGRATION: PARASITOLOGY 7.3 MINERALS
Diphyllobothrium latum infection is associated w/ pernicious anemia
(megaloblastic anemia) because this tapeworm causes vitamin B12 • Minerals are classified depending on their daily requirement:
deficiency as it competes with its host for vitamin B12. macrominerals (major elements), microminerals (trace

elements), & ultra-trace elements
Folate supplementation can be given to B12 deficiency to mask the
• For this part of my handout, I will only discuss here the pertinent
hematologic symptoms, but NOT THE NEUROLOGIC SYMPTOMS!
Moreover, please take note that methylmalonic acid is increased in B12 minerals involved in biochemistry & nutrition. I will let
deficiency due to failure to convert it to succinic acid. physiology handle most of the major elements!
It is also noteworthy to mention that both vitamin deficiencies have FEATURES EXAMPLES
increased levels of homocysteine – a risk factor for CARDIOVASCULAR • Calcium
DISEASE. < C
B
A
@
?
>
= • Magnesium
Dr. Rubio

Macrominerals • Phosphorus
✔INTEGRATION: OB-GYNE Daily requirement:
(major • Sodium
Folic acid supplementation of 400 ug of folic acid daily must be given >100 mg/day
elements) • Potassium
to pregnant women with no history of offspring with neural tube defect
(NTD) for at least 1 month prior to conception and during 1st • Chloride
trimester to ↓ risk for NTDs. For mothers with history of offspring with • Sulfur
NTDs, the daily folic acid supplementation is shifted to 4000 ug. • Chromium
• Copper
ABSORPTION & TRANSPORT OF VITAMIN B12 Microminerals Daily requirement: • Fluorine
(trace elements) <100 mg/day • Iron
• Vitamin B12 is freed from binding proteins in food via the action
of pepsin in the stomach • Manganese
• Zinc
• Freed vitamin B12 binds to a salivary protein, haptocorrin
• Iodine
(transcobalamin I) Ultra-trace Daily requirements: <1
• Molybdenum
• In the duodenum, bound vitamin B12 is released from elements mg/day
• Selenium
haptocorrin by the action of pancreatic proteases → freed vitamin
B12 associated with intrinsic factor (a protein released by the Tips on memorizing tables with large content. In this case, I would only
parietal cells of the stomach) memorize the ultra-trace elements. Then, the more familiar ones are
surely in the micromineral group (except for iron & zinc). Doing that
• The vitamin B12-intrinsic factor complex is transported to the
technique, you can memorize this table in 5 seconds 8 ;
:
9
ileum, where it is endocytosed by ileal enterocytes that expressed
Dr. Rubio
cubilin receptors on their luminal surfaces IRON
• Within the ileal cells, vitamin B12 associates with transcobalamin II • Iron is found in numerous molecules of the body, but it is classified as
→ vitamin B12-transcobalamin II complex is secreted into the a micromineral because its daily requirement is <100 mg/day:
plasma → liver (for storage) and target organs for peripheral use Hemoglobin Transport of oxygen in the blood

SUMMARY OF VITAMIN DEFICIENCIES & TOXICITIES Myoglobin Storage of oxygen in the muscle
DEFICIENCIES TOXICITIES Cytochrome c Involved in the ETC
FAT-SOLUBLE VITAMINS Cytochrome P450 Hydroxylation of xenobiotics
Catalase Degradation of hydrogen peroxide
• Xerophthalmia
• Pseudotumor Tryptophan
Vitamin A • Squamous metaplasia Oxidation of tryptophan
cerebri pyrrolase
• Toad skin
• Hypertension IRON METABOLISM

• Rickets
Vitamin D • Metastatic
• Osteomalacia
calcification
• Reduction of
• Demyelination of
platelet
posterior columns &
Vitamin E aggregation
spinocerebellar tract
• Vitamin K
• Hemolytic anemia
interference
Vitamin K • Bleeding diatheses • Hemolysis
WATER-SOLUBLE VITAMINS
• Beriberi
Vitamin B1
• Wernicke-Korsakoff ---
Thiamine
Syndrome
Vitamin B2 • Cheilosis
---
Riboflavin • Corneal vascularization Iron Metabolism
• Podagra From Self-Assessment and Review of Biochemistry, 2nd Edition
Vitamin B3
• Pellagra • Hepatotoxicity IRON ABSORPTION
Niacin
• Facial flushing • Proximal duodenum
Vitamin B5 • Fate of heme iron: absorbed by heme transporter
• Gopalan’s burning feet
Pantothenic --- • Fate of ferrous (Fe2+) iron: absorbed by
syndrome
acid divalent metal transporter 1 (DMT 1)
Site of
• Sideroblastic anemia • Fate of ferric (Fe3+) iron: reduced to its
absorption
Vitamin B6 • Microcytic, hypochromic • Sensory ferrous form by a brush border enzyme,
(luminal
Pyridoxine anemia neuropathy duodenal cytochrome b
side)
• Pellagra • Vitamin C: favors reduction of ferric iron to
Vitamin B7 • Dermatitis, enteritis, ferrous iron
---
Biotin alopecia • DMT1: can also transport a wide variety of
Vitamin B9 • Macrocytic, megaloblastic divalent cations (Co2+, Zn2+, Pb2+, Cu2+)
--- • (1) can be stored as ferritin
Folic acid anemia
• Macrocytic, megaloblastic • (2) can be transferred across the basolateral
Vitamin membrane → blood circulation via ferroportin
anemia
B12 --- Fate of iron • Hephaestin: a Cu-containing protein
• Subacute combined spinal
Cobalamin in the associated w/ ferroportin (at the basolateral
degeneration
• GI symptoms enterocytes side of enterocytes) which converts ferrous
Vitamin C • Scurvy iron to its ferric state
• Iron toxicity
Ascorbic • Decreased immune • Ferric state: it is the favored form of iron when
• Calcium oxalate
acid response being transported by transferrin in the circulation
nephrolithiasis

FATE OF IRON IN MACROPHAGES DISORDERS OF COPPER METABOLISM
• Macrophages phagocytose senescent RBCs at MENKES DISEASE WILSON DISEASE
Fate of
the end of their lifespan Mode of
hemoglobin X-linked recessive Autosomal recessive
• Ingested hemoglobin → heme + globin inheritance
Fate of Cu-transporting
• Globin + other proteins → amino acid pool ATP7A ATP7B
globin ATPase affected
Fate of • Heme → Biliverdin (via heme oxygenase) + Whole body Cu ↓ ↑
heme iron → bilirubin (via biliverdin reductase) Free serum Cu ↓ ↑
• Iron is shuttled back to the circulation via Urinary Cu ↓ ↑
Fate of iron
ferroportin (in the ferric state) Cu is not Storage of Cu in
Pathophysiology mobilized from parenchyma of

REGULATION OF IRON METABOLISM

intestine different organs
• Hepcidin: is the chief regulator of systemic iron homeostasis
(synthesized by the liver) • Kayser-Fleischer
• Kinky or steely
• It is upregulated when there are high amounts of iron in the rings
hair
blood, and in cases of inflammation Salient features • Liver dysfunction
• Neurologic
• Hypoxia downregulates hepcidin → allows ↑ iron in blood circulation • Neuropsychiatric
degeneration
• It binds to ferroportin → internalization and degradation of abnormalities
ferroportin → decreased export of iron into circulation &
depressed iron recycling by macrophages

Hepcidin is a positive acute-phase reactant. It is increased in cases of

inflammation to pre-empt the possibility of infection. Bacterial organisms
reproduce faster in the presence of iron, hence hepcidin is upregulated to
decrease the pool of iron in circulation. That is also the rationale why we
do not administer iron in patients with ongoing bacterial infection.

Anemia of inflammation occurs in patients with prolonged inflammation.

This occurs due to upregulation of hepcidin which decreases iron pool in
circulation

Dr. Rubio

IRON STORAGE
Kayser-Fleischer Ring deposition at Descemet Layer of Cornea
• Human body can store up to 1g of iron, majority of which is From https://webeye.ophth.uiowa.edu/eyeforum/cases/97-kayser-fleischer-ring-
bound to apoferritin
wilsons-disease.htm
• Complex of ferric iron + apoferritin = ferritin ZINC
• WATER-SOLUBLE • An integral component of many metalloenzymes in the body
Ferritin • Seen largely in intestinal cells, liver, spleen, • Involved in the synthesis and stabilization of proteins, DNA,
bone marrow RNA, and plays a structural role in ribosomes & membranes
• Indicator of body iron stores
• A WATER-INSOLUBLE, partly degraded Alcohol

Ethanol → acetaldehyde
form of ferritin containing iron dehydrogenase
• Iron is not easily mobilized from Carbonic Important in buffer
Serves as
Hemosiderin hemosiderin unlike ferritin anhydrase system
cofactor in
• Can be detected in histological stains (Prussian Porphobilinogen Heme synthesis
the following
blue stain) in conditions of iron overload synthase Inhibited by lead
enzymes:
• Index of iron overload Cytoplasmic Superoxide → hydrogen
superoxide peroxide
Classic triad of hemochromatosis: cirrhosis, diabetes mellitus, skin dismutase (SOD) Also requires copper
pigmentation (bronzing)
• Form supersecondary protein structures
Dr. Rubio
Structural
(i.e., zinc fingers)

IRON TRANSPORTER function

• Stabilizes the structure of insulin hormone
• Transferrin – transports ferric form of iron in plasma
(synthesized by the liver) • Absolutely required for normal
spermatogenesis
Quick review: Ferrous (Fe2+) is the form of iron that can be absorbed by Reproduction
• Fetal growth
DMT-1 at the luminal surface of the enterocytes.
• Embryonic development
Ferric (Fe3+) is the form of iron that can form a complex with transferrin
and apoferritin. ACRODERMATITIS ENTEROPATHICA
Dr. Rubio
• Rare autosomal recessive disorder characterized by

abnormalities in zinc absorption → ↓ zinc in the body

IRON METABOLISM • Presents with: vesicular rashes w/ pustular crusting, scaling
https://qrs.ly/i8e03e4 & erythema of the extremities, face, perineum
• Also has diarrhea, alopecia

COPPER
✔INTEGRATION: PEDIATRICS
Transfers electrons Diphyllobothrium latum infection is associated w/ pernicious anemia
Cytochrome c
from cytochrome c to (megaloblastic anemia) because this tapeworm causes vitamin B12
oxidase
oxygen in ETC deficiency as it competes with its host for vitamin B12.
Dopamine β- Dopamine →
hydroxylase norepinephrine MANGANESE
Oxidizes iron (from Arginine → urea +
Serves as Ferroxidases Arginase-I
ferrous form → ferric ornithine
cofactor in the (Hephaestin) Serves as
form) Transfers sugars in
following cofactor Glycosyltransferases
Forms cross-links in proteoglycan synthesis
enzymes: in the
Lysyl oxidase collagen & elastin Pyruvate Pyruvate → oxaloacetate
fibers following
carboxylase in gluconeogenesis
Tyrosinase Synthesis of melanin enzymes:
Superoxide → hydrogen
Cytoplasmic Superoxide → Mitochondrial SOD
peroxide
superoxide hydrogen peroxide
Mitochondrial SOD requires Manganese; CytoplaZmic SOD requires

dismutase (SOD) Also requires zinc Copper and Zinc

Dr. Rubio

MOLYBDENUM Remember: Zinc stabilizes the structure of insulin; Chromium potentiates
• Serves as cofactor for oxidase enzymes the action of insulin
Dr. Rubio

Serves as Aldehyde oxidase Drug metabolism

cofactor
Sulfite oxidase
Sulfite → sulfate 7.4 INTERPLAY BETWEEN VITAMINS & MINERALS
in the (methionine, cysteine) Zinc • Interferes the mobilization of vitamin A
following Hypoxanthine → xanthine deficiency from liver stores
Xanthine oxidase
enzymes: Xanthine → uric acid Alcohol • Interferes w/ conversion of retinol →

MOOOlybdenum for Oxidase enzymes intoxication retinaldehyde in the eyes

Dr. Rubio

Vitamin E
OTHER MINERALS • Interferes w/ the effects of vitamin K
toxicity
FUNCTION DEFICIENCY TOXICITY • Favors iron absorption by converting ferric
Constituent Vitamin C
Macrocytic ions → ferrous ions
Cobalt of intake
anemia • Converts folate into its active form
cobalamin
• Decreased absorption of copper → ↓ iron
Potentiates Impaired Zinc toxicity
absorption (since hephaestin contains Cu)
Chromium the action of glucose
• Irreversibly binds Zn in intestine → ↓ Zn
insulin tolerance
absorption
Constituent Excess
• Irreversibly binds to Ca → ↓ Ca absorption
Fluoride of bone & Dental caries Fluorosis phytates
• Irreversibly binds to nonheme Fe → ↓
teeth
nonheme Fe absorption
Cofactor of Neurologic

Molybdenum oxidase dysfunction

enzymes Xanthinuria

Keshan Kaschin-

cardio- Beck

myopathy: disease:
Selenium Antioxidant
necrosis of garlic breath,
cardiac brittle nail,
muscle fibers myopathy

8. COMPLEX MOLECULES
STRUCTURE FUNCTIONS DISEASES
• Cell surface recognition • I-cell disease

• Cell surface antigenicity (inclusion cell
• Components of the disease):
• Proteins to which
extracellular matrix failure of GA to
oligosaccharides (short
• Cell trafficking: distribution of phosphorylate
chains of
synthesized molecules to the mannose
carbohydrates) are
GLYCOPROTEINS different cell compartments or residues → ↓
attached.
MUCOPROTEINS extracellular space mannose-6-
• The oligosaccharides are
• Mucins: lubricant and phosphate on
usually attached to amino
Proteins > protective agent in the glycoproteins
acids serine (O-linked,
Carbohydrates gastrointestinal and urogenital → proteins are
synthesized in gOlgi
tracts secreted to
bodies), or asparagine
• Transferrin, ceruloplasmin: extracellular
(N-linked, synthesized in
transport molecules space (rather
eNdoplasmic reticulum).
• HGC, TSH: hormones than to
• Immunoglobulins: lysosomes)
immunologic function
• Unbranched
polysaccharides
consisting of repeating
• Hyaluronic acid: cell
disaccharide units,
migration and wound repair
alternating acidic
• Chondroitin sulfate: principal
sugar-amino sugar.
components of cartilage, found
o Acid sugars:
in sites of calcification, most MUCOPOLY-
GLYCOSAMINO- glucuronic acid,
abundant GAG SACCHARIDOSES
GLYCANS (GAGs) From Lippincott Illustrated Reviews iduronic acid
• Keratan sulfate: maintenance o Hunter
MUCOPOLY- Biochemistry, 7th Edition o Amino sugars:
of corneal transparency syndrome
SACCHARIDES glucosamine,
• Heparin: anticoagulant o Hurler
galactosamine
• Heparan sulfate: receptors for syndrome
Carbohydrates > • Galactose and sulfate
cell growth and cell-cell o Morquio
Proteins also usually present
communication, maintains syndrome
• Except for hyaluronic
charge selectiveness of renal
acid, the GAGs are
glomerulus
normally linked to a
• Dermatan sulfate: main GAG
protein core, and the entire
of skin
structure is called a
proteoglycan:

Diagram of Ground Substance. (Purple structure
= core protein)
From Wheater’s Functional Histology, 6th Edition

The latter term (-proteins or -glycans) represent the more abundant biomolecule. PROTEINS in glycoproteins, and CARBOHYDRATES in GAGs.

Dr. Rubio
STRUCTURE FUNCTIONS DISEASES/REMARKS
• Phosphatidylcholine:
(lecithin) most abundant,
• Phospholipid in which storage of choline component • Phospholipids in
an alcohol (“X”) is of acetylcholine the outer leaflet of
attached by a cell membrane:
• Phosphatidylethanolamine:
phosphodiester bridge o Phosphatidylcholine
(cephalin)
to diacylglycerol. o Sphingomyelin
• Phosphatidylserine:

Flips from the inner leaflet to
GLYCERO- • It is “X” that varies • Phospholipids in
the outer leaflet → signals
PHOSPHOLIPIDS among the different the inner leaflet of
APOPTOSIS
PHOSPHO- glycerol-phospholipids. cell membrane:
• Phosphatidylinositol:
GLYCERIDES Simplest is o Phosphatidyl-
reservoir of arachidonic acid
phosphatidic acid, ethanolamine
in cell membranes, source of
where X = hydrogen o Phosphatidylserine
inositol triphosphate + DAG,
atom. (e.g., if X = o Phosphatidyl-
which are 2nd messengers
choline, then the ethanolamine
(signal transduction)
compound is
• Cardiolipin: antigenic, cross
phosphatidylcholine)
reacts with antibodies to
syphilis
• Sphingomyelin: only
significant
sphingophospholipid in
SPHINGO- • Phospholipid with a humans, constituent of

PHOSPHOLIPIDS sphingosine backbone myelin sheath, which
insulates the axons of nerve
fibers and increase nerve
conduction
• Derivatives of
ceramide in which a
long-chain fatty acid is
attached to a
sphingosine backbone.

(NICE TO KNOW): • Essential component and
GLYCOLIPIDS • Name of glycolipid contribute to the asymmetry • SPHINGO-
GLYCOSPHINGO- depending on “X”: of the cell membrane (outer LIPIDOSES
LIPIDS o Ceramide: leaflet) o Tay-Sachs disease
hydrogen atom • Play a role in cell adhesion o Niemann-Pick
Lipid > o Cerebroside: and recognition, growth, and disease
Carbohydrate glucose or galactose development o Gaucher disease
o Globoside: di-, tri-, or • Important in neural tissue
tetrasaccharide
o Ganglioside:
N-acetylneuraminic
acid
o Sulfatide: sulfated
glucose
• Derived from 20-carbon

fatty acid, arachidonic
acid which is cleaved
from cell membrane
phospholipids by the
EICOSANOIDS
enzyme phospholipase
PROSTAGLANDINS
A2
PROSTACYCLINS
• Products of
THROMBOXANES
cyclooxygenases:
LEUKOTRIENES
o Prostacyclin
LIPOXINS
o Thromboxane

o Prostaglandin
• Products of
lipoxygenases:
o Leukotrienes
o Lipoxins

Arachidonic Acid Metabolites and their Roles in Inflammation
From Robbins & Cotran Pathologic Basis of Disease, 10th Edition

PHOSPHOGLYCERIDES
https://qrs.ly/qee03e8

COMPOSITION OF GLYCOSAMINOGLYCANS
GAG SUGAR UNITS LOCATION
Skin, synovial
fluid, bone,
Hyaluronic • N-acetylglucosamine
cartilage, vitreous
acid Glucuronic acid
humor, embryonic
tissues
Chondroitin • N-acetylgalactosamine Cartilage, bone,
CELLULOSE VS. LIGNIN
sulfate • Glucuronic acid CNS CELLULOSE LIGNIN
Cornea, cartilage, Most abundant compound on Second most abundant
Keratan • N-acetylglucosamine earth compound on earth
loose connective
sulfate Galactose Polymer of non-
tissue
• Glucosamine Mast cells, liver, Polymer of carbohydrate carbohydrate aromatic
Heparin compounds (polyphenols)
• Iduronic acid lung, skin
Skin, kidney Important compound in the
Heparan • Glucosamine Forms the primary cell wall
basement formation of secondary cell
of plants
sulfate • Glucuronic acid wall of plants
membrane
(+) glycosidic bonds (+) ester or ether bonds
Dermatan • N-acetylgalactosamine Skin, wide
sulfate distribution Hydrophilic Hydrophobic
• Iduronic acid

CLINICAL CORRELATES: GLYCOPROTEINS
I-CELL DISEASE
• Pathology:
o Mannose residue of oligosaccharide is not phosphorylated;
hence, the glycoprotein does not reach the lysosome where it is
supposed to be degraded
o Large inclusion bodies in cells
• Clinical Presentation:
o Skeletal abnormalities, restricted joint movement, coarse facial
features, severe psychomotor impairment

INFLAMMATION Structure of Lignin
• Circulating leukocytes adhere to the endothelium through From https://i2.wp.com/www.differencebetween.com/wp-
content/uploads/2017/08/Difference-Between-Lignin-and-Cellulose-
selectins on the latter’s cell surface 2.png?w=621&ssl=1

POLYPHENOLS
INFLUENZA VIRUS
• Refers to a large family of naturally occurring organic
• Contains neuraminidase, glycoprotein that allows new viruses to
compounds characterized by multiples of phenol units
exit infected cells

HUMAN IMMUNODEFICIENCY VIRUS TYPE 1
• gp120: surface glycoprotein used to attach to cells
• gp41: surface glycoprotein used to fuse with the host cell membrane

CLINICAL CORRELATES:
SPHINGOLIPIDS AND GLYCOLIPIDS
MULTIPLE SCLEROSIS
Structure of a Phenol
• Demyelinating disease in which there is loss of both From https://ehs.ucsc.edu/programs/research-safety/images/phenol.png
phospholipids and sphingolipids from white matter, with
resulting ↓ CSF phospholipids Always remember: Usually, the definition of a term is in its name already.
• Clinical presentation: “poly” + “phenols” = multiple phenol units
Dr. Rubio
o Episodes of neurologic dysfunction, with attacks separated
• A phenol compound is a chemical structure formed by attaching

by periods of partial or complete remission
o May present with sensory symptoms, motor weakness, an aromatic benzenoid ring to a hydroxyl (-OH) group (as is
autonomic dysfunction, eye symptoms, depression, or other found in alcohols)
• Important examples of polyphenols and their respective functions:
neurologic deficits that reflect primary CNS involvement
• In plants: floral pigmentation, UV filtration
ABO SYSTEM OF BLOOD TRANSFUSION and nitrogen fixation
• Discovered by Landsteiner in 1900 • In humans: anti-oxidative, anti-
inflammatory, anti-carcinogenic properties
• The membranes of the red blood cells of most individuals contain
one blood group substance of type A, type B, type AB, or type O • May be helpful in cardiovascular disease
Flavonoids
prevention
• On membranes of red blood cells, the oligosaccharides that
determine the specific natures of the ABO substances appear to • Has hormone-like properties (such as
be mostly present in glycosphingolipids: estrogen)
• Most common group of polyphenolic
Type A N-acetylgalactosamine compounds in the human diet
Type B Galactose • Serves as precursors to phytoestrogens (has
Type AB Both hormone-like properties)
Type O Neither Lignans
• Have potential for anti-oxidative and anti-
carcinogenic effects
• Forms the secondary cell walls of plants Isozymes are structurally different, but they perform the same function. For
• Fills the spaces in the cell wall between example, glucokinase and hexokinase both catalyze the phosphorylation of
Lignin glucose to glucose-6-phosphate but have different structures. Hence, they
cellulose, especially in the vascular and
are considered isozymes.
support tissues of plants (xylem)

Dr. Rubio
• Found in coffee beans and is chemically

Phenolic
unrelated to caffeine 9.2 CLASSES OF ENZYMES
acid
Has anti-oxidative and anti-inflammatory effects
• Add oxygen or remove hydrogens
• Has anti-oxidative, anti-inflammatory
Oxidoreductases (oxidases, dehydrogenases)
Stilbenoids effects, anti-diabetic effects
(Class I) • Add hydrogens (reductases) to
• Further research is warranted
substrates
In general, polyphenols have anti-oxidative, anti-inflammatory, & anti- • Move chemical groups (glycosyl,
carcinogenic effects. But keep in mind that further research is needed Transferases
methyl, phosphoryl) from one
to establish the biologic effects of these compounds to the human (Class II)
substrate to another
body. Remember that the most common group of polyphenolic compounds
in the human diet is flavonoids. • Cleave substrate bonds using water
Dr. Rubio (adding H+ or OH-) to the cleavage
Hydrolases

products
(Class III)
9. GENERAL ENZYMOLOGY • Subtypes include peptidases,
1. Overview of Enzymes lipases, etc.
2. Classes of Enzymes Lyases • Catalyzes cleavage of C-C, C-S, and
3. Properties of Enzymes (Class IV) certain C-N bonds
4. Enzyme Kinetics Isomerases • Rearrange substrate molecules to
5. Regulation of Enzyme Activity (Class V) form a different isomer
6. Rate-Limiting Enzymes • Catalyze the formation of bonds
7. Clinical Correlates Ligases between C and O, S, and N coupled

(Class VI) to hydrolysis of high-energy
phosphates (e.g., ATP hydrolysis)

The abovementioned enzyme classes are the 6 major classes of enzymes

according to the International Union of Biochemists (IUB)

Dr. Rubio

OTHER NOTABLE ENZYMES
Phosphatases Remove phosphate groups
Phosphorylases and
Add phosphate groups to substrates
Kinases

CLASSES OF ENZYMES
https://qrs.ly/3ce03eb

9.1 OVERVIEW OF ENZYMES
• Generally, enzymes are protein catalysts that increase the 9.3 PROPERTIES OF ENZYMES
velocity of a chemical reaction and are not consumed during the
reaction they catalyze
o Enzymes lower the activation energy of a chemical reaction →
increases the velocity of the chemical reaction
o Enzymes do not change the energy of the reactants and
products; it has no effect on equilibrium (it only hastens both
forward and reverse reactions, thus reaching equilibrium
faster)

From Harper’s Illustrated Biochemistry, 30th edition
Exception to the proteinaceous nature of enzymes are ribozymes (RNA
with catalytic activity) The binding of a substrate to its enzyme is very specific. Even if the

Dr. Rubio molecular formula remains the same, if you switch the position of the blue
DEFINITION OF TERMS and the green ball in the molecule above, the substrate will no longer be
able to bind to the enzyme,
Substrate Refers to the substance on which an enzyme act

Dr. Rubio
Refers to the substance produced by the action of • Contain an active site for the substrate, held together by
Product
enzyme on the substrate hydrogen bonds
• Highly efficient
• Highly specific (Lock and Key vs Induced Fit Models)
• Some enzymes require nonproteins for enzymatic activity
(cofactors, coenzymes)
• Compartmentalized in different areas of the cell (cytoplasm,
mitochondria, SER, RER, Golgi apparatus)
• Can be regulated or inhibited

LOCK AND KEY MODEL VS INDUCED FIT MODEL

LOCK AND KEY MODEL INDUCED FIT MODEL
• Binding of substate to a
Lowering of Activation Energy specific part of the enzyme

→ INDUCES
Think of activation energy as the “GREAT WALL OF CHINA” that you must • The enzyme and substrate CONFORMATIONAL
overcome so that a chemical reaction would move forward. If that wall is
FIT TOGETHER (like a key CHANGES in the active site
“lowered by enzymes” the chemical reaction would be FASTER since less
effort is needed to climb that GREAT WALL J
M
L
K to a lock) of the enzyme

Dr. Rubio • Enzyme changes shape
• Isozymes are physically distinct versions of a given enzyme, each during or after binding the
of which catalyzes the same reaction substrate
LOCK AND KEY MODEL INDUCED FIT MODEL At point A, as you increase the amount the substrate, the velocity of the reaction
• Failed to explain the • Can explain the dynamic also increases (first order reaction). At point C, even if you increase the amount
of substrate present, the velocity of the reaction remains the same because the
dynamic changes that changes that accompany
enzymes are already saturated (zero-order reaction).
accompany catalysis catalysis
Dr. Rubio
• Less accepted model • More accepted model MAXIMAL VELOCITY (Vmax)

• Maximal number of substrate molecules converted to product
per unit time

MICHAELIS CONSTANT (Km)

• The substrate concentration at which Vi is half the maximal
velocity (Vmax ÷ 2) attainable at a particular concentration of
enzyme

Induced Fit Model
Lock and Key Model

HOLOENZYMES, APOENZYMES, COFACTORS, COENZYMES

• Simple enzymes: enzymes consisting only of proteins
• Complex enzymes: enzymes consisting of a protein part
(apoenzyme) + nonprotein component
• Some enzymes require nonproteins for enzymatic activity

• Refers to the active enzyme + nonprotein

Holoenzyme
component
FACTORS THAT AFFECT THE RATE OF A REACTION

• Refers to the enzyme without its nonprotein
• Substrate concentration
Apoenzyme component
• Rendered INACTIVE • Temperature
• pH
• Refers to the nonprotein component that is a
Cofactor

metal ion (e.g., minerals) Increasing the substrate concentration will increase the velocity of a
reaction until you reach saturation point. Increasing the temperature will
• Refers to the nonprotein component that is a
also increase the rate of a reaction, until the enzymes are denatured.
small organic molecule Enzymes have different optimal pH. Example: pepsin in stomach thrives in
Coenzyme • Usually derived from vitamins an acidic pH. Whereas Trypsin, Lipase from pancreas thrive in basic pH.
• Can be a COSUBSTRATE or PROSTHETIC

Dr. Rubio
GROUP LINEWEAVER-BURK PLOT

• Refers to coenzymes that only • Reciprocal of the Michaelis-Menten equation
Cosubstrate
TRANSIENTLY associate with the enzyme • Used to calculate Km and Vmax, as well as to determine the
Prosthetic • Refers to coenzymes that are permanently mechanism of action of enzyme inhibitors
group associated with the enzyme

EFFECTORS

• Are not required for the function of an enzyme

POSTIVE EFFECTOR NEGATIVE EFFECTOR

• Will ↑ the rate of a reaction • Will ↓ rate of a reaction

Cofactors and coenzymes are essential for function. Effectors are optional.
Most vitamins, especially the water-soluble ones, serve as coenzymes for
chemical reactions, which is why they are important. In the absence of
these vitamins, the enzymes will not work.

Dr. Rubio

9.4 ENZYME KINETICS

MICHAELIS-MENTEN EQUATION From Harper’s Illustrated Biochemistry, 30th edition

• Describes how reaction velocity varies with substrate Compared to the Michaelis-Menten plot, which is hyperbolic, the
concentration Lineweaver-Burk plot is a straight line.
Dr. Rubio
• Assumes that:

o [S] much greater than [E] ENZYME INHIBITOR

o [ES] is constant • Any substance that can diminish the velocity of an enzyme-
o [P] is low catalyzed reaction
• Enzymes that follow Michaelis-Menten kinetics have a hyperbolic • Inhibition can be:
curve o Reversible
o Irreversible

Compare the effect of aspirin and NSAIDs on the enzyme cyclooxygenase.

Vi Initial reaction velocity NSAIDs (e.g., mefenamic acid, ibuprofen) are reversible inhibitors. Aspirin
Vmax Maximal velocity is an irreversible inhibitor.

Km Michaelis constant

Dr. Rubio
[S] Substrate concentration TYPES OF ENZYME INHIBITORS

Effect of substrate concentration on the initial velocity of an
enzyme-catalyzed reaction

COMPETITIVE NONCOMPETITIVE 9.6 RATE-LIMITING ENZYMES
Inhibitor is shaped Inhibitor binds to
• Rate-limiting enzyme: the slowest step of a metabolic pathway
similar to substrate enzyme somewhere
Mechanism which determines the overall rate of a metabolic pathway
and competes for other than the active

binding site site and halts cata-lysis
Think of a group of friends who joined an obstacle course racing but in a
Reversal Increase [S] Increase [E] group category. The friends are the different “enzymes of a pathway.” The
Km Increased Not changed slowest among the friends is the “rate-limiting step.” And of course, since
Vmax Not changed Lowered you are real friends “walang iwanan dapat.” Even the fastest friend should

wait for the slowest friend. Thus, the rate-limiting step determines the
An example of competitive inhibition is the effect of statin on the enzyme
overall rate of a metabolic pathway
HMG CoA reductase. An example of noncompetitive inhibition is the effect
Dr. Rubio
of malathion (organophosphate) on acetylcholinesterase.
Dr. Rubio
METABOLIC

RATE-LIMITING ENZYME
PATHWAY
Glycolysis Phosphofructokinase-1 (PFK-1)
Gluconeogenesis Fructose-1,6-bisphosphatase
TCA cycle Isocitrate dehydrogenase
Glycogenesis Glycogen synthase
Glycogenolysis Glycogen phosphorylase
Glucose-6-phosphate dehydrogenase
HMP shunt
(G6PD)
Carbamoyl phosphate synthetase II
Pyrimidine synthesis
(CPS-II)
Purine synthesis Glutamine-PRPP amidotransferase
Carbamoyl phosphate synthetase I
Urea cycle
ENZYME INHIBITORS (CPS-I)
https://qrs.ly/sye03ew Fatty acid synthesis Acetyl-CoA carboxylase
Beta-oxidation Carnitine acyltransferase I

Ketogenesis HMG-CoA synthase
To understand enzyme inhibitors better, please watch the prepared videos! Cholesterol synthesis HMG-CoA reductase

Dr. Rubio

9.7 CLINICAL CORRELATES
9.5 REGULATION OF ENZYME ACTIVITY ENZYMES IN CLINICAL DIAGNOSIS
• The rates of most enzymes are responsive • The presence of elevated enzyme activity in the plasma may
Change in to changes in substrate concentration,
indicate tissue damage that is accompanied by increased release
substrate because the intracellular level of many of intracellular enzymes
concentration substrates is in the range of the Km
• May be useful in evaluating the prognosis of the patient
• Time required: IMMEDIATE
• The lack of tissue specificity limits the diagnostic value of
• Allosteric enzymes are regulated by many plasma enzymes
molecules called effectors that bind non-
covalently at a site other than the active site PRINCIPAL SERUM ENZYMES USED IN CLINICAL DIAGNOSIS
• Positive effectors: increases enzyme
SERUM ENZYME MAJOR DIAGNOSTIC USE
activity
Allosteric Aminotransferases
• Negative effectors: decreases enzyme
enzymes Aspartate aminotransferase Myocardial infarction
activity
(AST/SGOT) (non-specific)
• Allosteric enzymes frequently catalyze the
Alanine aminotransferase
committed step in a metabolic pathway Viral hepatitis
(ALT/SGPT)
(often the rate-limiting step)
• Time required: IMMEDIATE Amylase Acute pancreatitis
Muscle disorders and
• Phosphorylation vs. Dephosphorylation Creatine kinase
Covalent myocardial infarction
• Time required: IMMEDIATE TO MINUTES
modification γ-glutamyl transferase Various liver diseases
• See image below
Lactate dehydrogenase
Liver diseases
isozyme 5
β-glucocerebrosidase Gaucher disease
Alkaline phosphatase Various bone disorders,
(isozymes) obstructive liver diseases
Note: Many of the above enzymes are not specific to the diseases listed
From Harper’s Illustrated Biochemistry. 30th edition


The phosphate molecule acts like a switch, which turns enzymes either on
or off. Some enzymes are active when phosphorylated, others when they
are dephosphorylated. And vice-versa.

Dr. Rubio

Induction and • Enzymes are often those that are needed at

repression of only one stage of development or under
enzyme selected physiologic conditions
synthesis • Time required: HOURS TO DAYS

This regulation happens during transcription.

Dr. Rubio

10. DIGESTION & ABSORPTION OF

MACRONUTRIENTS
1. Digestion & Absorption of Proteins
2. Digestion & Absorption of Carbohydrates
3. Digestion & Absorption of Lipids

10.1 DIGESTION & ABSORPTION OF PROTEINS
PROTEIN DIGESTION IN THE STOMACH
• When gastric secretion is activated by signals coincident with
the ingestion of a meal, pepsinogen is released from chief cells:

At acidic pH in the stomach, pepsinogen is

Pepsinogen
autocatalytically cleaved to yield its active
→ pepsin
enzyme, pepsin
Action of Converts proteins → partially digested
pepsin proteins + oligopeptides

PROTEIN DIGESTION IN THE SMALL INTESTINE LUMEN
10.2 DIGESTION & ABSORPTION OF
• On moving into the small intestine, presence of proteins in the
lumen allows the release of enterokinase (found in the brush
CARBOHYDRATES
border of small intestinal epithelial cells) DIGESTION OF STARCH
• Moreover, inactivated pancreatic proenzymes are released into • Initiated in the oral cavity via the action of salivary amylase (or
the lumen of the small intestine ptyalin)
Action of Enterokinase converts trypsinogen → o Salivary amylase is not essential in starch digestion
enterokinase trypsin o But it may assume greater importance in neonates or patients
Trypsin cleaves the rest of the w/ impaired output of pancreatic enzymes
Activation of inactivated pancreatic proenzymes → • Major digestion in the small intestine via the action of
pancreatic pancreatic proteases (including itself, pancreatic amylase

proenzymes chymotrypsin, elastase, carboxypeptidase • Hydrolyzes internal α-1,4 bonds of

A, carboxypeptidase B) Action of straight chains
amylase • Cannot hydrolyze external bonds nor α-1,6
bonds that form branch points

BRUSH BORDER CARBOHYDRATE HYDROLASES
• Completes the digestion of carbohydrates → monosaccharides
SPECIFICITY OF
PRODUCTS
ENZYMES

Conversion of Inactivated Pancreatic Proteases into Active Enzymes • α-1,4 bonds of maltose
• Glucose
From Berne & Levy Physiology, 7th edition Sucrase • Maltotriose

• Fructose
ACTIONS OF PANCREATIC PROTEASES • Sucrose
• Endopeptidase: cleaves proteins only at internal bonds within • α-1,4 bonds of maltose
the peptide chain • Maltotriose
Isomaltase • Glucose
• Ectopeptidase: cleaves single AAs from the end of a peptide chain • α-1,6 bonds of α-limit
Trypsin Endopeptidase specific at sites of basic AAs dextrins
Chymotrypsin Endopeptidases specific at sites of • α-1,4 bonds of maltose
Elastase neutral AAs Glucoamylase • Glucose
• Maltotriose
Carboxypeptidase Ectopeptidase specific at neutral AA at • Glucose
A C-terminus Lactase • Lactose
• Galactose
Carboxypeptidase Ectopeptidase specific at basic AA at C-
B terminus UPTAKE OF MONOSACCHARIDES
• Only monosaccharides can be absorbed by enterocytes
PROTEIN DIGESTION AT BRUSH BORDER
• Enterocytes express aminopeptidases and
carboxypeptidases that generate products suitable for uptake
at the apical membrane

UPTAKE OF PEPTIDES AND AMINO ACIDS
• AAs and peptides can be absorbed by enterocytes

Amino acid transport Allows uptake of specific amino

proteins acid class
Allows uptake of dipeptide and
Peptide transport tripeptides
protein (peptide Peptides are largely digested in

transporter 1) the cytosol → constituent AAs for Absorption of Monosaccharides
export to the body From Berne & Levy Physiology, 7 edition
th

TRANSPORTERS OF THE LUMINAL SIDE OF ENTEROCYTES
SGLT1 Absorbs glucose or galactose
GLUT5 Absorbs fructose

TRANSPORTERS OF THE BASEMENT MEBRANE SIDE OF
ENTEROCYTES
Releases glucose, galactose, fructose →
GLUT2
bloodstream

Peptide Uptake
From Berne & Levy Physiology, 7th edition
10.3 DIGESTION & ABSORPTION OF LIPIDS 11.2 HIGHLIGHTS OF THE 2018 ENNS, 2015
FUNCTIONS OF ENZYMES INVOLVED IN LIPID DIGESTION UPDATING DIETARY SURVEY, 2020 RNAS
• Released from chief cells Latest dietary survey data were included in the 2015 Updating Dietary
• Not capable of hydrolyzing the 1st and 2nd Survey. No dietary survey data were included in the 2018 ENSS.

Gastric lipase position of the TAG ester → molecule The term “overall” used in the succeeding discussion means “the most
cannot be broken down into components common ____ across all households in the country (urban or rural)”

that can be absorbed into the body I recommend to focus on the following component surveys:
• Capable of hydrolyzing the 1st and 3rd Socioeconomic Survey, Anthropometric Survey, Biochemical Survey,
positions of TAG → free fatty acids + 2- Maternal Health And Nutrition Survey, Infant And Young Child
Pancreatic
monoacylglycerides (2-MAG) Feeding Survey, Dietary Survey
lipase Dr. Rubio
• Inhibited by bile acids, but colipase
PART I – SOCIOECONOMIC SURVEY (2018)

bridges bile acids to lipase
PREFERRED FUEL USED FOR COOKING
• Bridging molecule that binds to bile acids
OVERALL preferred fuel used Liquefied petroleum gas
and to lipase
Colipase for cooking (LPG)
• Anchors lipase to the oil droplet even in
Preferred fuel used for cooking
the presence of bile acids Wood
in RURAL households
Phospholipase
• Hydrolyzes phospholipids Preferred fuel used for cooking Liquefied petroleum gas
A2
in URBAN households (LPG)
Cholesterol • Hydrolyzes cholesterol esters →
esterase cholesterol + free fatty acid MAIN SOURCE(S) OF WATER

Source of drinking water Bottled or mineral
EMULSIFICATION AND SOLUBILIZATION OF LIPIDS
(overall, urban, rural setting) water
• Emulsification of products of lipolysis via bile acids that
Own use faucet from
facilitates the formation of micelles OVERALL source of water for
community water
o Bile acids are synthesized by the liver cooking and handwashing
system
o Serve as biological detergents
Source of water for cooking and
Review: Vitamins ADEK are also transported in these micelles Shared tubed or piped
handwashing in RURAL
Dr. Rubio deep well
households

UPTAKE OF LIPIDS AND SUBSEQUENT HANDLING

Source of water for cooking and Own use faucet from
• Products of lipolysis are directly absorbed by enterocytes due to
handwashing in URBAN community water
their lipophilicity (fat-loving nature or hydrophobicity)
households system
• Unlike monosaccharides and AAs, products of lipolysis are re-
esterified → triglycerides, phospholipids, cholesterol esters PART II – ANTHROPOMETRIC SURVEY (2018)

o This process occurs in the SER of the enterocytes Most vulnerable group affected Children under-five
• Concurrently, apolipoproteins are being synthesized in the by malnutrition years of age
RER of enterocytes Most crucial time to meet the First 1000 days (from
• The re-esterified lipid products + apolipoproteins will form nutritional needs to support mother’s conception
chylomicrons, which consists of: optimum height, growth and until the 2nd birthday
o Lipid core (re-esterified lipid products) mental development of the child)
o Coat by apolipoproteins Mean weight of children under-
11.8 kg
• Chylomicrons are exported from the enterocyte to the lacteals five years
via exocytosis → lymphatics → thoracic duct → blood circulation Mean height of children under-
85.8 cm
Fate of Glycerol released in the intestinal lumen → five years
glycerol absorbed into the hepatic portal vein Percentage of children under-
3 out of 10 children

five years with STUNTING or had
Review: As mentioned in the previous modules, small- and medium- (30.3%)
suffered chronic malnutrition
chain fatty acids can be absorbed directly into the circulation (without
going to the lymphatic system) due to its relative water solubility!
Percentage of children under- 0.5 out of 10 children

Dr. Rubio five years with WASTING (5.6%)

Percentage of children under-
11. EXPANDED NATIONAL NUTRITION 0.4 out of 10 children
five years with OVERWEIGHT-
(4.0%)
SURVEY (ENNS)
FOR-HEIGHT STATUS
1. Background of the Expanded National Nutrition Survey (ENNS) PART III – BIOCHEMICAL SURVEY (2018)
2. Highlights of the 2018 Expanded National Nutrition Survey (ENNS),
2015 Updating Dietary Survey, 2020 Rapid Nutrition Assessment Most prevalent micronutrient
Iron
Survey (RNAS) deficiency in the Philippines

ANEMIA
11.1 BACKGROUND OF THE ENNS
Most common cause of anemia
EXPANDED NATIONAL NUTRITION SURVEY (ENNS) Iron deficiency
globally
• Serves as the banner activity of the Food and Nutrition 11.3%
Research Institute (FNRI) of the Department of Science and Overall anemia prevalence in
(mild public health
Technology (DOST) of the Philippines the Philippines
concern)
• Aims to collect data from the following nine (9) components: Anemia is most prevalent in this 6 months to less than 1
• Socioeconomic survey population group year old
• Anthropometric survey
• Biochemical survey IODINE DEFICIENCY

• Clinical and health survey Major cause of preventable
Iodine deficiency
Nine (9) • Dietary survey mental retardation worldwide
components • Maternal health and nutrition survey Method used to assess the
Urinary iodine
of 2018 ENNS • Infant and young child feeding practices iodine status of the different
concentration (UIC)
survey population groups
Definition of insufficient iodine
• Food security survey
intake in school-aged children <100 ug/L UIC
• Government program participation
(6 years or older) and adults
survey
Definition of insufficient iodine
• Performs national surveys every 5 <150 ug/L UIC
intake in pregnant women
years (2008, 2013, 2018)
Methodology Definition of insufficient iodine
• Performs updating surveys between
intake in lactating women and <100 ug/L UIC
national surveys (2011, 2015, 2020)
children aged <2 years
VITAMIN A DEFICIENCY PART VIII – GOVERNMENT PROGRAM PARTICIPATION
Leading cause of preventable SURVEY (2018, 2020)
Vitamin A deficiency
blindness in children Percentage of Filipino
Preschool-aged children households still experiencing 53.9%
Vitamin A deficiency is most (PSAC), mainly 1 year food insecurity (2018)
prevalent in this population old Percentage of Filipino
group (aged 6 months to 5 households still experiencing 62.1%
years) food insecurity (2020)
16.9%
Prevalence of vitamin A The increase in food insecurity is most likely due to the ongoing
(moderate public health pandemic T Y
X
W
V
U
deficiency in PSAC
concern)
Dr. Rubio
Young children, Women PART IX – DIETARY SURVEY (2015)

Population groups vulnerable to
of reproductive age, Rice-vegetable-fish
vitamin A deficiency Typical Filipino diet
Elderly combination
Major source of vitamin A Whole chicken egg Most commonly consumed food Cereals and cereal
GROUP in the Filipino household products (43.2%)
PART IV – CLINICAL AND HEALTH SURVEY (2018) Most commonly consumed food
Rice and rice products
By occupation, this group had Plant and machine ITEM in the Filipino household –
(94.6%)
the highest prevalence of operators and urban and rural
elevated blood pressure assemblers 1230 grams per
Mean weight of rice consumed
Number of current smokers household (eaten at
4 out of 100 per household
among adolescents least twice a day)
Number of adolescents who Rice and rice products >
3 out of 100 Most common food items
stopped smoking Coconut oil > Coarse
consumed in the household
Number of adolescents who are salt
4 out of 5 Most of Filipinos consume food Snack time > Lunch >
physically inactive
during this period Dinner > Breakfast
PART V – MATERNAL HEALTH AND NUTRITION SURVEY (2018) Food item with the greatest
Number of pregnant Filipino share of energy and nutrient Rice and rice products
women who are nutritionally at- intake
risk of delivering LBW infants 1 out of 5 Energy, Protein,
Rice and rice products are the
and other pregnancy Carbohydrates, Iron,
main contributors for the
complications Thiamine, Riboflavin,
following nutrients:
Number of pregnant Filipino Niacin, Calcium
women taking micronutrient 3 out of 4 Aside from rice and rice
supplements products, calcium is mainly Fish and fish products
Most widely used micronutrient Iron supplements supplied by this food group
supplement among expectants (80.8%) Meat and meat products
Vitamin A is mainly supplied by
Urinary tract infection > (mainly whole
Major pregnancy complication this food group
Hypertension > chicken eggs)
among pregnant Filipino women Vitamin C is mainly supplied by
Diabetes Vegetables > Fruits
Percentage of mothers that this food group
were knowledgeable about 2 out of 3
proper duration of exclusive (62.1%)
breastfeeding END OF BIOCHEMISTRY – MAIN LECTURE PART 1

PART VI – INFANT AND YOUNG CHILD FEEDING SURVEY (2018)
Number of Filipino women
54.9%
using exclusive breastfeeding
IMPORTANT LEGAL INFORMATION
Number of Filipino women

continuing breastfeeding up to 1 50.6% The handouts, videos and other review materials, provided by Topnotch Medical Board
year Preparation Incorporated are duly protected by RA 8293 otherwise known as the
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Mean duration for any type of
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breastfeeding
Most common form of feeding DISCLOSURE

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materials are not photocopied or in any way reproduced, shared or lent to any person or
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PART VII – FOOD SECURITY SURVEY (2018, 2020) person whose name does not appear therein shall be prima facie evidence of violation of RA
8293. Topnotch review materials are updated every six (6) months based on the current
Percentage of Filipino trends and feedback. Please buy all recommended review books and other materials listed
households still experiencing 53.9% below.
food insecurity THIS HANDOUT IS NOT FOR SALE!
Percentage of Filipino
households NEVER or RARELY 7 out of 10
worrying about obtaining the (71.5%)
next meal to eat
Borrowing money from
Major coping strategy of
relatives (2018),
households experiencing food
Purchased food on
insecurity
credit (2020)

Glutamate → Valine at the
APPENDIX: Defect in sickle cell disease 6th position of the beta-
BOARD CORRELATES & QUICK REVIEW globin
1. Structure of Amino Acids & Proteins Glutamate → Lysine at the
2. Structure of Carbohydrates Defect in hemoglobin C disease 6th position of the β-
3. Structure of Lipids globin
4. Structure of Nucleotides Hemoglobin Bart composition 4 gamma-globin
5. Nutrition Hemoglobin H composition 4 beta-globin
6. Vitamins & Minerals Oxygen dissociation curve of
Hyperbolic
7. Genetic Disorders by Chromosome myoglobin
8. Cofactors & Associated Enzymes Oxygen dissociation curve of
Sigmoidal
9. Important Concepts in Medical Biochemistry hemoglobin
10. Miscellaneous Concepts Most abundant protein in the body Collagen
Most common form of collagen in
Type I collagen
the body
1. STRUCTURE OF AMINO ACIDS & PROTEINS Type of collagen present in early
Type III collagen
Most abundant organic molecule wound repair
Proteins
in the HUMAN BODY Type of collagen in late wound
Type I collagen
Enantiomer of amino acids seen in repair
L-isomer
the human body Defective step of collagen synthesis
Hydroxylation step
An imino acid Proline encountered in scurvy
AA with the smallest side chain, Defective step of collagen
only achiral amino acid among the synthesis encountered in Formation of triple helix
Glycine
20 AAs; Used in the first step of osteogenesis imperfecta
heme synthesis Defective step of collagen Cross-linking step
Valine synthesis encountered in Menkes (dysfunction in copper-
Accumulated AAs in maple syrup
Leucine disease requiring lysyl oxidase)
urine disease (MSUD)
Isoleucine Most common form of EDS Hypermobility EDS
AA with the largest side chain Tryptophan Most serious form of EDS Vascular EDS
Known as the 21st AA Selenocysteine Most common type of collagen
Type III collagen
Known as the 22nd AA; restricted affected in EDS
only in some methanogenic Pyrrolysine Defective type of collagen in
archaea and bacteria Type VII collagen
dystrophic epidermolysis bullosa (DEB)
Only semi-essential AA Arginine Defective structure in Marfan
Fibrillin
Cysteine syndrome
Sulfur-containing amino acids
Methionine Skeletal changes
Phenylalanine Aortic dilatation
AAs with aromatic structures Tyrosine Upward and outward
(benzene rings) Tryptophan Triad of Marfan syndrome dislocation of the lens
Histidine (vs downward and inward
Most basic AA Arginine dislocation of the lens in
Most acidic AA Aspartic acid homocystinuria)
First ever sequenced protein Insulin Main cell that synthesizes Plasma cells
First discovered hormone Secretin antibodies or Igs (derived from B cells)
Most common secondary Fragment of Ig containing the
Alpha-helix Fab
structure antigen-binding site
Secondary structure seen in Fragment of Ig containing the
abnormal prion protein (PrP Sc) complement-binding site and Fc
Beta-sheets macrophage-binding site
and Alzheimer disease
histopathology Responsible for determining the
Heavy chains
AAs that can disrupt the alpha- Proline isotype of class of Ig
helix structure Glycine Most abundant light chain in
Kappa chain
The only structure of proteins not humans
Primary structure
affected by denaturation Proteins containing light chains
Reading of amino acid sequences; From N-terminus (NH3 and can be found in the urine of Bence-Jones protein
Order of amino acid sequence end) to patients with multiple myeloma
synthesis C-terminus (COOH end) Most abundant Ig in the BODY
IgA
Amino acid terminus containing (which includes mucous membranes)
N-terminus
targeting signals Most abundant Ig in SERUM IgG > IgA > IgM > IgD, IgE
Amino acid terminus containing Cleaves Ig into 3 parts Papain
C-terminus
retention signals Cleaves Ig into 2 parts Pepsin
Amino acid terminus allowing Refers to the part of the ANTIGEN to
Epitope
protein to be inserted into a which an antibody binds
C-terminus
membrane without having a Refers to the part of the ANTIBODY
Paratope
transmembrane domain that binds to the epitope of the antigen
Number of pyrrole rings in a
Four
porphyrin
Structure of pyrrole rings Aromatic structure
2. STRUCTURE OF CARBOHYDRATES
Bridge formed between pyrrole Methenyl or methyne Most abundant organic molecule in
Carbohydrates
rings in a porphyrin bridges NATURE
Maximum absorption spectrum of 400 nm (known as the Main storage form of
Glycogen
porphyrins Soret peak) carbohydrates in humans
Heme is a metalloporphyrin Building block of all carbohydrates Monosaccharides
Iron This bond links sugar units or
containing this metal Glycosidic bonds
Amino acid serving as the monosaccharides together
biosynthetic precursor to Glycine Most predominant sugar in the
porphyrins human body; Glucose
Most common form of hemoglobin Universal fuel of fetus
Hemoglobin A1
after birth
Location of alpha-globin genes Chromosome 16
Location of beta-globin genes Chromosome 11
TOPNOTCH MEDICAL BOARD PREP BIOCHEMISTRY HANDOUT (PART 1) BY FRINZ MOEY C. RUBIO, MD Appendix
Brain This is the bond formed between
Renal medulla pentose sugar and phosphoryl Ester bond
Tissues which use glucose as its Cornea group of a nucleotide
main metabolic fuel Retina This bond allows the addition of
Testis more phosphoryl bonds at
Anhydride bond
RBCs nucleotides to form di- and
Major constituent of starch (80%) Amylopectin triphosphates
Most stable conformation of Most abundant free nucleotide in Adenosine triphosphate
Chair conformation
glucose mammalian cell (ATP)
Sucrose Nucleic acids are polymers of
Common non-reducing sugars 3’-5’ phosphodiester
Trehalose nucleotides that are joined by this
bond
2nd epimer of glucose Mannose bond
3rd epimer of glucose Allose Sequence of writing the bases of a
From 5’ end → 3’ end
4th epimer of glucose Galactose DNA
More common enantiomer of Determinant of the melting point
D-isomer Number of G-C bonds
carbohydrates of DNA
Among the glucose transporters, Orientation of DNA strands Antiparallel
this is the only transporter that States that the number of purines
GLUT4 Chargaff’s rule
requires insulin (insulin- = number of pyrimidines
dependent) All types of DNA are right-handed
Z-DNA (left-handed)
All glucose transporters utilize except this type of DNA
facilitated diffusion, except for Most common form of DNA
SGLT1/2
this transporter(s) which use(s) physiologically (well-hydrated and B-DNA
secondary active transport w/ low salt concentration)
This glucose transporter allows the Type of DNA found in low
GLUT5
transport of fructose humidity and high salt A-DNA
This carbohydrate is responsible concentration
Fructose
for sperm motility Type of DNA mostly seen in 5’ end
Z-DNA
of chromosomes
3. STRUCTURE OF LIPIDS
Most abundant chromatin protein Histone
The only class of FA that is an Histone seen in the linker region H1
exception to the chylomicron-
Short chain FA (SCFA) Composition of the histone
mediated transportation of fatty Pairs of H2A, H2B, H3, H4
Medium chain FA (MCFA) octomer (core histones)
acids from the intestines to the
Source of negative charge of DNA Phosphate groups
circulation
Source of positive charge of Lysine (H3, H4)
FA that serves as important source
Short chain FA (SCFA) histones Arginine (H2A, H2B)
of energy for the colonic mucosa
Represents the “beads on a string”
Linoleic acid
Essential fatty acids appearance on electron 10-nm chromatin fibril
α-Linolenic acid
microscopy
Semi-essential fatty acid, derived
Arachidonic acid DNA is wrapped by around the
from LINOLEIC ACID 1.75 times
histone octomer by this amount
Class of FA that can decrease the
Condensation of DNA to form
risk for CVD, and reduce the ω-3 series
chromosomes occur during this Prophase
tendency for platelet aggregation
phase of mitosis
ω-3 FA important for the
Cervonic acid (docosa- The highly condensed chromatin
development of fetal brain and
hexaenoic acid) (DHA) seen in electron microscopy, Heterochromatin
retina
which is transcriptionally inactive
Serves as the main storage form of
Triacylglycerol The less condensed chromatin
lipids in the body
seen in electron microscopy, Euchromatin
This lipoprotein has the largest
which is transcriptionally active
diameter, lowest density, highest Chylomicron
Most heterogeneous RNA mRNA
TAG content
Most abundant RNA rRNA
This lipoprotein has the highest
LDL RNA containing significant
cholesterol content
proportions of nucleosides with tRNA
This lipoprotein has the highest
HDL unusual bases
protein content
snRNA
Important steroid in animal cell
Cholesterol RNAs responsible for gene miRNA
membranes
expression regulation siRNA
Important steroid in fungal cell
Ergosterol lncRNA
membranes
Storage form of cholesterol Cholesteryl esters 5. NUTRITION

Primary bile acids synthesized by Cholic acid
This anthropometric measure is
the liver Chenodeoxycholic acid Weight-for-height/length
the best indicator for WASTING
Cholic acid → Deoxycholic
Secondary bile acids resulting This anthropometric measure is
acid Height/length-for-age
from bacterial degradation in the the best indicator for STUNTING
Chenodeoxycholic acid →
colon Cause of marasmus Caloric deprivation
Lithocholic acid
Enzyme responsible for Protein deprivation >
Cause of kwashiorkor
Aromatase caloric deprivation
converting androgens to estrogens
Favored measurement of
Waist circumference
4. STRUCTURE OF NUCLEOTIDES abdominal obesity
(1) Estimated Average
Adenine
Nitrogen bases present in both Requirement,
Guanine
DNA and RNA (2) Recommended
Cytosine Four components of Dietary
Dietary Allowance,
Nitrogen bases present in DNA Reference Intakes (DRI)
Thymine (3) Adequate Intake,
only
(4) Tolerable Upper
Nitrogen base present in RNA only Uracil Intake Level
Methylation of uracil makes this This component of DRI is useful in
Thymine
nitrogen base estimating the actual
This is the bond formed between Estimated Average
requirements in groups &
nitrogenous base and pentose N-glycosidic linkage Requirement (EAR)
individuals; serves as the
sugar of a nucleoside foundation for setting the RDA
This component of DRI refers to Endogenous synthesis
the average daily nutrient intake from 7-
Major source of vitamin D
level that is sufficient to meet the Recommended Dietary dehydrocholesterol via
requirements of nearly all (97- Allowance (RDA) ultraviolet ray B (UVB)
98%) individuals in a particular This form of vitamin K is mainly Phylloquinone
life stage and sex group derived from dietary sources (Vitamin K1)
This component of DRI is set This form of vitamin K is
Menaquinone
instead of an RDA if sufficient synthesized by intestinal bacterial
Adequate Intake (AI) (Vitamin K2)
scientific evidence is not available flora
to calculate an EAR or RDA This form of SYNTHETIC, WATER-
Menadione
This component of DRI refers to SOLUBLE vitamin K is found in
(Vitamin K3)
the highest average daily nutrient supplements
intake level that is likely to pose Tolerable Upper Intake Vitamin K
no risk of adverse health effects to Level (TUL or UL) These vitamins are synthesized by
Biotin
almost all individuals in the intestinal microflora
Vitamin B5
general population This vitamin can be derived from
Carbohydrates: 4 kcal/g Niacin
tryptophan
Amount of energy stored per gram Proteins: 4 kcal/g This is the only water-soluble vitamin Cobalamin
of food constituent Fats: 9 kcal/g not derived from plant sources (Vitamin B12)
Alcohol: 7 kcal/g Most prevalent form of carotenoid β-carotene
Component of TEE with the Resting metabolic rate Carotenoid used to protect against
highest contribution in percentage (RMR) Lutein
macular degeneration
Component of TEE with the Carotenoid used to protect against
Physical activity Lycopene
greatest variation prostate cancer
Carbohydrates: 45-65% Vitamin A deficiency can lead to
Current recommended AMDR Fats: 20-35% Squamous metaplasia
this form of metaplasia in GI and
Protein: 10-35% (columnar → squamous)
respiratory tracts
Type of dietary lipid that generally Most common vitamin deficiency
INCREASES LDL, DECREASES Saturated fatty acids, worldwide;
HDL; Increases incidence of Trans fatty acids Vitamin A deficiency
Most common cause of
coronary artery disease preventable blindness worldwide
Type of dietary lipid that Mono-unsaturated fatty Earliest sign of vitamin A Loss of sensitivity to
DECREASES LDL, INCREASES HDL acids (MUFA) deficiency green light
Type of dietary lipid that ω-6 Poly-unsaturated Earliest symptom of vitamin A Nyctalopia
DECREASES BOTH LDL & HDL fatty acids (PUFA) deficiency (night blindness)
Type of dietary lipid that Most abundant form of vitamin D
suppresses cardiac arrhythmias, in blood circulation; 25-hydroxy (OH)-
ω-3 Poly-unsaturated
reduces plasma TAG, decreases Analyte used in determining the cholecalciferol
fatty acids (PUFA)
risk for thrombosis, lowers blood vitamin D status of the patient
pressure 1,25-(OH)2-
AMDR of added sugars (simple Most biologically active form of
<10% of total kcal cholecalciferol
sugars) vitamin D
(Calcitriol)
This simple sugar is associated Inactive form of vitamin D which
with the development of dental Sucrose 24,25-(OH)2-
is produced by the kidneys when
caries cholecalciferol (Calcitroic
there is high level of Ca2+ in
The FDA standard used for acid)
PDCAAS circulation
measuring protein quality Vitamin D can be used to prevent Mycobacterium
Animal protein sources with a infections caused by this agent tuberculosis
Eggs, milk
PDCAAS value of 1.0 Colon cancer
Plant protein sources with a Vitamin D has antiproliferative
Soybean protein Breast cancer
PDCAAS value of 1.0 effects against these cancers
Prostate cancer
Relationship between nitrogen 1 g nitrogen = Vitamin D deficiency presentation
and protein 𝟔. 𝟐𝟓 𝐠 𝐩𝐫𝐨𝐭𝐞𝐢𝐧 in children BEFORE closure of Rickets
Primary hormonal stimulus for epiphysis
Prolactin
lactogenesis Vitamin D deficiency presentation
Responsible for expulsion of milk in children AFTER closure of Osteomalacia
Oxytocin
into the lactiferous sinuses epiphysis
Secretion of colostrum by the Vitamins and minerals with Vitamin A, Vitamin C,
alveolar cells of the breast begin at 12th – 16th AOG antioxidant properties Vitamin E, Zinc, Selenium
this age Most powerful naturally occurring
Virtually absent nutrient in breast Vitamin E
Vitamin K antioxidant
milk High levels of Vitamin E may
Nutrient with low level in breast interfere with the effects of this Vitamin K
Vitamin D
milk vitamin

Form of Vitamin K from dietary sources Phylloquinone
6. VITAMINS & MINERALS Form of Vitamin K synthesized by
Menaquinone
Major site of storage of fat-soluble bacterial flora
Liver
vitamins in the body Form of Vitamin K, synthetic
Menadione
Liver cell responsible for vitamin (artificial), water-soluble
Stellate cells of Ito
A storage and liver fibrosis when This enzyme is absent in humans and
(perisinusoidal space)
activated other primates causing inability to Gulonolactone oxidase
Storage period of vitamin A in the convert glucose to vitamin C
6 months
liver Swollen gums
The only 2 water-soluble vitamins Vitamin B9 Poor wound healing
Salient features of scurvy
that is mainly stored in the liver Vitamin B12 Bleeding diathesis
Storage period of vitamin B9 in Corkscrew hair
3-4 months
the body Confusion
Triad of REVERSBLE symptoms
Storage period of vitamin B12 in Ophthalmoplegia
3-4 years seen in Wernicke encephalopathy
the body Ataxia
Richest source of vitamin A and Confabulation
Halibut (fish) liver oil IRREVERSIBLE symptoms seen in
vitamin D Personality changes
Korsakoff syndrome
Richest plant source of vitamin A Carrot Memory loss
Mammillary bodies, Kayser-Fleischer rings seen in
Damaged CNS structures in
Medial dorsal nucleus of Wilson disease are deposited in Descemet membrane
Wernicke-Korsakoff syndrome
thalamus this layer of the cornea
Cheilosis, Autosomal recessive disorder Acrodermatitis
2Cs of vitamin B2 deficiency
Corneal vascularization causing ↓ zinc absorption enteropathica
Conversion ratio of tryptophan to 60 mg tryptophan = Mineral that stabilizes the structure
niacin 1 mg niacin of insulin; Deficiency of this mineral Zinc
Vitamins required in the synthesis Vitamin B2 causes impaired spermatogenesis
of niacin from tryptophan Vitamin B6 Mineral that potentiates the action
Chromium
Effect of niacin to cholesterol Decreases VLDL of insulin
profile Increases HDL Endemic, reversible
Diarrhea cardiomyopathy seen in patients Keshan cardiomyopathy
3Ds of vitamin B3 deficiency Dermatitis with Se deficiency
Dementia Prominent feature of Se toxicity Garlic breath
Classical form of dermatitis seen in Tofu, oregano, dairy products are
Calcium
C3/C4 dermatome area in patients Casal necklace rich in this mineral
with vitamin B3 deficiency
Hartnup disease
Conditions increasing the risk for
Carcinoid syndrome
7. GENETIC DISORDERS BY CHROMOSOME
vitamin B3 deficiency CHROMOSOME SELECTED DISEASES
Isoniazid use
Podagra von Hippel-Lindau disease
Prominent features of vitamin B3 3
Hepatotoxicity Renal cell carcinoma
toxicity AD Polycystic kidney disease (PKD2)
Facial flushing
Gopalan’s burning feet 4 Achondroplasia
Vitamin B5 deficiency causes this Huntington disease
syndrome (nutritional
condition Cri-du-chat syndrome
melalgia) 5
This is the only enzyme needing Familial adenomatous polyposis
Glycogen phosphorylase 6 Primary hemochromatosis
vitamin B6 which is not associated
(for glycogenolysis) Williams syndrome
with amino acid metabolism 7
Toxicity of vitamin B6 Sensory neuropathy Cystic fibrosis
RDA of this vitamin depends on Friedreich ataxia
Vitamin B6 9
protein intake Tuberous sclerosis (TSC1)
Substance found in raw egg whites Wilms tumor
(and in some antibiotics) that Beta-thalassemia
Avidin 11
avidly binds to biotin → functional Sickle cell disease
deficiency MEN1
Site of vitamin B9 absorption Jejunum Patau syndrome
Site of vitamin B12 absorption Ileum Wilson disease
13
Vitamin B12 deficiency: Retinoblastoma
Laboratory parameter that BRCA2-associated disorders
↑ methylmalonic acid
distinguishes vitamin B12 Prader-Willi syndrome
Vitamin B9 deficiency:
deficiency from vitamin B9 15 Angelman syndrome
Normal methylmalonic
deficiency Marfan syndrome
acid
Folic acid supplementation to AD Polycystic kidney disease (PKD1)
pregnant women with NO 16 Alpha-thalassemia
400 ug Tuberous sclerosis (TSC2)
HISTORY OF OFFSPRING WITH
NTDs Neurofibromatosis type 1
Folic acid supplementation to 17 BRCA1-associated disorders
pregnant women with HISTORY 4000 ug TP53-associated disorders
OF OFFSPRING WITH NTDs 18 Edwards syndrome
Salivary protein that binds to Haptocorrin 21 Down syndrome
freed vitamin B12 in the stomach (transcobalamin I) Neurofibromatosis type 2
22
Stomach protein that binds to DiGeorge syndrome (22q11)
freed vitamin B12 in the Intrinsic factor Fragile X syndrome
duodenum X X-linked agammaglobulinemia
Receptors that allow the Klinefelter syndrome
Cubilin receptors of ileal
endocytosis of vitamin B12-
enterocytes
intrinsic factor complex 8. COFACTORS & ASSOCIATED ENZYMES
Transport protein of vitamin B12 COFACTOR ASSOCIATED ENZYME(S)
Transcobalamin II
in circulation
• Cytochrome oxidase
The site of absorption of iron Proximal duodenum Copper
• Superoxide dismutase (cytosolic)
This form of iron is favored for • Cytochrome oxidase
absorption across the luminal side Ferrous (Fe2+) iron • Catalase
of the enterocytes Iron
• Peroxidase
This vitamin favors the reduction • Tryptophan pyrrolase
Vitamin C
of ferric iron to ferrous iron Potassium • Pyruvate kinase
This protein is responsible for • Hexokinase
transferring iron across the Magnesium • Glucose-6-phosphatase
Ferroportin
basolateral membrane of • Pyruvate kinase
enterocytes to the circulation • Arginase
This form of iron is favored when Manganese • Ribonucleotide reductase
it is being transported in the Ferric (Fe3+) iron • Superoxide dismutase (mitochondrial)
plasma by transferrin Molybdenum • Dinitrogenase
Chief regulator of systemic iron Nickel • Urease
Hepcidin
homeostasis • Carbonic anhydrase
This water-soluble substance serves • Alcohol dehydrogenase
Ferritin Zinc
as an indicator of iron body stores • Carboxypeptidases A and B
This water-insoluble substance • Superoxide dismutase (cytosolic)
Hemosiderin
serves as an index of iron overload • Glutathione peroxidase
Selenium
Cirrhosis • Iodothyronine deiodinase
Classic triad of hemochromatosis Diabetes mellitus
Bronzing
9. IMPORTANT CONCEPTS IN MEDICAL WBC capable of clearing antigen-

antibody complexes (immune Eosinophils
BIOCHEMISTRY complexes)
THYROID HORMONES Complement pathway that is IgG
Classic pathway
PARAMETER T4 T3 or IgM-mediated
Receptor binding 10-10M 10-11M Complement pathway activated by
Relative metabolic potency 0.3 1 microbial surface molecules Alternative pathway
Intracellular hormone fraction 20% 70% (repeating polysaccharides)
Fraction directly from the thyroid 100% 20% Complement pathway activated by
Lectin pathway
Production rate (including 90 ug/day 32 ug/day mannose on microbe surface
peripheral conversion) Complement protein acting as
C3a, C4a, C5a
Serum half-life 7 days 2 days anaphylatoxins
Serum concentrations Complement protein causing
C3b
Total hormone 8 ug/dL 0.14 opsonization
ug/dL Complement protein causing
C5a
Fraction of total hormone in the 0.02% 0.3% neutrophil chemotaxis
unbound form Complement proteins making up
C5b, C6, C7, C8, C9
Unbound (free) hormone 21 x 10- 6 x 10-12M membrane attack complex (MAC)
12M Deficiency in C5-C9 increases risk
Neisseria
for infection by this microbe
INNATE VS. ADAPTIVE IMMUNITY
ADAPTIVE DISORDERS OF ISOLATED HYPERBILIRUBINEMIA
PARAMETER INNATE IMMUNITY Isolated Indirect Hyperbilirubinemia
IMMUNITY
Neutrophils, Uridine diphosphate-
Enzyme allowing conjugation of
Macrophages, glucuronosyl transferase
glucuronic acid to bilirubin
Monocytes, Dendritic (UDPGT)
cells, NK cells, T cells, B cells, UDPGT activity of Crigler-Najjar
Components Type II can be increased by this Phenobarbital
Complement proteins, Immunoglobulins
Physical epithelial drug
barriers, Secreted
enzymes CRIGLER- CRIGLER-
GILBERT
Variation via genetic PARAMETER NAJJAR TYPE NAJJAR TYPE
SYNDROME
recombination during I II
Mechanism Germline encoded
lymphocyte UDPGT 0-10% 10-35% of
0% of normal
development activity of normal normal
Resistance occurs Indirect
>20 mg/dL 6-25 mg/dL <6 mg/dL
through generations bilirubin
Microbial resistance is
Resistance (does not change Prevalence Rarest Uncommon Common
not heritable
within the life of an Prognosis Poorest Poor Better
organism)
Highly specific, refined Isolated Direct Hyperbilirubinemia
over time Defect in Dubin-Johnson
Nonspecific; MRP2 gene mutation
Develops over long syndrome
Response to Rapid response
periods; OATP1B1, OATP1B3 gene
pathogens (minutes to hours); Defect in Rotor syndrome
Memory response if mutations
No memory response
faster and more Pathologic feature of Dubin-
robust Dark liver
Johnson syndrome
Lysozyme,

Secreted Complement, C-
Immunoglobulins 10. MISCELLANEOUS CONCEPTS
proteins reactive protein,
Defensins, Cytokines This is the number of atoms
Toll-like receptors needed to satisfy a macromolecule 1,000 atoms
Receptors that (old definition)
recognize patterns Number of ATP required for the
associated with daily functioning of the body 100-150 mol/L/day
Memory cells
pathogens, known as (mol/L/day)
B and T cells that elicit
Pathogen-Associated Number of ATP required for the
a stronger, quicker
Key features Molecular Patterns
response after a daily functioning of the body 70 kg/day
(PAMPs) → activation
subsequent exposure (kg/day)
of NF-KB
to a trigger Amount of ATP molecules
10 million ATP
PAMPs
utilized by a single cell per
molecules/second
LPS, Flagellin, Nucleic second
acids Requirements of a chemical Reactants, Products,
reaction Energy
Lymphocytes that are part of the Natural killer cells (NK) Metabolic terminology for
Anabolism
innate immunity; destroys tumor cells / Large granular synthesis of compounds
cells and virally infected cells lymphocytes (LGL) Metabolic terminology for
Catabolism
Main pathway used by NK cells in destruction of compounds
Perforin/granzyme
destroying tumor and virally
mechanism

infected cells
Other pathway used by NK cells in
Antibody-dependent cell-
destroying tumor and virally
mediated cytotoxicity
infected cells
Dendritic cells (major),
Cells capable of antigen
Macrophages,
presentation
Langerhans cells, B cells
Placental villous macrophages of
fetal origin present throughout Hofbauer cells
pregnancy

TOPNOTCH MEDICAL BOARD PREP BIOCHEMISTRY HANDOUT

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TOPNOTCH MEDICAL BOARD PREP BIOCHEMISTRY HANDOUT

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TOPNOTCH MEDICAL BOARD PREP BIOCHEMISTRY HANDOUT (PART 1) BY FRINZ MOEY C.

• Please buy the following: CHEMICAL EQUATION

BIOCHEMISTRY PART 1 – Molecular hydrogen reacts with molecular oxygen to yield

4. Structure of Lipids 15 Arrow pointing to the • Represents FORWARD REACTION

Remember this: If the FORWARD REACTION is an exothermic process; Heat transfer by

Heat transfer – air or water – which heat is

• Therefore, if you see a hydrogen atom

OXIDATION & REDUCTION

WATER HAS A HIGH DIELECTRIC CONSTANT

the amide, glycoside, or ester bonds that hold biopolymers

The concept of polarity is very important when we talk about solubility:

Remember: opposites attract! The partially positive end of one water

• Resist a change in pH when protons are produced or consumed

Non-α-amino acids present in tissues in free form are: β-alanine,

2.2 CLASSIFICATION OF AMINO ACIDS

Alanine, Glutamine, Glutamate are important in ammonia disposal in the

VALINE, LEUCINE, ISOLEUCINE

Glutamate is the major excitatory neurotransmitter of the CNS. GABA is

TRYPTOPHAN Glycine is the major inhibitory neurotransmitter of the SPINE.

MNEMONIC TRYPTOPHAN DERIVATIVES

o Involved in transfer of methyl groups as S-adenosylmethionine HISTIDINE, ARGININE, LYSINE

PROLINE o Arginine and lysine are positively charged

• Contributes to the fibrous structure of collagen and interrupts α- HISTIDINE

SERINE, THREONINE, TYROSINE

o Also a precursor for thyroxine and melanin LYSINE

ASPARAGINE, GLUTAMINE CLASSIFICATION OF

Warning: Please take note that in some Biochemistry textbooks, they

Phenylalanine Histidine Tryptophan Trp W (tWiptophan)

Refers to the set of all the proteins expressed by

Form II is the zwitterion for alanine (neutral charge overall). Acidic

N-TERMINUS AND C-TERMINUS

• Salient functions of N- and C-terminus of AA sequences:

TERTIARY STRUCTURE PRION DISEASES

Amyloid plaques & neurofibrillary tangles in Alzheimer disease are

Structural proteins STRUCTURE OF HEME

MNEMONICS BLOOD CELL FORMATION

GLYCATED HEMOGLOBIN (HbA1C)

IN THE EMBRYO • Effect on RBC:

you rely on fetal hemoglobin that doesn’t contain beta chains.

Hemoglobin C disease is benign compared to sickle cell disease because

1. Synthesis of pre-procollagen in the rough endoplasmic

CLASSICAL HYPERMOBILITY VASCULAR

o Hearing loss α-1 ANTITRYPSIN DEFICIENCY

Imagine elastase as if it were scissors that keep on cutting elastin. α-1

2.10 STRUCTURE OF IMMUNOGLOBULINS Mnemonic:

Fab = contains antigen-binding site 5 Pentoses

3.3 PROJECTIONS, PROPERTIES, AND ISOMERISM

In the small intestines, GLUT 2 is found in the basement membrane (2

CLASSIFICATION OF FATTY ACIDS (FA)

DEPENDING ON THE CHAIN LENGTH IMPORTANT FATTY ACIDS

fermentation of dietary carbohydrates ESSENTIAL FATTY ACIDS

DEPENDING ON THE PRESENCE OF DOUBLE BOND Linoleic acid

• Functions of essential fatty acids:

Recall that thromboxane is a derivative of arachidonic acid, an ω-6 FA.

As you increase the protein content of lipoproteins (thereby lowering the

• Also known as triglyceride, neutral fat

• Structure: • Deposition of cholesterol and cholesteryl esters in the artery

4.6 STRUCTURE OF CHOLESTEROL CHOLESTEROL

Nucleotide = (𝐍𝐢𝐭𝐫𝐨𝐠𝐞𝐧𝐨𝐮𝐬 𝐛𝐚𝐬𝐞 + 𝐏𝐞𝐧𝐭𝐨𝐬𝐞 𝐬𝐮𝐠𝐚𝐫) +

Cytosine = present in both DNA & RNA

molecules in purine metabolism)

Familiarize yourself with the “language of the nucleotides”. “Parang love

does not consider posthumous candidacies D H

Glutamate is the major excitatory neurotransmitter of the CNS. GABA is