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APhA CH 5 Biochemistry - Summary

First Part by Pearl Chris


MAJOR GROUPS OF BIOMOLECULES:
1.
2.
3.
4.

Amino acids.
Fatty acids.
Carbohydrates.
Nucleic acids.

These building blocks in turn form major macromolecules:


1.
2.
3.
4.
5.

Proteins and enzymes.


Lipids.
Glycogen and starch.
RNA.
DNA.

Enzymes are primarily catalysts of various reactions needed to carry out1.


2.
3.
4.
5.

Cellular development.
Cell metabolism.
Growth and differentiation.
Cellular regulation.
Cell death (apoptosis).

CHEMISTRY OF BIOMOLECULES:
PROTEINS:

Amino acids building blocks of protein.


All amino acids contain amino group and carboxylic acid group.
Two large groupings of amino acids depending on amine group:
1. Primary nitrogen atom has only one bond to carbon atom.
2. Secondary nitrogen atom is bonded to two carbon atoms.

Nine essential amino acids:


1.
2.
3.
4.
5.
6.
7.
8.
9.

His
Ile
Leu
Lys
Met
Phe
Thr
Trp
Val

10.
They cannot be synthesized from other amino acids or dietary sources.

Adults produce Tyr from Phe and Cys from Met, but infants and young kids cannot. Hence Tyr and Cys are
considered essential in this population. Remaining are nonessential meaning they are synthesized from other
amino acids or metabolic sources.
Many amino acids involved in critical metabolic pathways.
Arginine, ornithine, and citrulline ----> amino acids of urea cycle (ammonia --->urea), which is main pathway
for nitrogen waste product excretion from protein metabolism.
Glutamine, cysteine, and glycine --->tripeptide glutathione (first line cellular antioxidant). Synthesized in all
tissues by two-step enzyme mediated process.
Peptide bond formed between two amino acids is primary element of peptide and protein structure. Bond
formation at cellular level by ribosome and involves several forms of RNA.
Net chemistry of bond formation and hydrolysis:
NH2-CHR1-COOH+NH2-CHR2-COOH<----->NH2-CHR1-CONH-CHR2-COOH+H2O
In bond formation direction, water molecule eliminated.
Bond hydrolysis direction, water molecule inserted.

PROTEIN AND ENZYME STRUCTURE:


Four main elements:

Primary sequence of chain of amino acids.


Secondary first step in folding protein. Local amino acids form two main structures through hydrogen
bond.
1. Alpha helix (hydrophilic amino acids)
2. Beta-pleated sheet (hydrophobic amino acids).
Tertiary complex folding and arrangement of helices and sheets in globular structure held by hydrogen
bonds, ionic interaction, and disulfide bridges. Tertiary structure incorporates non-amino acid
components like metal ions in structure bonded to functional side chain groups.
Quarternary combination of two or more individual protein chains to form multisubunit protein
complex. Formed and maintained by hydrogen bonding and ionic and hydrophobic interactions. This
allows greater regulation in transport (hemoglobin and oxygen delivery) and enzyme activity.

DNA mutation leads to abnormal proteins. Single nucleotide polymorphism (SNP) leads to alteration in
primary amino acid sequence.
Example, sickle cell anemia: Normal adult hemoglobin has glutamic acid at sixth position in beta globin
protein chain. Due to single point mutation (A-T), sickle cell patients have valine at this position. This leads to

sickle shape of RBC (two alpha and two beta globin chains) and blockage in microvasculature called sickle cell
crisis.

Many proteins undergo modification after folding and assembly called post-translational modification.
AMINO ACIDS

MODIFICATION

Ser, Thr, Tyr, Asp

Phosphorylation (on-off switch to regulate


enzymes)

Ser, Thr, Phe, Pro


His, Thr, Glu
Lys, Asp, Pro, Tyr

Glycosylation (cell-cell recognition)


Methylation (histone protein, control DNA
transcription)

Amino terminus

Hydroxylation
crosslinking)

(collagen

formation

and

Carboxyl terminus

Formylation or acetylation (protein synthesis


initiation)
Glycosylphosphatidylinositol (anchor to cell
surface)

Second Part by Renny Akintunde


Carbohydrates
Hexoses (C6H12O6) & Pentoses (C5H10O5) are most common
Provides Energy (short term source)& Structure
Stored in human as Glycogen (major source of energy via nutrition), mostly in Liver & Muscle
Glucose (a hexose)is the product of glycogen hydrolysis
Pentoses make up part of nucleotides in RNA & DNA (nucleic acid)
Glycosylation requires sugar molecules (oligosaccharide)
Involved in post-translational modification of proteins
Glycoproteins & Glycolipids play a major role in cell-cell recognition e.g. Human ABO Blood Groups
(depends on specific glycosylation)
Human ABO Blood Groups have specific Oligosaccharides :
Galactose (Gal)
Fucose (Fuc)
N-Acetyl Galactosamine (N-A-Gal)
N-Acetyl-Glucosamine(N-A-GLu)
o These Oligosaccharides attach to a Ser (Serine) or Thr (Threonine) residue on a protein
o O-blood group = Gal N-A-GLu Gal Fuc
o A-blood group = Gal N-A-GLu Gal Fuc + N-A-GaL
o B-blood group = Gal N-A-GLu Gal Fuc + Gal
o AB-blood group = [Gal N-A-GLu Gal Fuc + N-A-GaL] + [Gal N-A-GLu Gal Fuc +
Gal]
o GalNac transferase adds N-A-GaL to A-blood group (2 copies of same gene expressed)
o Gal transferase adds Gal to B-blood group (2 copies of same gene expressed )
o The two enzymes or protein (Two genes expressed) control the addition of the last carbs.
o AB-blood group express one copy of both genes.
o O-blood group express none of these genes
Fatty Acids & Lipids
Phospholipids or Phosphoglycerides , major component of cell membrane ( a lipid bilayer)
Cellular communication (prostanglandins & Leukotrienes)
Major source of Energy (long-term source)
Esterification of glycerol with fatty acids produces Glyceride or acylglycerols
Glycerol + One fatty acid = Monoglyceride
Glycerol + Two fatty acid = Diglyceride
Glycerol + Three fatty acid = Triglyceride
General Phospholipid structure---> i.e. most common
Glycerol (as backbone)
Fatty Acid (1,2 or 3)
Phosphate group
Amino Alcohol ( i.e. choline, ethanolamine etc)
Amino Alcohol bonds with the phosphate group via ionic bonding, by losing a proton per molecule
Oleic acids, Palmitic acid, Stearic acid are a few examples of Major Fatty Acids of
Glycerolphospholipids
Most phospholipids will have two different fatty acid chains

DNA & RNA


Naturally occurring Polynucleotide (long-chain of many nucleotides bonded via Hydrogen bonding)
A nucleotide unit has 3 main components
Sugar Molecule ( pentose carbohydrate - Ribose )
D-ribose (RNA)
D-2-deoxyribose (DNA)
A Phosphoric acid molecule
A purine or Pyrimidine base molecule
DNA contains (stores) all genetic codes needed to make new cells, tissues, organs or Living Organisms
DNA -----transcription-----> mRNA ----- translation -----> Protein
RNA is essential in protein synthesis types of RNA
mRNA (Messenger RNA)
copied DNA Strand
pre-mRNA consist of introns & Exons
Introns (interval sequence) in a copied DNA strand need to be removed
Exons (expressed sequence composed of codons) in a copied DNA strand fuse to
form the mature mRNA

tRNA (Transfer RNA, involved in translation process)


inverted L structure (T)
3 nucleotide anticodon (compliments to 3 codons on mRNA) is at bottom of
inverted L
Both 5 & 3 ends are the Acceptor stem
The 3 end protrudes with the ACCA sequence, is the site charged with amino
acids for translation
Its 3 OH end is where specific amino acids for that tRNA is added making each
tRNA unique.
rRNA (Ribosomal RNA)
2 two ribosomal sub-units 30s & 50s (small & Large with respect)
Supports the mRNA strand during translation, by moving it along as tRNA
attaches its 3 anticodons to codons on the mRNA to make a long chain of amino
acids ( a specific protein)
siRNA (Small Interfering RNA)
18 25 nucleotides
Interferes with mRNA by preventing translation or promoting degradation
Anti-transcription mRNA
mRNA that binds to single-strand DNA
Preventing transcription.

siRNA & Drug Development

siRNA -->future goal -- to silence or control genes


Problems with development
o Delivery to target tissue due to the vast presence of RNAse systemically.
o Unwanted immune responses may be induced

CPR 7- Ch 8 Functional Group Chemistry and Biochemistry


(This chapter is not present in CPR 8 ed.)

Author = Unknown

Organic chemistry
Functional groups affect hydrophilicity, lipophilicity, reactivity, shelf life, stability, biotransformation,
metabolism.
Alkanes
Also called paraffins, saturated hydrocarbons.
General formula: R-CH2-CH3. Lipid soluble.
Common reactions: halogenation, combustion.
Chemically inert to air, heat, light, acids, bases. Stable in vivo.
Alkenes
Also called olefins, unsaturated hydrocarbons.
General formula: R-CH=CH2. Lipid soluble.
Common reactions: addition of hydrogen or halogen, hydration (to form glycols), oxidation (to form peroxides).
Volatile alkenes and peroxides may explode in presence of O2 and spark
Stable in vivo. Hydration, peroxidation, reduction may occur.
Aromatic hydrocarbons
Based on benzene. Exhibit multicenter bonding. Lipid soluble.
Common reactions: halogenation, alkylation, nitration, sulfonation.
Chemically stable.
In vivo: hydroxylation, diol formation.
Alkyl halides
Halogenated hydrocarbons. General formula: R-CH2-X.
Lipid soluble. degree of halogenation Solubility.
Common reactions: dehyro-halogenation, nucleophilic substitution.
Stable on the shelf. Not readily metabolized in vivo.
Alcohols
Contains OH group. May be primary (R-CH2-OH), secondary (R1/R2-CH-OH), or tertiary (R1/R2/R3-C-OH).

Alcohols are lipid soluble.


Low molecular weight alcohols are water soluble. hydrocarbon chain length water solubility.
Common reactions: oxidation, esterification.
Oxidation: primary alcohol aldehyde acid. Secondary alcohol ketone. Tertiary alcohol not oxidized.
Stable on shelf. In vivo: oxidation, sulfation, glucuronidation.
Phenols
Aromatic compounds containing OH groups directly connected to aromatic ring. Monophenols one OH.
Catechols two OH.
Phenol (carbolic acid): water soluble. ring substitution water solubility. Most phenols are lipid soluble.
Common reactions: with strong bases to form phenoxide ion, esterification with acids, oxidation to form
colored quinones.
On the shelf: oxidation with air or ferric ions.
In vivo: sulfation, glucuronidation, aromatic hydroxylation, o-methylation.
Ethers
General formula: R-O-R.
Lipid soluble. Partially water soluble. hydrocarbon chain water solubility.
Common reaction: oxidation to form peroxides (may explode).
In vivo: o-dealkylation. Stability with size of alkyl group.
Aldehydes
General formula: R-CHO (contains a carbonyl group C=O).
Lipid soluble. Low molecular weight aldehytes are also water soluble.
Common reactions: oxidation (to acids, in vivo and in vitro) and acetal formation.
Ketones
General formula: R-CO-R (contains a carbonyl group C=O).
Lipid soluble. Low molecular weight ketones are also water soluble.
Nonreactive and very stable on the shelf.
In vivo: some oxidation or reduction.
Amines
Contain an amino group (-NH2). Primary (R-NH2), secondary (R1/R2-NH), tertiary (R1/R2/R3-N), quaternary
(R1/R2/R3/R4-N+ X-).
Lipid soluble. Low molecular weight amines water solubility. branching water solubility (primary
amines and most soluble). Quaternary amines (ionic) and amine salts are water soluble.
Common reactions: oxidation (air oxidation on shelf), salt formation with acids. Aromatic amines are basic
reactive with acids.

In vivo: glucuronidatin, sulfation, methylation. 1ry oxidative deaminatin. 12y/2ry acetylation. 2ry/3ry
dealkylation.
Carboxylic acids
General formula: R-COOH (Carboxyl group COOH).
Lipid soluble. Low molecular weight acid and Na/K salts water soluble.
Common reactions: salt formation with bases, esterification, decarboxylation.
Very stable on shelf. In vivo: conjugation (with glucuronic acid, glycine, glutamine), beta oxidation.
Esters
General formula (R-COOR).
Lipid soluble. Low molecular weight esters are slightly water soluble.
Common reaction: hydrolysis to form carboxylic acid and alcohol (in vivo by esterases / in vitro).
Amides
General formula: R-CONH2 or R-CONR1/R2 (lactam form).
Lipid soluble. Low molecular weight amides are slightly water soluble.
No common reactions. Very stable on shelf.
In vivo: enzymatic hydrolysis by amidases in the liver.
Biochemistry
Amino acid and proteins
Monomeric units of protein (peptide bonds). Formula: NH2-CH-R/-COOH. Proteins are made of 20 AA, differ
in R side chain (alpha (C)).
Protein hydrolysis to AAs by acids, bases, enzymes.
AA ionize (depending on pH) to zwitterions structure (NH3+-CH-COO-/R) water solubility, melting point.
Levels of protein structure: primary, secondary (alpha/beta), 3ry, 4ry.
Carbohydrates
Polyhydroxy aldehydes or ketones
Monosaccharides: simple single unit sugars, e.g., glucose, fructose.
Oligosaccharides: short chains of monosaccharides joined covalently, e.g. sucrose (has to convert into glucose,
fructose before GI absorption), maltose (hydrolyzed by maltase into 2x glucose), lactose (milk sugar, has to
convert into galactose, glucose before GI absorption).
Polysaccharides: long chains of monosaccharides, e.g., cellulose, glycogen.
Pyrimidines and purines
Bases bond with ribose nucleosides bond with phosphoric acid nucleotides building blocks of nucleic
acid.
Exhibit tautomerism (isomerism): can be keto or enol.

Pyrimidines bases: cytosine, uracil, thymine.


Purine bases: adenine, guanine
DNA bases: thymine, cytosine, adenine, guanine
RNA bases: uracil, cytosine, adenine, guanine.
Biopolymers
Enzymes
Linked amino acid chains (proteins) catalysts for biological reactions. They reactions activation energy but
do not change reaction equilibrium point, are used up or changed in the reaction. May require cofactors or
coenzymes.
Cofactor: inorganic (metal ion) or nonprotein organic molecule. Prosthetic group: cofactor firmly bound to
apoenzyme (protein portion of a complex enzyme). Coenzymes: organic cofactor that is not firmly bound but
actively involved in catalysis. Holoenzyme: complete catalytically active enzyme system.
Lyases: removes functional group (deaminase, decarboxylase).
Ligases: bind two molecules (e.g. DNA ligase 2 nucleotides).
Isomerases: change DL, cistrans, vice versa.
Polysaccharides
Also called glycans. Long chain polymers of carbohydrates.
Homopolysaccharides: Contains one type of monomeric units. Starch plants reserve food, two glucose
polymers (linear water soluble amylose, and branched water insoluble amylopectin), enzymatic hydrolysis
maltose (glucose disaccharide). Glycogen branched D-glucose chain, polysaccharide storage in animal cells
(liver, muscles). Cellulose water soluble, in plant cell wall, linear D-glucose chain, cant be digested
(hydrolyzed) by humans.
Heteropolysaccharides: contains two or more monomeric units. Heparin acid mucopolysaccharide with
sulfate derivatives, contains glucosamine, in lung tissue, used to prevent clotting. Hyaluronic acid in
bacterial cell wall, virteous humor, synovial fluid, contains glucosamine.
Nucleic acids
Linear polymers of nucleotides pyrimidine and purine bases linked to ribose or deoxyribose sugars
(nucleosides) and bound to phosphate groups.
Phosphodiester bonds: join successive DNA / RNA nucleotides.
DNA: compared to RNA it lacks an OH group and contains T rather than U. (DT, RU).
DNA: two complementary alpha helical strands coiled to form double helix. Hydrogen bonding between
specific base pairs hold the strands together. Hydrophobic bases are on the inside of the helix. Hydrophilic
deoxyribose phosphate on the outside.
Backbone: alternating phosphate and pentose units with a purine or pyrimidine attached to each.
Strong acids associated with cellular cations and basic proteins (histones, protamines).
rRNA (ribosomal): in ribosomes.
mRNA (messenger): the template for protein synthesis specifies the polypeptide amino acid sequence.

tRNA (transfer): carries activated amino acids to ribosomes for incorporation to the growing polypeptide
chain.
Biochemical metabolism
Factors affecting metabolism: substrate concentration, enzymes, allosteric (regulatory) enzymes, hormones,
compartmentation.
Catabolism: degradation reactions that release energy for useful work (e.g. mechanical, osmotic, biosynthetic).
Anabolism: biosynthetic (build-up) reactions that consumer energy to form new biochemical compounds
(metabolites).
Amphibolic pathways: may be used for anabolic or catabolic purposes. Example: Krebs cycle, it breaks down
metabolites to release 90% of the organisms energy, but it also uses metabolites for form compounds such as
AA.
Bioenergetics
Substrate level phosphorylation: forms one unit of ATP per unit of metabolite, no oxygen required.
Oxidative phosphorylation: forms 2 or more ATP per unit of metabolite. Uses oxidoreductase enzymes (e.g.
dehydrogenases) using cofactors NAD (nicotinamide A dinucleotide) or FAD (flavin). Energy released from the
reaction is used to form ATP in the mitochondria.
Carbohydrate metabolism
Catabolism: releases energy from carbohydrates.
Glycogenolysis: breakdown of glycogen into glucose phosphate in the liver, skeletal muscles controlled by
glucagon and epinephrine.
Glycolysis: breakdown of sugar phosphates (e.g. glucose, fructose, glycerol) into pyruvate (aerobically) or
lactate (anaerobically) to produce energy (ATP)
Anabolism: consumes energy to build complex from simple molecules
Glycogenesis: formation of glycogen in the liver and muscles from glucose in diet controlled by insulin.
Gluconeogenesis: formation of glucose from noncarbohydrate sources (e.g. lactate, pyruvate).
Krebs cycle
Location: in the mitochondria. Absent in RBCs (no mitochondria)
Catabolism: converts pyruvate (glycolysis), acetyl CoA (fatty acid degradation) and amino acids into CO2
and water with release of energy. Oxygen dependent (aerobic).
Anabolism: forms amino acids (aspartate, glutamate) and heme ring from metabolites.
Electron transport: accept electrons and hydrogen from oxidation of Krebs cycle metabolites and couples the
energy released to make ATP.
Lipid metabolism
Catabolism
Triglycerides stores in fat cells (adipocytes) are hydrolyzed by hormone-sensitive lipases into three fatty acids
and glycerol

Fatty acids: broken down by beta oxidation to acetyl CoA to Krebs cycle breaks down to CO2, water and
energy release.
Ketogenesis: very rapid break down of fatty acids leading to formation of ketone bodies (as in DM).
Glycerol: enters glycolysis oxidized to pyruvate to Krebs cycle CO2 and water.
Steroids: may be converted to bile acids, vitamin D, hormones.
Anabolism
Fatty acids: formed in the cytoplasm. Unsaturation occurs I the mitochondria or endoplasmic reticulum.
Essential fatty acids: linoleic acid (can not be synthesized, diet is only sources).
Terpenes: derived from acetyl CoA. Include: cholesterol, steroids, fat soluble vitamins (ADEK), bile acids.
Sphingolipids: forms a ceramide backbone with fatty acids. Joins with other compounds to form cerebrosides,
sphingomyelin
Phosphatidyl compounds: i.e. phosphatidyl choline (lecithin), ethanolamine.
Nitrogen metabolism
Catabolism
Amino acids: amino group is removed by transaminase. Carbon skeleton is broken down to acetyl CoA or
citric acid derivatives oxidized to CO2 and water for energy. Glycogenic amino acids form glucose as needed
by guconeogenesis.
Purines: 90% is salvaged, 10% degrade to uric acid using xanthine oxidase.
Pyrimidines: breaks down to B-alanine, ammonia, CO2
Anabolism
Amino acids: from citric acid cycle intermediates. Essential AA: TIM (threonine, isoleucine, methionine),
HALL (histidine, arginine, lysine, leucine), PVT (phenylalanine, valine, tryptophan) PVT TIM HALL
Purines / Pyrimidines: from aspartate, carbamoyl phosphate, CO2, other AA.
Nitrogen excretion
Excess nitrogen is toxic must be eliminated, mainly as urea.
Urea synthesis: in the liver using the Krebs-Henseleit pathway. Amino acid AA transferases
(transaminases) + pyridoxine (vitamin B6) as coenzyme Ammonia + glutamate glutamine + CO2
carbamoyl phosphate urea cycle urea.
Uric acid synthesis: most purines are salvages. Remaining purines are excreted as uric acid.