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Module 5: MTChem2:Biochemistry for MLS

(Lecture)
Nucleic Acid And Protein Synthesis College A.Y. 2021 – 2022 – 2

OUTLINE DIFFERENCE OF RNA AND DNA


I Part 1 • RNA = Ribose ; DNA = no hydroxyl group in the 2nd
A Types of Nucleic Acids
B Nucleosides & Nucleotides
Carbon
C Nucleic Acid Structure • Important Note: the presence of hydroxyl group in the 3rd
D DNA Double Helix and 5th Carbon are important in the formation of nucleic
II Topic 2 acid.
A Central Dogma of Molecular Biology
i Replication NITROGEN-CONTAINING HETEROCYCLIC BASES
ii Transcription
iii Translation (Protein Synthesis) • PYRIMIDINE
B DNA vs RNA o Monocyclic base with a six-membered ring
C Mutations
i Types of Mutations • PURINE
ii Examples o Bicyclic base with fused five and six-membered
rings
NUCLEIC ACID o
• What are nucleic acids?
o Nucleic acids are unbranched polymers composed of
repeating monomers called nucleotides.

DNA RNA
Types Of
(double- (single-
Nucleic Acid
stranded) stranded)

Found in cell All parts of the NITROGENOUS BASES


LOCATION
nucleus cell

Storage and
PYRIMIDINE DERIVATIVES
transfer of Synthesis of
FUNCTION CYTOSINE
genetic proteins
information • 4-amino-2-oxo derivative of pyrimidine
• DNA – Deoxyribonucleic Acid
• RNA – Ribonucleic Acid URACIL
• 2,4-dioxo derivative of pyrimidine
NUCLEOSIDE
• Two subunit molecule THYMINE
o Sugar • 5-methyl-2,4-dioxo derivative of pyrimidine
o Nitrogen-containing bases
▪ PYRIMIDINE
▪ PURINE

• Note on the 4th Carbon: Cytosine has an amino group;


while uracil and thymine have hydroxyl group.
TWO COMPONENTS • Note on the 5th Carbon: Thymine has methyl group while
Uracil has none.
PENTOSE SUGARS • Pneumonic : CUT
• Pentose 2’- deoxyribose
• Ribose — contain five carbons PURINE DERIVATIVES

ADENINE
• 6-amino purine derivative

GUANINE
• 2-amino-6-oxo purine derivative

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MODULE 5: NUCLEIC ACID AND PROTEIN SYNTHESIS

• Take note at Carbon #6: Guanine has carbonyl group;


while Adenine has amino group.
• Pneumonic: Silver (Ag)
FOR PYRAMIDE BASES
• “-idine”
• cytidine, uridine, thymidine
NUCLEOSIDE FORMATION
• Monosaccharide + nitrogen-base
FOR PURINE BASES
• A nucleoside is formed by joining a carbon of the
• “-osine”
monosaccharide with a N atom of the base.
• adenosine, guanosine
• Bonded by beta-N-glycosidic linkage
NAME THE FOLLOWING NUCLEOSIDES:

1. Cytidine

2. Deoxycytidine

TO NAME A NUCLEOSIDE

1. Pyrimidine base = use the suffix -idine


3. Deoxyadenosine
2. Purine base = use the suffix -osine
3. For deoxyribonucleosides, add the prefix deoxy-
4. For ribonucleosides, no need for prefix.

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MODULE 5: NUCLEIC ACID AND PROTEIN SYNTHESIS

NUCLEOTIDE 3. Deoxyadenosine 5’-monophosphate (dAMP)


• Building blocks of nucleic acids
• Nucleoside with the addition of phosphate group
• Three components: SUGAR, NITROGEN-BASES,
PHOSPHATE GROUP

4. Adenosine 5’-diphosphate (ADP)

PHOSPHATE GROUP
• Third component
• Derived from phosphoric acid (H3PO4)

5. Adenosine 5’-triphosphate (ATP)

NUCLEOTIDE FORMATION
• Phosphate group is attached on the 5th Carbon of
Monosaccharide.
• Nucleotides are formed by adding a phosphate group to
the 5′-OH of a nucleoside.
• Nucleotides are named by adding term:
o 5’-monophosphate
• Pentose sugar + nitrogen-containing base = Nucleoside DNA NUCLEOTIDES
• Nucleoside + Phosphate = Nucleotide

BASE ABBR NUCLEOSI DE NUCLEOTI DE

Deoxyadenosine
ADENINE A Deoxyadenosine 5’-monophosphate
(dAMP)
Deoxyguanosine
GUANINE G Deoxyguanosine 5’-monophosphate
(dGMP)
Deoxycytidine
CYTOSINE C Deoxycytidine 5’-monophosphate
(dCMP)
Deoxythymidine
NAME THE FOLLOWING NUCLEOTIDES THYMINE T Deoxythymidine 5’-monophosphate
(dTMP)
1. Cytidine 5’-monophosphate (CMP)
DNA NUCLEOTIDES

BASE ABBR. NUCLEOSI DE NUCLEOTI DE

Adenosine
ADENINE A Adenosine 5’-monophosphate
(AMP)
Cytidine
2. Deoxycytidine 5’-monophosphate (dCMP)
GUANINE G Guanosine 5’-monophosphate
(GMP)
Cytidine
CYTOSINE C Cytidine 5’-monophosphate
(CMP)
Uridine
URACIL U Uridine 5’-monophosphate
(UMP)

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MODULE 5: NUCLEIC ACID AND PROTEIN SYNTHESIS

SUMMARY OF NUCLEIC ACID COMPONENTS


• A polynucleotide contains a backbone consisting of
alternating sugar and phosphate groups.
• A polynucleotide has one free phosphate group at the
5’ end and one free OH group at the 3’ end.
• In DNA, the sequence of the bases carries the genetic
information of the organism.

IMPORTANT POINTS!
• Each nonterminal phosphate group of the sugar-
phosphate backbone is bonded to two sugar molecules
NUCLEIC ACID FORMATION through 3’-5’-phosphpdiester linkage.
• A nucleotide chain has directionality.
NUCLEIC ACIDS • The two strands of DNA are ant-parallel.
• Nucleic acids are polymers of nucleotides joined by
phosphodiester linkages. NUCLEIC ACID BACKBONE
• Alternating sugar-phosphate chain in a nucleic acid
structure. (constant)
o DNA = Alternating phosphate and deoxyribose sugar
units
o RNA = Alternating phosphate and ribose sugar
• Specific Bases
o DNA = Thymine
o RNA = Uracil

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MODULE 5: NUCLEIC ACID AND PROTEIN SYNTHESIS

• Involves 2 polynucleotide strands coiled around each


other in a manner somewhat like a spiral staircase.
• The two strands run in a opposite direction.
• The two strands are antiparallel.
• The two strands are connected by hydrogen bonds
between their bases.

• There are complementary base pairs that always


NITROGENOUS BASES IN NUCLEIC ACIDS hydrogen bond together in a particular manner.

BASE DNA RNA


ADENINE Yes Yes
GUANINE Yes Yes
CYTOSINE Yes Yes
THYMINE Yes

URACIL Yes

• CHARGAFF’S RULE
o It states that the amount of Thymine will always be
equal to the amount of Adenine; the amount of
Cytosine will always be equal to the amount of
Guanine.
o And these bases are held by hydrogen bonds
o Purine = Pyrimidine
o A=T;C=G
▪ Thymine- Adenine base pairing = 2 hydrogen
bonds
▪ Cytosine- Guanin base pairing = 3 hydrogen
VARIABLE PORTION/CHANGING PORTION bonds
o Sequence of bases attached to the sugar unit of the
backbone. This sequence is the distinguishing factor CHROMOSOMES
of various DNA and RNA from each other • A threadlike structure of nucleic acids and protein found
in the nucleus of most living cells, carrying genetic
information in the form of genes.
• Humans have 46 chromosomes (23 pairs).
• A gene is the portion of the DNA molecule responsible for
the synthesis of a single protein.

THE STRUCTURE OF CHROMOSOMES

DNA helices that wind


HISTONES around a core of protein
molecules
NUCLEOSOMES Group of histones in chain
CHROMATIN Chain of nucleosomes
a sequence of nucleotides
in DNA or RNA that
GENE
THE DNA DOUBLE HELIX encodes the synthesis of
• Model was proposed initially by James Watson and specific proteins
Francis Crick in 1953.
• DNA consists of two polynucleotide strands that wind
into a right-handed double helix.

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MODULE 5: NUCLEIC ACID AND PROTEIN SYNTHESIS

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Module 5:
NUCLEIC ACIDS AND PROTEIN MTChem2:Biochemistry for MLS
(Lecture)
SYNTHESIS
College A.Y. 2021 – 2022 – 2

OUTLINE
I. Central Dogma of Molecular Biology
A. Replication
B. Transcription
C. Translation (Protein Synthesis)
II. DNA vs RNA
III. Mutations
A. Types of Mutations
B. Examples

CENTRAL DOGMA OF MOLECULAR BIOLOGY


 When we say central dogma of the molecular biology
these are the primary stats that are needed for you to be
able to form a protein in our body.
 Central Dogma is usually composed of 2 main steps
(Transcription and Translation). However, for the sake of
the discussion we will include replication as part of
Central Dogma. Replication is a pre-step before entering
the central dogma. (Some sources don’t include
replication while others include it)

 Replication
o the process by which DNA makes a copy of itself
when a cell divide.
o That’s why the symbol for replication is “Pabaliktad
na arrow” that means DNA to DNA DNA REPLICATION
o Nucleus- the process of replication and transcription  First step of Central dogma
 the process by which DNA makes a copy of itself when a
 Transcription cell divide
o ordered synthesis of RNA from DNA o DNA to DNA
o The arrow points from DNA and it becomes RNA  biochemical process by which DNA molecules produce
specifically mRNA DNA  RNA (mRNA) the exact duplicates of themselves.
o genetic information stored in DNA is passed onto o So when we say they have exact duplicates of
RNA. themselves, they can duplicate themselves exactly
o Happens in nucleus because of parent DNA
o Parent DNA also known as Template or Pattern
 Translation DNA, Original DNA or Parent Strand/DNA.
o synthesis of proteins from RNA; o It can duplicate themselves because it undergoes
o genetic information determined the specific amino SEMICONSERVATIVE REPLICATION.
acid sequence of the protein.  The original (parent DNA) DNA molecule forms two
o The arrow which is represented in translation is RNA new DNA molecules, wherein each of your DNA molecules
 Protein. Usually in other books: RNA  Amino have 1 strand from the parent DNA.
Acid (Basic unit of proteins)  Based from your diagram, the parent DNA is
o Occurs in cytoplasm (specifically in Ribosomes) represented as blue strand, DNA is a double helix structure
so meaning you have 2 strands. Now your parent DNA will
be divided into 2 Once these two strands are divided to
each other, it is so called as Template DNA, because this
will be the template or pattern of formation of exact
duplicates called daughter DNA. From template DNA it will
now copy its partner or their complement forming 1
daughter DNA and another daughter DNA. When you
compare these 3, they will all look the same because they
came from 1 parent DNA.
o . (1 strand from Parent DNA will go to the 1 strand of
daughter DNA, while the other Strand of Parent DNA
will go to the 2nd Daughter DNA).
o Once you are able to form your 2 daughter DNA, it
will now compose of
 -one strand of parent DNA,
 ONE NEWLY FORMED STRAND
 The end result of replication process is 2 Daughter DNA.\
o Parent DNA  2 Daughter DNA

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MODULE 5: NUCLEIC ACIDS AND PROTEIN SYNTHESIS

 Once you already separate your parent DNA, 1 strand is


for 1 daughter DNA. While the other Parent strand will be
for 2nd Daughter DNA. Both of which will form a new
reformed strand. Same pattern given by the Parent DNA.
Noticed that the new formed strands are different. 1st
daughter DNA on top forms a strand that grows
CONTINOUSLY (Mahaba formation niya) while the
other Daughter DNA if you would notice, its formation of
new strand is in segments (short fragments)

COMPLEMENTARY BASES IN DNA TO DNA:


 Once your parent DNA are separated from each other,
you are able to form new strand which are
o Lagging strand –grows in short segment also known
as “Okazaki fragments”
 Okazaki Reiji (The one who discovered it)
FIRST STEP IN REPLICATION IS THE UNWINDING o Leading strand - Grows continuously (no Nicks)
OF THE DNA HELIX o NICKS– spaces, breaks or gaps in the fragments
 You are able to form Lagging strand and Leading
 First step in Replication is the unwinding of the DNA helix strand because of enzyme, DNA Polymerase.
(parent DNA).
o Separation of 2 DNA strands.  DNA Polymerase
o For you to be able to unwind the DNA double helix o Checks or verifies the base pairing is correct
we have your enzyme:  Means that your parent DNA and your leading strand
 DNA Helicase is correct.
- enzyme that causes the DNA helix to unwind (red o Catalyzes the formation of a new phosphodiester
color). linkage between nucleotide and growing strand.
- serves as the zipper of our DNA Helix. o Functions both in two Daughter DNA
- DNA Helicase should be used when answering o Works in opposite direction (One DNA polymerase
question about what causes DNA Helix to unwind. moves from left, one moves from right). This is due
- (-ase) = enzyme to DNA which works in anti-parallel direction
- DNA helicase works in a specific point which is o (Opposite complementary strands).
Replication fork  Forms only DNA Daughter strand in 5’ to 3’
direction

 Replication Fork
o Point at which unwinding occurs; constantly
changing or moving.
o As the DNA Helicase move, the replication fork
occurs.

 Second step, separate and form a new strand. Whenever


you form two strand this is how it looks like.

 DNA Ligase
o Connects the okazaki fragments together to
synthesize a newly formed strand (continuous).
o Forms phosphodiester bonds in between strand

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MODULE 5: NUCLEIC ACIDS AND PROTEIN SYNTHESIS

o Daughter DNA should not have nicks. For you to be


able to remove this nick, we have DNA Ligase (helps TYPES OF RNA MOLECULES
connecting several unit).
TYPE ABBREV DEFINITION

Heterogeneous  Aka ptRNA or primary


RNA hnRNA transcript RNA (Primary
strand forms after DNA
transcription)
 Formed directly by DNA
transcription
Messenger  carries the information
RNA mRNA from DNA to the ribosome
 Product after transcription
RECAP  Blueprint of protein
 DNA Helicase unwinds the Parent DNA strand. The point assembly
where the helicase works upon is Replication fork
 Once your parent DNA is separated already, it forms a Small nuclear  Facilitates the conversion
complementary strand using DNA Polymerase. Once RNA snRNA of hnRNA to mRNA
your DNA Polymerase acts upon the two-parent strand,  Contains 100 to 200
you are able to form your leading strand which forms nucleotides
continuously and lagging strand which forms in segment.
 Third step is the action of DNA Ligase wherein it forms Ribosomal  provides the site where
your phosphodiester bond between Okazaki fragments to RNA rRNA polypeptides are
complete the daughter DNA below. assembled during protein
 End result of replication: 2 Daughter DNA synthesis
o Complementary Base Pair  Assembly location for
 A= T transcription
 C=G  Do not contain
informational function.
 Works with several protein
so it can be a location site
Transfer RNA  brings specific amino
tRNA acids to the ribosomes for
protein synthesis
 Smallest type since it has
75-90 nucleotide units.

KEYPOINTS IN DNA REPLICATION:

1. Replication occurs inside the nucleus.


 Our DNA can be found in NUCLEUS, especially
chromosome. DNA is inside the chromosome

2. It occurs at any location within the molecule.


 Chromosome is composed of long chain of DNA.

3. DNA replication is bidirectional.


 Because of anti-parallel of DNA double Helix strand

4. Chromosomes – individual DNA molecule


bound to a group of proteins  DNA Replication for first step and the hnRNA is your
primary transcript for your DNA Transcription.
DIFFERENCE BETWEEN DNA AND RNA  snRNA helps in the conversion of hnRNA to mRNA.
 mRNA is our blueprint in protein assembly because it will
DNA RNA be used in the last step of Central Dogma which is
Translation. It is also used for you to have protein. If you
LOCATION Within the nucleus In all parts of a cell don’t have your mRNA therefore you will not have protein.
(pakalat kalat)  rRNA is found between your mRNA and tRNA since it is
Double stranded (2 Single Strand the site for translation process.
STRUCTURE strand)  tRNA is your bringer to convert the information in mRNA
Sugar: Deoxyribose Sugar: Ribose for protein.
(Doesn’t have OH in A=U; G=C
Carbon-2) TRANSCRIPTION
A=T; G=C
FUNCTION Storage and transfer Synthesis of  the ordered synthesis of RNA from DNA; the genetic
of genetic proteins information stored in DNA is passed onto RNA.
information

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MODULE 5: NUCLEIC ACIDS AND PROTEIN SYNTHESIS

o DNA helix would be separated or unwind, once the


DNA unwinds, you are now able to form 3 mRNA
through the help of RNA Polymerase.
 the process by which DNA directs the synthesis of
hnRNA/mRNA molecules that carry the coded
INTRONS
information needed for protein synthesis.
o DNA  RNA (mRNA) o Gene segment that does not code for genetic
o End Result in transcription: formation of mRNA information
o are DNA segments that interrupt a genetic
CHROMOSOME message.
o Represented by Blue code; does not have genetic
o DNA is found in chromosome information
o Organized package of DNA located in the nucleus o Splicing – cut introns
 Nucleosome- group of histones (after unwinding
chromosome this is the result)
 Centromere- center part of chromosome
 P arm- upper part of chromosome EXONS
 Q arm- lower part of chromosome o Gene segment that codes for genetic information.
 Histones- tiny coiled DNA structures/ strands o are DNA segments that help express a genetic
o Humans – 23 pairs of chromosomes (46) message
 22 pairs = Autosomes or Somatic (Homologous) o Represented by red code; have genetic information.
 1 pair = sex chromosomes (identifies whether they
are male XY or female XX)

SPLICING
o process of removing introns from an hnRNA
molecule and joining the remaining exons together to
form an mRNA molecule.
o Splicing occurs when there is a short segment of
gene. DNA was converted into hnRNA.hnRNA is
produced by various segment. These segments are
called Introns and Exons.
o snRNA are located in spliceosomes

GENE
o Segment of a DNA strand that contains the base
sequence for the production of a specific mRNA
molecule
o 1 Gene = 1000 to 3500 nucleotides  The splicing process involves snRNA molecules. An
snRNA molecule is always found complexed with proteins
in particles called small nuclear ribonucleoprotein
particles, which are usually called snRNPs (pronounced
“snurps”).
 A small nuclear ribonucleoprotein particle is a complex
formed from an snRNA molecule and several proteins.
“Snurps” always further collect together into larger
complexes called spliceosomes. A spliceosome is a
large assembly of snRNA molecules and proteins
involved in the conversion of hnRNA molecules to mRNA
molecules.

TRANSCRIPTION PROCESS TEMPLATE STRAND


 Conversion of DNA to mRNA, in between these two, DNA  used to synthesize RNA
will be converted first into hnRNA o Used to convert for RNA
 hnRNA will be further edited until such time it will become  Blue strand
mRNA.  runs 3’ to 5’ direction
 hnRNA can be edited into mRNA through splicing. o Converts into RNA

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MODULE 5: NUCLEIC ACIDS AND PROTEIN SYNTHESIS

Template strand (DNA):


INFORMATIONAL STRAND (NON-TEMPLATE
STRAND)
 not involved in RNA synthesis mRNA strand:5’ – G A U C G U A U C C A A -3’
 “Non-Template Strand”
 Red strand Informational Strand and m RNA have same direction, but
different in base pairs (A-U).
RNA POLYMERASE
 governs the unwinding process in transcription TRANSLATION
 the enzyme that synthesizes RNA from a DNA template  process of transferring genetic information from RNA to a
in the transcription process. sequence of amino acids in a protein
 occurs in ribosomes

 Codon
o Is three-nucleotide sequence in an mRNA molecule
that codes for a specific amino acid
o 3 nucleotides = 1 codon = 1 amino acid

 Anti-codon
o complementary or opposite of codon; present in
tRNA

TRNA
 delivers amino acids to the mRNA

 Each of the different tRNA molecules is specifically


recognized by an aminoacyl tRNA synthetase enzyme.

 tRNA is drawn as a cloverleaf shape, with an acceptor


stem at the 3’ end, which carries the needed amino acid,
and an anticodon, which identifies the needed amino
acid.

MAIN STEPS IN TRANSCRIPTION:

1. A portion of the DNA double helix unwinds by the help of


RNA polymerase. One strand becomes the template strand
which will be used to synthesize the RNA.

2. Template strand is copied proceeding in the 3’ to 5’


direction. mRNA formed runs in the opposite direction: 5’ to
3’ direction.

3. Base pairing now starts and when converting DNA to=


RNA, A is now partnered with U while G is still partnered with
C.

4. Transcription ends when the RNA polymerase enzyme


encounters a sequence of bases that is “read” as a stop
signal.

TRANSCRIPTION- SAMPLE STRAND CONVERSION


1

Informational strand: 5’ – G A T C G T A T C C A A – 3’

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MODULE 5: NUCLEIC ACIDS AND PROTEIN SYNTHESIS

 rRna
 Links between amino acids are peptide bonds, and
polypeptides for more amino acid.
PROTEIN SYNTHESIS ELONGATION
 The genetic code is the assignment of the 64 mRNA
codons to specific amino acids (or stop signals).
 Elongation proceeds as the next tRNA molecule delivers
 Marshall Nirenberg and Har Gobind Khorana (Nobel
the next amino acid, and a peptide bond forms between
Prize)
the two amino acids.
 Initiation codon: AUG
 The genetic code is highly degenerate; many amino acids
are designated by more than one codon.
o Example
 ACU  Thr or Threonine
 GGU  Gly OR Glycine
 UAA  Stop
mRNA tRNA AA
Codon Anticodon
AAA UUU Lys
CGC GCG Arg
AGA UCU Arg
UAG AUC Stop
TERMINATION

 Translation continues until a stop codon is reached, which


is called termination; the completed protein or polypeptide
formed is released.
 End result: Protein or Polypeptides

 STOP CODONS:
o UAG
o UGA
o UAA

STRAND CONVERSION-2
STAGES OF TRANSLATION
DNA Template strand:
3’– A G C T G G C A A T T G A T A –5’
INITATION
mRNA: 5’ – U C G A C C G U U A A C U A U – 3’
 Initiation begins with mRNA binding to the ribosome.
Codon: UCG – ACC –GUU –AAC –UAU
 tRNA brings the first amino acid, always at codon AUG.
o AUG = START codon
tRNA anticodons: AGC – UGG – CAA – UUG - AUA
o AUG = codes for Methionine

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MODULE 5: NUCLEIC ACIDS AND PROTEIN SYNTHESIS

Polypeptide: Ser – Thr – Val – Asn – Tyr

DELETION MUTATION

 occurs when one or more nucleotides is/are lost from a


STRAND CONVERSION-3
DNA molecule.
- ANSWER THIS -

DNA Template strand:


3’– T A G C T T A A A A G C G A A –5’

mRNA

tRNA anticodons INSERTION MUTATION


 occurs when one or more nucleotides is/are added to a
Polypeptide DNA molecule.

STRAND CONVERSION-4

DNA Informational strand:


5’– A T G G G C C G C T A G T A T –3’

DNA Template strand: 3’ – T A C C C G G C G A T C A T


A – 5’
SILENT MUTATION
Mrna: 5’ A U G G G C C G C U A G U A U – 3’  has a negligible effect to the organism, because the
resulting amino acid is identical.
Codon: AUG – GGC – CGC – UAG – UAU

tRNA anticodons: UAC – CCG – GCG AUC AUA

Polypeptide: Met Gly Arg Stop

OTHER INFORMATION
 A mutation that produces a protein with one different
amino acid usually has a small to moderate effect on the
protein overall.
 For some proteins, such as hemoglobin, substitution of
just one amino acid can result in the fatal disease sickle
cell anemia.

 Replication – Nucleus , end result: 2 daughter dna


 Transcription – Nucleus, end result: mRNA  If a mutation causes a big change, like producing a stop
 Translation – Ribosomes, end result: Proteins codon, the remainder of the protein will not be
synthesized, which can have catastrophic results.
MUTATIONS AND GENETIC DISEASES

 A mutation is a change in the nucleotide sequence in a


molecule of DNA.
 Some mutations are random, others are caused by
mutagens, chemicals that alter the structure of DNA.

CLASS MUTATION ACCORDING TO CHANGE

POINT MUTATION

 is the substitution of one nucleotide for another

BONIFACIO, ROSELEEN FEI B. BSMT-1E , BERNARDO, VANESSA G. BSMT1-F 7


MODULE 5: NUCLEIC ACIDS AND PROTEIN SYNTHESIS

BONIFACIO, ROSELEEN FEI B. BSMT-1E , BERNARDO, VANESSA G. BSMT1-F 8


Module 6: MTChem2:Biochemistry for MLS
Introduction to Metabolism, Citric Acid (Lecture)
Cycle, & Electron Transport Chain College A.Y. 2021 – 2022 – 2

• As illustrated, larger molecules into smaller ones with the


OUTLINE release of energy is: catabolism. A smaller molecule plus
I PART 1 energy which is absorbed is: anabolism.
A Introduction
B Categories of Metabolism METABOLIC PATHWAYS
C Cell Structure (Mitochondria)
D Stages of Metabolism • The metabolic reactions that occur in a cell are usually
II Part 2 organized into sequences.
A Coenzymes • Metabolic pathways are a series of consecutive
B Adenosine Phosphates biochemical reactions used to convert a starting material
C Nicotinamide Adenine Dinucleotide into an end product.
D Flavin Adenine Dinucleotide
E Coenzyme A

PART 1: METABOLISM
• Metabolism is the sum of all the chemical reactions that
take place in an organism.
• There are a lot of people who mistakenly mismatch the
metabolism and digestion because these two terms are
very different from one another. TWO TYPES OF METABOLIC PATHWAYS

METABOLISM VS. DIGESTION LINEAR PATHWAY


METABOLISM • Is a series of reactions that generates a final product
• Refers to how the cells utilize the energy we have different from any of the reactants.
absorbed from food during digestion. It is also called as • Linear, on the word itself, is a straight chain of reaction;
an “intracellular process” since the process is being from the first reactant to a final product in a way that these
done inside the cells. two are different.

DIGESTION
• Refers to how the body processes food in the
gastrointestinal (GI) tract and eliminates food waste via
the intestines. It is also called as an “extracellular CYCLIC PATHWAY
process” wherein it doesn’t involve the cells.
• Is a series of reactions that regenerates the first reactant.
For the stages of metabolism, take note that digestion is on • The first reactant is the same with the final product.
the stage 1; although it is a stage of metabolism, this is not • This pathway is in a circular motion so it is a never-
considered as metabolism since it should require the ending process where the reactant is also being
utilization of cells. generated into the final product and vice versa.
• A good example of cyclic pathway is the Krebs cycle or
CATEGORIES OF METABOLISM the Citric acid cycle.
CATABOLISM
• Is the breakdown of large molecules into smaller ones.
Energy is generally released during catabolism.
• Example: Hydrolysis of starch
– Starch is a polysaccharide carbohydrate that contains
multiple sugar units, specifically, glucose.
– Hydrolysis, in general, is catabolic in nature (from the
starch and at the addition of water, we catabolize this PROKARYOTIC VS. EUKARYOTIC
large molecule into a smaller glucose units).

ANABOLISM
• Is the synthesis/creation of large molecules from
smaller ones. Energy is generally absorbed during
anabolism.
• In this type of process, we are not destroying anything but
rather, creating a bigger molecule.
• Example: Synthesis of protein from component amino
acids – amino acids are the smaller parts of protein
degradation.

EUKARYOTIC CELL
• Is a cell in which the DNA is found in a membrane-
enclosed nucleus.
• Cytoplasm is the water-based material of a eukaryotic
cell that lies between the nucleus and the outer
membrane pf the cell.
o Cytosol is the water-based fluid part of the
cytoplasm of a cell.

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MODULE 6: INTRODUCTION TO METABOLISM

THREE (3) IMPORTANT ORGANELLES: steps in the biochemical energy production process and
1. Ribosomes – site of protein synthesis numerous reactions are associated with each phase.
2. Lysosomes – contains hydrolytic enzymes needed for
cellular rebuilding, repair, and degradation. FOUR STAGES OD METABOLISM
3. Mitochondria – responsible for the generation of most of
the energy for a cell. STAGE 1: DIGESTION (EXTRACELLULAR)
• Is a stage in metabolism but IS NOT considered a
metabolism since it is outside the cell. This is an
extracellular process where the food is being digested
or broken down into pieces.
• Catabolic in nature which means it converts large
molecules to a small ones.
• The catabolism of food begins with digestion, which is
catalyzed enzymes in the saliva, stomach, and small
intestines.
• Digestion converts large molecules into smaller
components.

MITOCHONDRIA/MITOCHONDRION
• A small sausage-shaped organelle in which energy
production takes place, hence they are called the
“powerhouse of the cell” (outer membrane & inner
multi-folded membrane).
• Outer membrane (50% lipid, 50% protein) is freely
permeable to small molecules
o When we say permeable, this means that it can
allow small substances to pass through.
• Inner membrane (20% lipid, 80% protein) is highly
impermeable to most substances.
o When we say impermeable, this means that it
cannot allow most of the substances to enter its • The most common end product of digestion are the
region.
following:
• In order for the mitochondria absorb molecules, they 1. Fatty acid which came from triacylglycerols that
should be broken down first into smaller ones. is present in fatty rich foods.
• The nonpermeable nature of the inner membrane divides 2. Monosaccharides which came from our
a mitochondrion into two separate compartments: carbohydrates that is present in starch, pasta,
o Matrix – the interior region; this is where the rice, etc.
energy production occurs 3. Amino acids which came from proteins, a larger
– this is the most important part in mitochondria version of our amino acid that is present in meat.
since the matrix holds the ATP synthase • The three end products mentioned also have their own
complex that is needed in our metabolism. metabolism:
o Intermembrane Space – the region between o For fatty acid, we have the fatty acid oxidation
inner and outer membranes o For monosaccharide, we have glycolysis
• Cristae is the folds of the inner membrane that protrude o For amino acids, we have amino acid
into the matrix. oxidation
• ATP synthase complexes is a small spherical knobs • These end products will now be transported in our small
attached to the cristae. As their name implies, these intestines where they will be reabsorbed in our
relatively small knobs, which are located on the matrix bloodstream so that they can be transferred into our cells.
side of the inner membrane, are responsible for ATP
synthesis.

• As illustrated, the hydrolysis of carbohydrates to


monosaccharides begin with amylase enzymes in the
saliva and continues into the small intestine.
• The enzyme present in our saliva is what we call
amylase.
• Remember, in order for us to hydrolyze our starch, we
need to add amylase which is an enzyme that breaks
down the glycosidic bonds that connects our starch.
Once we destroy these bonds, we can extract simple
monosaccharide units such as glucose. These small
The energy needed to run the human body is obtained from monosaccharide units will be reabsorbed in our small
ingested food through a multi-step process that involves intestines and will be transported via bloodstream into our
several different catabolic pathways. There are four general cells.

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MODULE 6: INTRODUCTION TO METABOLISM

of acetyl CoA is oxidized to carbon dioxide and the


reduced coenzymes FADH2 and NADH are produced.
• Once the biomolecules on this stage enter the cell, they
will be further degraded into acetyl groups and these
acetyl groups will combine with our coenzyme A to
produce acetyl CoA which will deliver these acetyl
groups through our Krebs cycle. Acetyl CoA will then
serve as “transferring vessel” to our next stage
• Next would be in our protein digestion that begins in our (Krebs Cycle)
stomach where acid (usually HCl) denatures the protein • In Krebs cycle, the acetyl CoA will be oxidized further to
and the protein pepsin begins to cleave the protein produce carbon dioxide and energy which is basically
backbone into smaller peptides and amino acid. the primary goal of this stage.
• For our stomach, the enzyme present is pepsin that • These coenzymes (coenzyme A, FADH2, and NADH)
breaks down the protein molecule intro our polypeptides serve as our carriers of energy.
and amino acids. • Again, the leftover energy in this stage will be delivered
• Digestion of these protein molecules will continue in the by FADH and NADH to the stage 4 – electron transport
small intestines where trypsin and chymotrypsin further chain.
cleave the protein backbone to form amino acids. • The CO2 that is exhaled as part of the breathing process
comes primarily from this stage.

• Lastly, the triacyglycerols, the most common lipids are


oxidation
• first emulsified by our biles – a liquid part which are
secreted by our liver that emulsifies (mix) and
dehydrolyze the triacylglycerols and fatty acid by the
enzyme lipase in the small intestines.
STAGE 4: ELECTRON TRANSPORT CHAIN AND
STAGE 2: FORMATION OF ACETYL COA OXIDATIVE PHOSPHORYLATION
(INTRACELLULAR) (INTRACELLULAR)
• Once our biomolecules are cleaved/digested, they will be • Also occurs inside the mitochondria.
reabsorbed in our small intestine and will travel through • Electron transport chain is a series of biochemical
the bloodstream and be delivered into our cells.
reactions in which electrons and hydrogen ions from
• Regardless of what type of biomolecules they are, they NADH and FADH2 are passed to intermediate carriers
will all be degraded into acetyl groups – that starts our and then ultimately react with molecular oxygen to
second stage or the formation of acetyl CoA. produce water. NADH and FADH2 are oxidized in this
process.
• Oxidative phosphorylation is the biochemical process
by which ATP is synthesized from ADP as a result of
the transfer of electrons and hydrogen ions from NADH
or FADH2 to 02 through the electron carriers involved in
the electron transport chain.

• Stage 2 involves numerous reactions (some of which


occur in the cytosol of cells and some in cellular
mitochondria).
• Monosaccharides, amino acids, and fatty acids are
degraded into acetyl groups (CH3CO-), two carbon units
is now bonded to coenzyme A which is a coenzyme that
aids in the process of energy production. Once these two
carbon units from acetyl groups are bonded to coenzyme
A, they will form acetyl CoA.
• Acetyl CoA is a molecule that participates in many
biochemical reactions in proteins, carbohydrates, and
lipid metabolism. Its main function is to deliver the acetyl
group to the citric acid cycle/krebs cycle to be oxidized for
energy production.
• Pyruvate is a product of glycolysis.

STAGE 3: CITRIC ACID CYCLE (INTRACELLULAR)


• Citric acid cycle, often called as the Krebs cycle, is a
series of biochemical reactions in which the acetyl portion

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MODULE 6: INTRODUCTION TO METABOLISM

2. Adenosine diphosphate (ADP) – composed of 2


COENZYMES IN METABOLISM phosphate groups that are attached to ribose-adenine
• Coenzyme is an organic compound needed for an structure.
enzyme-catalyzed reaction to occur. 3. Adenosine triphosphate (ATP) – composed of 3
• These small molecules cannot catalyze a reaction by phosphate groups that are attached to ribose-adenine
themselves but they can help other enzymes and structure.
molecules to do so.

FUNCTIONS & IMPORTANCE OF COENZYMES IN


HUMAN BODY
• Supply energy (ATP, ADP) – the hydrolysis of these
coenzymes provides the energy needed for many
essential processes in organisms and cells.
o Remember that in catabolism, when large *Illustrated below is the closer look to the chemical structure
molecules are degraded into smaller ones, they of Adenosine Phosphates.
release energy in the process and this energy in
turn, is used to activate important processes.
o One of the sources of energy is the hydrolysis or
catabolic reaction of our ATP and ADP.
• Participates in redox reactions (NAD+, NADH, FAD,
FADH) - nicotinamide adenine dinucleotide & flavin
adenine dinucleotide
o Redox reaction is a reaction that involves the
transfer of electrons between two species.
o Notice that we have NADH and FADH: these
are the reduced forms of the oxidized forms of
our coenzymes.
• Activation of acetyl groups (Coenzyme A) – small
biomolecules from our food are further degraded into
acetyl groups and react to coenzyme A to produce acetyl • On the right side, we have the purine (adenine) which is
CoA which in turn, transfer these acetyl CoA groups to commonly found on DNA. We also have ribose which is
next stage of biochemical energy production which is the a simple sugar and lastly, we have phosphate ions,
Krebs Cycle. which are attached to the fifth carbon atom of our ribose
structure.
LAW OF REDOX REACTIONS • Depending on the number of phosphate confirms the
LEORA VS. GEROA identity of our adenosine phosphate.
• LEORA – Loss Electron Oxidation Reducing Agent • Again, adenosine is the bonded form of our adenine and
• GEROA – Gain Electron Reduction Oxidizing Agent ribose. So adenine + ribose, when bonded together, is
called adenosine 5’-triphosphate.

What are the bonds that are present on your adenosine


phosphate structures?

1. Phosphoester bond (phosphate-ribose bond)


2. Phosphoanhydride bond (phosphate-phosphate
• A good example in applying our redox reaction is the bond) is the chemical bond formed when two
conversion of FAD to FADH. Naturally, FAD is our phosphate groups react with each other and a water
oxidizing agent while FADH is our reducing agent. molecule is produced.
• So if we want to reduce our FAD, following the reduction
process, we can add extra hydrogen atoms to the
structure of FAD, which in turn, creates our FADH.
• Most commonly on our coenzymes, the one with the extra
hydrogen atom is the one that is reduced.

FOUR (4) NUCLEOTIDE-CONTAINING


COMPOUNDS

• Adenosine Phosphates (ATP, ADP, and AMP)


• Nicotinamide Adenine Dinucleotide (NAD+, NADH)
• Flavin Adenine Dinucleotide (FAD, FADH2)
• Coenzyme A (CoA-SH)

ADENOSINE PHOSPHATES (ATP, ADP, AND AMP)


• Several adenosine phosphates exist in nature but we’ll
just have to focus on these three namely:

1. Adenosine monophosphate (AMP) present in RNA


molecules – the most simple among the three since
it contains only one phosphate group in their structure.

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MODULE 6: INTRODUCTION TO METABOLISM

PHOSPHORYL AND PHOSPHATE GROUP • As illustrated below, there is a reactant with the addition
of water (the molecules of water will attach to the reactant,
1. Phosphoryl group (P)/ PO32- derived from phosphate separating them in the process).
ion when it becomes part of another molecule.

Since we already know the principle of hydrolysis, let us know


• A good example of PO3 2- is the phosphoryl group on the apply this to our adenosine phosphates.
first structure. As we can see, we have single phosphate
ion that is attached to another molecule. • In metabolic pathways, the interconversion of our
• Looking at the chemical structure, we have three oxygen adenosine phosphates such as ATP and ADP is the most
atoms, one single phosphate molecule with 2 important process for the storage and release of energy
negatively charged oxygen atoms. Hence, the name (any process such as walking, running, or even the basic
PO32- is made - these phosphoryl group derived from the ones such as swallowing or breathing is fueled by the
attachment of a single phosphate ion to several release of energy from the hydrolysis of ATP to ADP and
phosphate molecules. vice versa.
• Hydrolysis is catabolic in nature where we destroy a
2. Phosphate group (Pi)/ HPO42- derived from phosphoryl large molecule to a smaller one.
group when ATP is hydrolyzed to ADP molecule • Hydrolysis of ATP cleaves one phosphate group,
forming ADP and hydrogen phosphate, HPO42- . This
reaction releases 7.3 kcal/mol of energy.

• Note: one of the product of hydrolysis is a single molecule


of phosphate ion.
• As we can see on the illustration, we call this a
phosphate group since we already have now a four • Upon the addition of water as a reactant, the water will
oxygen atoms present on the structure – two of them are cleave one phosphate group from our ATP. The end
negatively charged with the addition of hydrogen atoms product would be the ADP with hydrogen phosphate
and one phosphate molecule and the release of energy exactly at 7.3 kcal/mol of
energy.
• As we can see, one molecule of oxygen from water is
ADENOSINE TRIPHOSPHATE (ATP) attached to phosphate group; one molecule of hydrogen
→ adenosine 5'-triphosphate is also attached to phosphate group; and the one
→ is a nucleoside triphosphate formed by adding three hydrogen atom is released in the process (there is also a
phosphates to the 5'-OH group of adenosine, a hydrogen liberated from the process).
nucleoside composed of the sugar ribose and the • The process of hydrolysis can also be applied to ADP. So
base adenine once we cleave the ADP, it will become the adenosine
→ is the most prominent member of a group of "high- monophosphate and will liberate a one hydrogen atom
energy" molecules, reactive molecules that release and a phosphate group.
energy by cleaving a bond during hydrolysis.
ATP SYNTHESIS (PHOSPHORYLATION)
ADENOSINE DIPHOSPHATE (ADP) • The counterpart of hydrolysis
→ adenosine 5'-diphosphate • Adds a phosphate group to ADP, forming ATP.
Phosphorylation requires 7.7 kcal/mol of energy.
ADENOSINE MONOPHOSPHATE (AMP) • Unlike hydrolysis wherein there is catabolic or the
destruction of a large molecule into smaller ones, in ATP
→ adenosine 5'-monophosphate
synthesis, there is anabolic process – we are creating
larger molecule using smaller substances.
DIFFERENT ROLES OF ADENOSINE PHOSPHATES

ATP/ADP HYDROLYSIS
• Hydrolysis – a chemical reaction in which water is used
to break down bonds of a particular substance.

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MODULE 6: INTRODUCTION TO METABOLISM

• Have a B vitamin as a structural component


(Nicotinamide)
• Both can be represented structurally by using a three-
subunit and six-subunit formulation
• Have an oxidized (NAD+) and a reduced form (NADH)

• In this process, we add a phosphate group instead of


water to a smaller substance such as ADP or AMP
(whichever is available). But, the most common one is our
ADP, forming the ATP. Unlike hydrolysis which releases
energy, there is in energy absorption in ATP synthesis.
With that, an equal amount of 7.3 kcal/mol of energy is
absorbed rather than released.
• The products in the illustration above can also be our • When a coenzyme gains hydrogen atoms – that is, H+
reactants. Just like in the ATP and water, if we will and e- –the coenzyme is reduced; thus, the coenzyme
reverse it, it will be the hydrolysis already. is an oxidizing agent.
• When a coenzyme loses hydrogen atoms – that is, H+
Below is the summary of Hydrolysis and ATP Synthesis: and e- – the coenzyme is oxidized; thus, the coenzyme
is a reducing agent.

ADENOSINE PHOSPHATES (ATP, ADP, AND AMP)


• Aside from our energy production, adenosine phosphates
can aid in other specific metabolic reactions such as
glycolysis. They can also add or bring phosphate group
to glucose units. • On our NADs, we have an adenine, a sugar ribose, and
• Its function is not only limited to our energy production but two phosphate molecule or a phosphoryl group –
• rather, we can also add a phosphate group to other these three molecules/structures makes up out ADP.
molecules. • Attached to our terminal phosphate group on the second
part is an extra ribose sugar and on the extra ribose
sugar, attached the active portion of NAD which is the
nicotinamide vitamin.
• Although the structure of NAD is very complex, it is the
six-membered ring containing positively charged nitrogen
atom which is shown in red on the structure, that
participate in oxidation reaction.
• Among the whole structure of NAD, only the nitrogen
ring participate in oxidation and reduction.
• If we want to reduce our NAD to NADH, we can let our
• The addition of phosphate group to glucose units is the NAD oxidized form to react with our two hydrogen atoms.
first step of glycolysis. • In the illustration, we can see that we have an extra
• A typical cellular reaction in which ATP functions as both hydrogen atom and one liberated hydrogen atom.
a source of a phosphate group and a source of energy is • The more hydrogen a molecule has, the more it is to
the conversion of glucose to glucose-6- phosphate, a reduce.
reaction that is the first step in the process of glycolysis.

There are other nitrogen-containing bases associated FUNCTIONS OF NAD


with nucleotides:
• Only have two products: NAD+ (oxidized form) and NADH
(reduced form).
Uridine triphosphate carbohydrate metabolism
The curved arrow symbolism is often used to depict
(UTP)
reactions with coenzymes.
Guanosine triphosphate protein and carbohydrate
(GTP) metabolism
Cytidine triphosphate lipid metabolism
(CTP)

NICOTINAMIDE ADENINE DINUCLEOTIDE (NAD+,


NADH)
• NAD+ is the oxidized form and the NADH is the reduced
form.
• Have coenzyme functions in metabolic redox pathways • The usage of these molecules or coenzymes connotes
what a product we can have. So when we use our NAD,
that means, our product will be oxidized. When we use

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MODULE 6: INTRODUCTION TO METABOLISM

the reduced form (NADH), that means our product is is aldose. While on D-ribitol, we have an alcohol. That
reduced. means, it contains more hydrogen atoms than of ribose.
• Let’s now apply our NAD to the process of transfer of • On D-ribitol part, connected a nitrogen based ring – flavin.
electrons or hydrogen atoms – a good example is the • If we combine flavin and ribitol together, we’ll have B-
conversion of isocitrate and oxalosuccinate (one of the vitamin which is our riboflavin).
products of Krebs cycle). • Riboflavin – is a vitamin b2 and usually seen or can be
• The reduced form is isocitrate and the oxidized form is acquired through eating vegetables, soybeans, or
the oxalosuccinate. almonds. The importance of this is for our carbohydrate
• The process here is oxidation – there is a removal of breakdown and they can also provide energy.
hydrogen ions.
• The product also became a double bond (from oxygen
atom) instead of single bond.
• If we want to reduce this oxalosuccinate, we can add
NADH and extra hydrogen atom, making it our isocitrate.
• The interconversion of these two helps in the metabolic
pathways or metabolic redox reaction pathway in our
Krebs cycle.

Summary Equation of NAD

• On our FAD structure, the only active part that participate


in our redox reactions is the one that is highlighted in red
FLAVIN ADENINE DINUCLEOTIDE in the illustration.
(FAD, FADH2) • In the illustration, we have two nitrogen atoms and 2
• Is a coenzyme required in numerous metabolic redox carbon atoms so those are the only ones that participate
reactions, on our redox reactions.
• has two forms: • So if we want to reduce FAD, we can add 2 molecules of
o FAD (oxidized form) hydrogen.
o FADH2 (reduced form) contains two more H atoms • If we want to oxidize them in reduced form, FADH2, we
than the oxidized form, which is consistent with the can just remove these hydrogen atoms do that we can go
process of reduction involving hydrogen atom gain back to the original form, the oxidized one.
• This redox reaction regarding the FAD happens also on
Krebs cycle.
Summary Equation of FAD

Dinucleotides are organic molecules which consists of a


phosphate, a pentose, and a nitrogen base. For every COENZYMES USED FOR OXIDATION AND REDUCTION
molecule, they also have two copies.

COENZYME A (COA-SH)
• A derivative of the B5 vitamin pantothenic acid
• In the illustration, we have the adenine, which is a • Not an oxidizing or a reducing agent contains a
nitrogen base and another nitrogen base, which is the sulfhydryl group (SH group), making it a thiol (RSH)
flavin. We also have two copies of phosphate and two • SH group are molecules that contains a sulfur atom with
copies of pentose (ribose). two lone pairs bonded to hydrogen.
• Again, for our AFD, we have ADP which consists of • We can also call our coenzyme as HS-CoA.
adenine, a sugar ribose, and two phosphates.
• Attached to the terminal phosphate of ADP is our ribitol
– this is also our ribose but a reduced one.
• D-ribose which consists of five carbon atoms and D-
ribitol is the reduced one. The difference between these
two is the fact that the primary molecule/group in ribose

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MODULE 6: INTRODUCTION TO METABOLISM

• Coenzyme A is very different from other coenzymes other processes. So if we want to extract energy through
because it does not participate on redox reactions – there our acetyl CoA, we can hydrolyze it to liberate our acetyl
is no oxidized or reduced form. group and coenzyme A.
• Coenzyme is a derivative of our B5 vitamin pantothenic • Remember that the hydrolysis of the usage of water
acid – a soluble vitamin that is required in the creation of molecule act as a breaker or something that breaks the
our coenzyme A. bond in our acetyl CoA.
• Remember that our coenzyme A functions as a carrier of • Our product will be our acetyl group liberating it and
acetyl group. our coenzyme A.
• Upon the hydrolysis reaction, since it’s catabolic in
Chemical Structure of Coenzyme A nature, there is a release of energy, specifically
-7.5kcal/mol. It is negative because the energy is
released – this energy will in turn be used by our body for
other processes.
• Aside from krebs cycle function, it can also be our energy
production.

CLASSIFICATIONS OF METABOLIC INTERMEDIATE


COMPOUNDS

• We have here our phosphorylated ADP, ribose


structure and 2 phosphate group attached to the five
prime carbon of our ribose structure.
• The unique part about the phosphorylated ADP is the
extra phosphate ion on the third carbon of our ribose
structure.
• Remember that phosphoryl group is a phosphate ion
attaching or becoming part of the other molecule, hence,
the name is phosphorylated ADP.
• 2-Aminoethanethiol is the one that houses sulfhydryl
1. The first one is usually done through the interconversion
group or the thiol.
of our adenosine phosphates such as our ATP and ADP.
• SH group is the active part of our coenzyme A – so this o ATP hydrolysis produces ADP molecule and
is the one that participate in the hydrolysis of our co phosphate ion – this is catabolic in nature that is why
enzyme A. there is energy release which in turn, this energy is
used to power up other reactions.
o The counterpart of our ATP hydrolysis is ATP
synthesis or what we call phosphorylation. In this
process, we add a phosphate ion to our adenosine
diphosphate or ADP, creating ATP (anabolic activity)
– there’s an absorption of energy; the energy is
stored.
2. Depending on the number of hydrogen atoms connotes
our identity as our oxidizing or reducing agent – there is
a transfer of electron and hydrogen ions.
3. The transfer of acetyl groups using our coenzyme A is
• Remember that acetyl groups is the degraded part of done on stage 2 of the formation of acetyl CoA.
our biomolecules such as proteins: amino acids, fatty
acids, glycerol, and monosaccharides. These IMPORTANT CARBOXYLATE IONS IN METABOLIC
biomolecules will be further degraded into our cells to PATHWAYS
acetyl groups.
• These acetyl groups will further combine with our acetyl
or our coenzyme A rather forming acetyl CoA. This acetyl
CoA will be then the carrier for our acetyl groups to our
krebs cycle.

• Another function for acetyl CoA is the hydrolysis of the


molecule illustrated above.
• When there is hydrolysis of acetyl CoA, there is the
production of energy so technically, we can also say that
our acetyl CoA can also be a good source of energy for

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MODULE 6: INTRODUCTION TO METABOLISM

• Substrate is the molecule that our enzymes act into.


• In the structure of our carboxylate ions, we have 2 parent
acid: Succinic acid and Glutaric Acid
• The difference between these two is the presence of an
extra carbon atom on our glutaric acid.
• For succinic, there are 4 carbons while for glutaric, there
are 5 carbon atoms.
o Each parent acid have our derivatives – the most
important part here is noting their structures or what
is included on their structures as carboxylate ions.
o For hydroxy derivative, there is a presence of
hydroxy group (-OH): Malic acid and Malate
o Malic acid and Malate are hydroxy derivative of
succinic acid.
o For keto derivative, there is a presence of the ketone
group on the structure of carboxylate ions:
Oxaloacetic acid and Oxaloacetate
o For unsaturated derivative, there is a presence of C
double bond C (C=C): Fumaric acid and Fumarate
• For glutaric, we have:
o Keto derivative: Alpha-ketoglutaric acid and
Alpha-ketoglutarate
o Carboxyhydroxyderivative: Citric acid and Citrate.
The most important part in carbohydroxy derivative
is the presence of both the hydroxyl group and a
carboxylic group.

CASTRO, KATELYN BSMT-1-B 9


Module 6:
METABOLISM AND ENERGY MTChem2:Biochemistry for MLS
(Lecture)
PRODUCTION College A.Y. 2021 – 2022 – 2

3. CITRIC ACID CYCLE


OUTLINE  Acetyl CoA will be used in 3rd and 4th stage.
4. ELECTRON TRANSPORT CHAIN AND
I. Recall: Overview of Energy Production
a. Digestion
OXIDATIVE PHOSPHORYLATION
b. Acetyl CoA formation
c. Citric Acid Cycle  Occurs Intracellular, specifically in mitochondria
i. Steps 1 to 8  Common metabolic pathway
d. Electron Transport Chain o this is the sum of the biochemical reactions of the
i. Steps 1 to 4 CAC, ETC and OP.
ii. Oxidative Phosphorylation
II. Synthesis and Summary

OVERVIEW OF BIOCHEMICAL ENERGY


PRODUCTION

1. DIGESTION
 Not part of metabolism since it happens outside the cell
or in Extracellular. But metabolic processes happen
intracellular or inside the cell. Digestion is part of the
process since this is where metabolism start where it
begins in the;
o Mouth → stomach → small intestines (has specific
enzymes which digest the food which are
carbohydrates, lipids and proteins.
o End products: building blocks THE CITRIC ACID CYCLE
 Monosaccharides
 Fatty Acids + Glycerol  Citric acid cycle = based on its first intermediate product
 Amino Acids produced which is citric acid/citrate
 Also known as:
o Kreb Cycle = discoverer Hans Adolf Krebs
o Tricarboxylic Acid Cycle = due to presence of 3
carboxylate groups present in citric acid;

 Series of enzyme-catalyzed reactions that occur in the


mitochondria; Each step in your series is enzyme-
catalyzed.
 Series of biochemical reactions in which the acetyl
portion of acetyl CoA is oxidized to carbon dioxide and
2. ACETYL COA FORMATION the reduced coenzymes (FADH2 and NADH) and energy
in the form of GTP are produced;
 Where numerous reactions takes place.
 Occurs in cytosol and mitochondria
o the small molecules produced from stage 1 are
further oxidized and finally forms two acetyl units
which attaches to coenzyme a to produce acetyl
coenzyme a and the reduced NADH. (End Product:
Acetyl CoA)
 Primary products:
o 2-C acetyl units→ Acetyl CoA + NADH

o Red Circles are the mentioned products.

 Comprises the third stage of the catabolism of


biomolecules to carbon dioxide, water and energy;
 Cyclic metabolic pathway that begins with the
addition of acetyl CoA to four-carbon substrate

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MODULE 6: METABOLISM AND ENERGY PRODUCTION

and ends when the same four-carbon compound


is produced as a product; and the cycle repeats itself.
o From stage 1 Acetyl CoA will enter from stage 2 then
it will repeat its reaction until step 1.

8 STEPS OF KREBS CYCLE


 There are a total of 8 steps in the krebs cycle and
produces high energy compounds for ATP synthesis
needed in your stage 4.

STEP 2: FORMATION OF ISOCITRATE


 From step one which is citrate, is then converted to
form cis- Aconitate with the help of the enzyme
aconitase. In this reaction there was a loss of water,
therefore the first part or substep is called dehydration.
 Next, your cis-aconitate would be further react with the
addition of water to form its less symmetrical isomer
called your isocitrate. In this case, you add a water in a
reaction and that is called hydration which is the
second part of the reaction.
 For step two, we have two sub step.

WHAT YOU NEED TO REMEMBER IN KREBS CYCLE


 Name of the reactions
 Enzymes involved
 Reactants and products produced in each step

Note: No need to memorize the structure, but this will serve


as a guide for better understanding

STEP 1: FORMATION OF CITRATE


 The krebs cycle starts with oxaloacetate combining with DIFFERENCE OF CITRATE AND ISOCITRATE
acetyl coenzyme a which came from the stage 2.
 When you combine the two you’ll be able to form your  The structure of the citrate and isocitrate is similar but
Citryl Coenzyme A. This reaction alone is called your the difference is in the attachment of their hydroxyl
condensation. This reaction alone use an enzyme group and hydrogen to the respective carbon.
called your citrate synthase.  This is called isomerization which means you have the
 In this specific step, you already have a sub step which same atoms but with a different arrangement that is why
is the condensation. it is called isocitrate because of the rearrangement of
 Your formed Citryl CoenzymeA reacts with water to form the atoms.
your citrate and co-enzyme A which are the final  We need to rearrange it because citrate is a tertiary
products of your step one. alcohol and isocitrate secondary alcohol, and secondary
 Remember that; your citric acid cycle was named as alcohols are easier to oxidize. And we need a product
such because the first intermediate product form which that is easier to oxidize because our next step is
oxidation.
is the citric acid or citrate. This second process is called
hydrolysis because it involved water and it was also
catalyzed by the same enzyme called citrate synthase.
 This reaction resulted to the combination of your acetyl
group from acetyl coenzyme A aand oxaloacetate until
it’s able to form a 6 carbon citrate and 3 Coenzyme A.
 Take note: There are 2 parts of this step, the first is the
condensation of your acetyl coenzymeA and
oxaloacetate to form your citryl coenzyme A and the
second part is the hydrolysis of the thyroester bond and
your citryl coenzyme A to produce citrate and coenzyme
a. Both are catalyzed with enzyme citrate synthase.

STEP 3: OXIDATION AND DECARBOXYLATION


 It is also known as the Oxidation of Isocitrate and
formation of carbon dioxide.

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MODULE 6: METABOLISM AND ENERGY PRODUCTION

 This step is the first redox reaction or oxidation exhalation and your coenzyme reacts with the
reduction in the citric acid cycle. decarboxylation product producing succinyl coenzyme
 This reaction involves the following: A which is a four carbon substrate.
o First your isocitrate which came from step 3 is  In this step, you are able to have two substep; oxidation
oxidized into oxalosuccinate, a ketone, by the help of and decarboxylation. These two substeps occur
the coenzyme NAD which served as your oxidizing simultaneously and the enzyme used in this step is
agent in this case and it was also catalyzed by the alpha ketoglutarate dehydrogenase complex.
enzyme isocitrate dehydrogenase.  End products: 1 NADH and 1 Carbon dioxide
o Second, once your NAD is used up it will now  Key points:
become reduced NAD and also one free hydrogen  A second NAD+ is used and converted into its
ions. Any reaction that uses oxidizing agent, reduced from NADH
automatically it is called oxidation.  A second carboxyl group was also removed s
o Third, your oxalosuccinate remains bound to the carbon dioxide.
same enzyme which is isocitrate dehydrogenase and  Coenzyme A reacts with the decarboxylation to
undergoes your decarboxylation. Decarboxylation produce succinyl CoA. This is the Second
means the loos of carbon dioxide so this process involvement of Coenzyme A in the cycle. (First
means the release of carbon dioxide and the involvement: Step1)
formation of your 5 carbon mmolecule alpha-
ketoglutarate.
o In this specific step we have two sub steps; oxidation
and decarboxylation. In oxidation, you have used
your oxidizing agent, NAD and reduced to NADH.
While in decarboxylation, you have converted your
oxalosuscinate into alpha ketoglutarate and also
released Carbon dioxide through exhalation and both
these substeps use the same enzyme isocitrate
dehydrogenase.

 End products: 1 NADH and 1 Carbon Dioxide


 Key points:
 In step 3, your isocitrate which came from steo two
is a secondary alcohol and was easily converted
into oxalosuccinate, a ketone, through oxidation. STEP 5: THIOESTER BOND CLEAVAGE IN
 NAD+ is converted into its reduced form NADH. SUCCINYL COA AND PHOSPHORYLATION OF
 A carboxyl group from oxalosuccinate is removed GDP
as carbon dioxide through decarboxylation.  5th step is the phosphorylation, the whole reaction is
catalyzed by the enzyme succinyl coenzyme A
synthetase.
 First, the succinyl coenzyme A which camee from your
previous step is converted into succinyl phosphate, a
free coenzyme A is produced in this reaction. Therefore,
the first product of this reaction is the coenzyme A.
 Next, the phosphoryl group present in the succinyl
phosphate is then transferred to GDP or guanosine
diphosphate and when you add another phosphate in
this molecule you’ll be able to form your GTP or
guanosine triphosphate.
 The process of transferring phosphoryl group is called
phosphorylation, as mentioned in the previous part
and the GTP functions the same as ATP, its just that
their nitrogen base is different.
 End products: GTP and Succinate
STEP 4: OXIDATION OF ALPHA-KETOGLUTARATE  Keypoints:
AND FORMATION OF CO2  Thee enzyme synthase from step 1 is differenr from
 2ND Redox reaction the enzyme synthetase from step 5
 This involves the following:  Synthetase uses energy from the breaking of a high
o One molecule of NAD, coenzyme A, and alpha- energy phosphate bond.
ketoglutarate which came from the previous step.
 The catalyst in this step is a three enzyme system called
your alpha ketoglutarate dehydrogenase complex.
This three enzyme complex is composed of b
vitamin thiamine in the form of thiamine
pyrophosphate and magnesium ions.
 Same with step 3, it involves your oxidation and
decarboxylation but the difference between the two is
that unlike in the step 3 here in step 4 your oxidation and
decarboxylation occurs simultaneously.
 So in this case, NAD which is still the oxidizing agent is
converted to its reduced form which is NADH , the first
product.
 Then, a second carboxyl group is r removed as carbon
dioxide just like in step 3 and is released through

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MODULE 6: METABOLISM AND ENERGY PRODUCTION

STEP 6: OXIDATION OF SUCCINATE SYNTHESIS AND IMPORTANT NOTES IN CITRIC


 3rd redox reaction in the citric acid cycle ACID CYCLE
 Succinate from the previous step will be combined with
oxidizing agent FAD or flavine adenine dinoclutide and
then our enzyme involve here is succinate
dehydrogenase.
 As you can see in the succinate, there are highlighted
red, these red hydrogen would combine with FAD,
leaving succinate forming FADH2 or reduced FAD.
 Then your succinate since there is a loos in Hydrogen
ions it would become Fumarate, a 4 carbon substrate
also known as trans-double bond. (Trans- opposite
side of molecules are present))
 End product: 1 FADH2
 Keeypoints:
 Product in step 6 is a reduced form of Flavin
adenine dinucleotide

ELECTRON TRANSPORT CHAIN

 4th stage in metabolism.


 Also frequently called as respiratory chain.
o It is called as respiratory chain because it has
STEP 7: HYDRATION OF FUMARATE
Oxygen (O2) on it.
 This catalyzes the addition of water to the double bond
 a multistep process that relies on four enzyme systems
of fumarate. You are able to form the isomer of the
as well as mobile electron carriers;
product which is malate.
 a series of biochemical reactions in which electrons and
hydrogen ions from NADH and FADH2 are passed to
STEP 8: OXIDATION OF L-MALATE TO intermediate carriers and then react with molecular
REGENERATE OXALOSUCCINATE oxygen to produce water. (End result: to produce H2O)
 4th redox reaction in the citric acid cycle o NADH and FADH2 are oxidized in this process to
 NAD which serve as an oxidizing agent, it will combine form water;
or react with malate which came from the previous step,  The complexes are situated in the inner membrane of
picking up 2 hydrogen atoms, lleaaving malate and you’ll the mitochondria, arranged so that electrons can be
be able to form reduce NAD and hydrogen atom. For passed to progressively stronger oxidizing agent;
you to be able to produce that, the enzyme or catalyzed o Same with Kreb Cycl. Both Kreb Cycle and ETC are
here in this reaction is called malate dehydrogenase. found in mitochondria.
 As mentioned earlier, hydrogen atoms present on
malate and NAD forming reduce NAD and free hydrogen
atom and forming again regenerated oxaloacetate.
 After this, the cycle repeats again as long as you can
still regenerate ooxaloacytate and acetyk coenzyme A.

TOTAL PRODUCTS PRODUCED IN CITRIC ACID


CYCLE
 2 Carbon dioxide
 3 NADH
 1 FADH2
 1 GTP FOUR COMPLEXES OF ETC
SUMMARY  These four protein complexes, which are tightly bound to
the membrane, are:

1. Complex I: NADH-coenzyme Q reductase

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MODULE 6: METABOLISM AND ENERGY PRODUCTION

2. Complex II: Succinate-coenzyme Q reductase\


o As you can see in our reaction, we will start with the
reducing agent NADH which came from Kreb cycle
and after that it will undergo oxidation (it will come
back as NAD+). This NAD can be used as oxidizing
agent in our Kreb Cycle. The removed Hydrogen
from NADH would be combining with your FMN
(Flavin mononucleotide) and would undergo
reduction to be able to form FMNH2 (or reduced
form). This reduced form of FMN would undergo
several redox processes until such time that it would
now reach your CoQ or Coenzyme Q. This CoQ will
3. Complex III: Coenzyme Q-cytochrome c reductase undergo reduction process where it will form your
reduced form of Coenzyme Q or CoQH2 which will be
used in Complex III. Once reduced, your CoQ will be
able to form again your reduced form which is CoQH2
and will be used again in complex II.

4. Complex IV: Cytochrome c oxidase

COMPLEX II: SUCCINATE-COENZYME Q


REDUCTASE

 Complex II contains only four protein subuints.


 This complex is similar to complex I but instead of NADH
as starting material, FADH2, the coenzyme generated in
 The oxygen involved in the water formation associated the citric acid cycle when succinate is converted to
with the electron transport chain is the oxygen that is fumarate, is used. That is why the term “succinate” is in
inhaled during the human breathing process. And the name of complex II.
because oxygen is needed, ETC is an aerobic o FADH2 will be used as starting material in Complex II
pathway. (which came in our Kreb Cycle), when Succinate is
o In complexes, you can already know the starting converted into Fumarate that is why the name of
material and end product in that complex by looking complex II is Succinate since it came from FADH2. As
at their names. mentioned, the process is same with Complex I.
From FADH2 it would undergo Oxidation and it would
FOUR COMPLEXES IN ELECTRON TRANSPORT become FAD (oxidizing agent) and it goes back in
CHAIN Kreb Cycle to be used again in step 6. The removed
Hydrogen will undergo several redox processes and
COMPLEX I: NADH-COENZYME Q REDUCTASE it will go to Coenzyme Q.
o Same end products with Complex I and Complex II
 NADH, from the citric acid cycle, is the source for the which is CoQH2
electrons that are processed through complex I.
o Your starting material will be the reducing agent
which is the reduced NADH from citric acid cycle.
 This is the largest of the four protein complexes. Since
it contain more than 40 protein subunits
 The result of electron movement in complex I is the
transfer of electrons from NADH to coenzyme Q
(CoQ), a reason why the name of complex I is NADH–
coenzyme Q reductase.
 Complex I involve the interaction of NADH with flavin
mononucleotide (FMN).
 The NADH is oxidized to NAD+ (which can again be used
in the citric acid cycle) as it passes two hydrogen ions and
two electrons to FMN, which is reduced to FMNH2.

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MODULE 6: METABOLISM AND ENERGY PRODUCTION

Copper and Iron centers until such point it would


meet your Oxygen from inhalation or breathing. Your
electrons which has your Hydrogen atom will
combine with Oxygen to form water. The end product
of Complex IV and ETC will be 2H2O.

SUMMARY OF ETC

COMPLEX NAME NO. OF PROSTHETIC


PROTEINS GROUP
COMPLEX III: COENZYME Q-CYTOCHROME C
I NADH-CoQ >40 FMN
REDUCTASE Reductase
 Complex III contains 11 different protein subunits. II Succinate-CoQ 4 FAD
 Electron carriers present in this complex include several Reductase Cyt b
iron–sulfur (FeS) proteins as well as several III CoQ-Cyt c 11 Cyt b
cytochromes. Reductase Cyt c
Fe-S centers
IV Cyt c Oxidase 13 Cyt a
CYTOCHROME Cyt a3
 a heme-containing protein in which reversible oxidation Cu-Fe centers
and reduction of an iron atom occur.  Note: Para di malito yung unang name is their starting
o Need of cytochrome since you have iron-sulfur material and yung kasunod will be their end product.
proteins in complex III.
KEYNOTES:
 The initial substrate for complex III is CoQH2 molecules 1. Complexes I and II produce a common product,
(which came from Complex I and Complex II) carrying the the reduced form of coenzyme Q (CoQH2) which will be
electrons that have been processed through complex I used in complex III.
(from NADH) and also those processed through complex
II (from FADH2). 2. NADH and FADH2 are reducing agents and when
 The end result will be on Cyt c, which can move they donate electrons, they are oxidized. When NADH
laterally in the intermembrane space; donates two electrons, it is oxidized to NAD+, which can re-
o Cyt c (Cytochrome c) delivers its electrons to enter the citric acid cycle. Likewise, when FADH2 donates
complex IV. two electrons, it
is oxidized to FAD, which can be used as an
oxidant in step [6] of the citric acid cycle once
again.

3. Coenzyme Q, in both its oxidized and reduced forms, is


lipid soluble and can move laterally within the mitochondrial
membrane. Its function is to shuttle its newly acquired
electrons to complex III, where it becomes the initial
substrate for reactions at this complex. The Q in the
designation coenzyme Q comes from the name quinone.
Structurally, coenzyme Q is a quinone derivative.
o As you can see in our reaction, our starting material
is the CoQH2 reduced form and it would undergo 4. There are other cytochromes involved in complex III but
several electron movements. The end product will be Cyt c is the only one that is water soluble and the only one
cytochrome (cyt c) which will be used in complex IV. that can travel and deliver electrons.

COMPLEX IV: CYTOCHROME C OXIDASE

 Complex IV contains 13 protein subunits.


 Electron movement flows from starting material cyt c
(carrying electrons from complex III) to cyt a to cyt a3.
 In the final step of electron transfer, the electrons
combine with oxygen (O2) to form water.
 Electrons pass through both copper and iron centers
and in the last step interact with molecular O2.
 At the end of the chain, the electrons and protons react
with inhaled oxygen to form water and the whole process
for ETC is complete.

OXIDATIVE PHOSPHORYLATION (OP)

OXIDATIVE PHOSPHORYLATION

 is the biochemical process by which ATP is synthesized


from ADP as a result of the transfer of electrons and
o As you can see in our reaction, our starting material hydrogen ions from NADH or FADH2 to O2 through the
will be Cytochrome C (Cyt C) and then it will jump to electron carriers involved in the electron transport chain.
different electron movement which involves the o PRODUCT: ATP as a source of energy

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MODULE 6: METABOLISM AND ENERGY PRODUCTION

 You have your Complex I, II, III, IV and beside is your ATP
where Oxidative Phosphorylation takes place. Since you
have several electron movements, processing of ADP to
ATP occurs as well as the Oxidative Phosphorylation.

HOW DOES OP WORK?

 OP is simply the production of ATP but its process is still


complex. H+ ions generated by reactions in the ETC, as
well as H+ ions present in the matrix of the mitochondria,
are pumped across the inner mitochondrial membrane
into the intermembrane space at three different sites. This
process requires energy, since it moves protons against
the concentration gradient. The energy comes from redox STAGES STARTING END LOCATION ENERGY
reactions in the electron transport chain. MOLECULE PRODUCT SHUTTLED
 To return to the matrix, the H+ ions travel through a TO OP
channel in the ATP synthase enzyme. ATP synthase is Krebs
the enzyme that catalyzes the phosphorylation of ADP to Cycle Acetyl CoA Carbon Matrix of Reduced
(CAC) (which came dioxide Mitochondria NADH and
form ATP. The energy released as the protons return to
from Stage FADH2
the matrix converts ADP to ATP. 2)
 Oxidative phosphorylation is not the only process by ETC Electrons ATP, H2O Inner
which ATP is produced in cells. A second process, (carried out (They membrane
substrate phosphorylation, can also be an ATP source. by NADH believed of
However, the amount of ATP produced by this second and FADH2) that OP is mitochondria
process is much less than that produced by oxidative included in
phosphorylation. ETC that’s
why there
is atp)
SUMMARY OF ELECTRON TRANSPORT CHAIN OP Electrons ATP Inner
AND OXIDATIVE PHOSPHORYLATION membrane
of
 The four enzyme complexes (I–IV) of the electron mitochondria
transport chain are located within the inner membrane of
a mitochondrion, between the matrix and the END PRODUCTS ACETYL CoA TOTAL PRODUCTS
intermembrane space.
 Electrons enter the chain when NADH and FADH2 are 2 CO2 2 4 CO2
oxidized and then transported through a series of 3 NADH 2 6 NADH
complexes along the pathway shown in red arrows. 1 FADH2 2 2 FADH2
 The electrons ultimately combine with O2 to form H2O.
1 GTP 2 2 GTP
 Protons (H+) are pumped across the inner membrane into
*Lahat to naform sa isang cycle.
the intermembrane space at three locations shown by
blue arrows. 2 Acetyl CoA = Products?
 The energy released when protons return to the matrix by 1 Acetyl CoA = 1 cycle
traveling through a channel (in green arrow) in the ATP
synthase enzyme is used to convert ADP to ATP.

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MODULE 6: METABOLISM AND ENERGY PRODUCTION

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Module 7: MTChem2:Biochemistry for MLS
Carbohydrate, Protein & Lipid Metabolism (Lecture)
College A.Y. 2021 – 2022 – 2

 Pancreatic α-amylase breaks down polysaccharide


OUTLINE chain into shorter and shorter segments until the
I Carbohydrate Metabolism disaccharide maltose and glucose are the dominant
A Digestion of Carbohydrates species.
B Glysolysis  Final step in carbohydrate digestion occurs on the outer
II Glycogen membranes of intestinal mucosal cells.
III Gluconeogenesis
A Cori Cycle  Important disaccharidase enzymes are maltase,
B Pentose Phosphate Pathway sucrase, and lactase.
IV Hormonal Control of Carbohydrate Metabolism o These enzymes hydrolyze the disaccharides to
A Insulin convert them into monosaccharides.
B Glucagon o Example: the disaccharide maltose upon the action
C Epinephrine of maltase, it will be broken down into two glucose
V B Vitamins and Carbohydrate Metabolism molecules.
A Biotin
B Vitamin B6
o Note: for sucrose and lactose, they cannot be
metabolized into simpler units unless they reach
digestion by the intestinal mucosal cells.
 Three major broken-down products: glucose, galactose
CARBOHYDRATE (CHO) METABOLISM
and fructose
 Carbohydrates are considered go foods. Our bodies need
 Protein Carriers mediate the passage of the
those go foods in order to produce energy. Energy in the
monosaccharides through the cell membrane.
form of ATP is needed to sustain bodily functions.
o Once the major breakdown products are obtained,
 Molecules of glucose is the focal point of carbohydrate
this can be absorbed to the bloodstream through the
metabolism.
intestinal wall found in these intestinal walls are the
o Glucose molecule is also known as the blood sugar structures that we call BLOODSTREAM.
because this is the monosaccharide that is readily
 Villi – responsible for the absorption process
utilized by the body cells. Glucose is normally found
thru active transport.
in the bloodstream because of the fact that all cells
in our body use glucose.  Monosaccharides are transported to the liver where
 Glucose is either oxidized to yield energy or stored as fructose and galactose are rapidly converted to glucose.
glycogen. o Same pathway as the glucose : glycolytic pathway
o Glucose is stored as glycogen when the blood
glucose level is already high. Thus, they will convert Quick Check!
your glucose units into a storage form and that is * the location within the human body where each of the
glycogen. following aspects of carbohydrate digestion occurs
 Sufficient Oxygen: glucose is totally oxidized to CO2
and H2O. A. Intestinal Mucosal Cells
 Absence of Oxygen: glucose is only partially oxidized to o The enzyme sucrase is active
lactic acid. o The monosaccharides glucose, fructose, and
o Example: muscle soreness is common among galactose are produced.
athletes; this is because of the accumulation of lactic B. Small Intestine
acid; happens in strenuous activities. o Hydrolysis reactions converting polysaccharides to
disaccharides occur
DIGESTION OF CARBOHYDRATES C. Mouth
o First site where breaking of glycosidic linkages
DIGESTION occurs
 Process in a nutshell: We eat food, this food is a very
huge polymer that still has to be broken down into smaller SUMMARY OF CARBOHYDRATE DIGESTION IN
units. Those polymers must be converted into
THE HUMAN BODY
monosaccharides. For example, glucose, glucose will
then be capable of being utilized by the body’s cells. After
undergoing proper metabolism, the glucose molecules
will be synthesizing energy and other end products.
 Biochemical process by rich food molecules, through
hydrolysis, are broken down into simpler chemical units
that can be used by the cells for their metabolic needs.
 Begins in the mouth, where the enzymes Salivary α-
amylase catalyzes the hydrolysis of α-glycosidic linkage.
o When these glycosidic linkages are broken down,
free glucose units cannot be utilized by the body.
However, only a small amount of carbohydrate
digestion occurs in the because food is swallowed
quickly.
 Although majority of what we eat spends more time in the
stomach, very little further carbohydrate digestion occurs
in the stomach. Because the stomach does not contain
any carbohydrate-digesting enzymes.  First: Dietary Carbohydrates which are very large
 Primary site of carbohydrate digestion is within the small molecules. They will be entering the mouth(1), where in
intestine, where α-amylase is secreted by the pancreas. the salivary α-amylase we will be hydrolyzing some of
the glycosidic linkages present in these carbohydrates.

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MODULE 7: CARBOHYDRATE, PROTEIN & LIPID METABOLISM

 Second: The carbohydrates will now be converted into Step 2: Involves the conversion of glucose 6-phosphate into
smaller polysaccharides or possibly maltose, sucrose, fructose 6-phosphate upon the action of
and lactose. These products will then be going to the phosphoglucoisomerase.
stomach(2). However, in the stomach there will be no
digestion that will occur because the gastric juices, they Step 3: Fructose 6-phosphate upon the action of
do not exert any effect on digestion. phosphofructokinase and ATP, will be converted into
 Third: Once those products have reached the small fructose 1,6-biphosphate.
intestine(3), there will be pancreatic digestive enzymes,
which are responsible for the hydrolysis of
polysaccharides to disaccharides.
o The remaining polysaccharides, after being broken
down by the pancreatic enzymes, will now be present
as disaccharides; maltose, sucrose, and lactose.
 Fourth: These disaccharides will now travel to the
intestinal mucosal cells(4), wherein we have 3 enzymes
that can break down these disaccharides. So, we have:
o Maltese → converting maltose into 2 glucose units
o Sucrase → converting sucrose into glucose and
fructose
o Lactase → converting lactose into glucose and
galactose
 Fifth: Now that we have these monosaccharides, they will
the be present in the bloodstream after active transport
in the intestinal lining(5), where the villi are located.
Step 4: Fructose 1,6-biphosphate will be cleaved into two.
GLYCOLYSIS These products will then be dihydroxyacetone phosphate
and glyceraldehyde 3-phosphate. The glyceraldehyde 3-
WHAT HAPPENS IN GLYCOLYSIS? phosphate can readily enter or proceed with the glycolytic
 Glucose is converted into 2 molecules of pyruvate (a C3 pathway. However, for dihydroxyacetone phosphate it still
molecule), chemical energy in the form of ATP is has to undergo a conversion process into glyceraldehyde 3-
produced; and NADH is produced. phosphate also.
 A Linear Pathway that functions in almost all cell.
 An oxidation process Step 5: Entails the conversion of dihydroxyacetone
 Oxidizing Agent: Coenzyme NAD+ (nicotinamide phosphate into glyceraldehyde 3-phosphate. The enzyme
needed for that is triosephosphate isomerase.
adenine dinucleotide)
 Anaerobic Pathway – it doesn’t require oxygen in order to
Step 6: The glyceraldehyde 3-phosphate molecules will be
carry out the process
undergoing oxidation and phosphorylation, in order to
 Aka “Embden-Meyerhof Pathway”
produce 1,3-biphosphoglycerate. The enzyme needed for
 All enzymes needed for Glycolysis are present in the cell this step is glyceraldehyde 3-phosphate dehydrogenase.
cytosol
 2 stages Step 7: The 1,3-biphosphoglycerate will be converted into 3-
o 6-carbon stage phosphoglycerate. The enzyme needed for this step is
o 3-carbon stage phosphoglycerokinase.

OVERVIEW OF GLYCOLYSIS

Step 8: The 3- phosphoglycerate molecule will be


undergoing isomerization to become 2-phosphoglycerate.
Step 1: Entails the conversion of glucose into glucose 6- The enzyme needed for that process to occur is
phosphate upon the action of hexokinase. Aside from that, phosphoglyceromutase.
this is an energy consuming process because it needs ATP.
Step 9: An alcohol dehydration reaction. The two
phosphoglycerate molecule will be converted into

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MODULE 7: CARBOHYDRATE, PROTEIN & LIPID METABOLISM

phosphoenol pyruvate upon the action of the enzyme membrane. It also changes glucose from a neutral
enolase. molecule to a negatively charged substance, and
having this negative charge limits the ability of
Step 10: The phosphoenolpyruvate molecule will be phosphorylated molecules to cross the cell
converted into pyruvate. Aside from that, the phosphate membrane.
group of phosphoenolpyruvate will be transferred to ADP in
order to produce ATP.

GLYCOLYSIS : SIX-CARBON STAGE STEP 2 – ISOMERATION: FORMATION OF


 Energy-consuming stage. FRUCTOSE-6-PHOSPHATE
 Conversion of 2 ATP molecules to 2 ADP molecules is  Glucose-6-phosphate is isomerized to fructose 6-
used to transform monosaccharides into monosaccharide phosphate
phosphates.  At this stage we do not synthesize a new molecule but
 Intermediates: Glucose or Fructose derivatives. instead only isomerization of the glucose 6-phosphate
o But in these derivatives there are phosphate groups occur. So, there would only be a rearrangement in the
that are attached to them atoms present in our molecule.
 This stage involves three steps that utilizes a glucose or  Enzyme: Phosphoglucoisomerase
fructose molecule; both of these has six carbon atoms in  C1 of the glucose is no longer part of the ring structure
their structures.
o The difference is glucose is an aldose, while fructose
is a ketose.

 Isomerization: with the help of an isomerase enzyme.


o In this case, we have phosphoglucoisomerase.
There is a rearrangement of the atoms in the
STEP 1: PHOSPHORYLATION USING ATP:
glucose molecule that will happen and this will result
FORMATION OF GLUCOSE-6-PHOSPHATE to a new chemical structure.
 Begins with phosphorylation of glucose to yield glucose- o So, from an original 6-membered ring, glucose it was
6-phosphate isomerized into a five-membered ring which is
 Addition of phosphate group to the glucose molecule. fructose. But still fructose has 6 carbon atoms.
 The phosphate group is attached at the hydroxyl oxygen
of carbon #6. This is the carbon found outside the ring. STEP 3 – PHOSPHORYLATION USING ATP:
The Phosphate group is from an ATP molecule; FORMATION OF FRUCTOSE-1,6-BIPHOSPHATE
 Enzyme: Hexokinase  ATP is the source of the phosphate energy.
 Requires Mg2+ ion for its activity  Similar process on step 1; there will be another
o Activates hexokinase phosphate group added to fructose-6-phosphate upon
the action of phosphofructokinase.
 Enzyme: Phosphofructokinase
 Thus, Fructose molecule now contains 2 phosphate
groups.
 End product: fructose-1,6-biphosphate

Is biphosphate similar to diphosphate? It’s both yes and no


 Since there will be a utilization of energy from ATP, it will
be converted into ADP. The phosphate group that came  Yes, because both are referring to having two phosphate
from the ATP molecule is now attached to the glucose groups.
molecule; at the hydroxyl oxygen of carbon #6.  No, because the term biphosphate refers to having two
 Why is phosphate group added to the glucose molecule? phosphate groups attached at different atoms as seen in
o For glucose to be utilized by the cells it has to be the illustration. On the other hand, diphosphate refers to
inside the cell. However, the cell membrane is semi- having two phosphate groups that are directly linked with
permeable, it can control what goes in and what goes each other on the same atom.
out of the cell. Glucose is one of the molecules which o Example:
can cross the cell membrane. Adenosine Diphosphate, where two phosphates are
o Phosphorylation of glucose or the addition of linked together by phosphoanhydride bond.
phosphate to the glucose molecule provides a way of
trapping glucose within the cell.
o The end product here which is glucose 6-
phosphate, it can no longer cross the cell

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 From Fructose 6-phosphate, we will be adding a molecule


of phosphate at carbon number 1. This reaction is
catalyzed by phosphofructokinase which also requires
magnesium ion for its activity.
 Take note: There are already 2 enzymes that requires
Magnesium ion, these are in the step 1: hexokinase and
step 3: phosphofructokinase.
 End product: Fructose 1,6-biphosphate  As you can see, the contents of the upper half and lower
o It now has phosphate group at carbon #1 and half of the fructose 1,6-biphosphate are not identical; they
carbon #6 are unsymmetrical.
 For Dihydroxyacetone phosphate, the carbonyl group is
GLYCOLYSIS: THREE-CARBON STAGE found in the middle of the structure. Making it a ketone.
 Energy – generating stage  For Glyceraldehyde 3-phosphate, the carbonyl group is
 Intermediates: found at a terminal location.
o C3 – phosphates (2 of which are high-energy
species)
o All phosphorylated derivatives of STEP 5 – ISOMERIZATION: FORMATION OF
dihydroxyacetone, glyceraldehyde, glycerate, GLYCERALDEHYDE-3-PHOSPHATE
pyruvate – derivatives of either Glycerol or Acetone.
 Loss of phosphate effects the conversion of ADP  Glyceraldehyde 3-phosphate is a glycolysis intermediate.
molecules to ATP molecules.  Dihydroxyacetone phosphate
o Readily converted into glyceraldehyde 3-phosphate
(isomer).
 Why does dihydroxyacetone the only one that needs to
undergo isomerization?
o It is because glyceraldehyde 3-phosphate can
readily enter the rest of the glycolytic pathway whilst
dihydroxyacetone cannot.
 Enzyme: Triosephosphate isomerase

 The end product for step 5 is another molecule of


glyceraldehyde 3-phosphate. So now, we have 2
glyceraldehyde 3-phosphate molecules in the glycolytic
pathway.

STEP 6 – OXIDATION AND PHOSPHORYLATION


STEP 4 – CLEAVAGE: FORMATION OF 2 TRIOSE USING Pi : FORMATION OF
PHOSPHATES 1,3-BIPHOSPHOGLYCERATE
 The reacting C6 species is split into two C3 (triose)  Note: starting from step 7-10 bear in mind that we have
species. two separate glyceraldehyde 3-phosphate molecules.
o C6 species before step 4 is fructose 1,6-  A phosphate group is added to glyceraldehyde 3-
biphosphate. phosphate to produce 1,3-biphosphoglycerate.
 2 trios being produced are not identical because  The hydrogen of aldehyde group becomes part of NADH
fructose 1,6-biphosphate is unsymmetrical.  The source of the added phosphate is inorganic
 Products: phosphate (Pi)
o Dihydroxyacetone phosphate  Enzyme: Glyceraldehyde 3-phosphate
o Glyceraldehyde 3-phosphate dehydrogenase
 Enzyme: Aldolase

 High energy phosphate – these are phosphate groups


attached to a carbon atom that is also involved in a
carbon-carbon or carbon-oxygen double bond.

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 When the hydrogen of the aldehyde group is bonded into


NAD, part of this reaction will be the reduction of NAD to
NADH.
 End products: 1,3-biphosphoglycerate, NADH, H+

STEP 7 – PHOSPHORYLATION OF ADP:


FORMATION OF 3-PHOSPHOGLYCERATE
 The biphosphate species form is converted back to
monophosphate species.
 ATP producing step.
 C1 phosphate group of 1,3-biphosphoglycerate is
transferred to an ADP molecule to form the ATP.  For 2-phosphoglycerate, we removed a water molecule,
 Enzyme: Phosphoglycerokinase as you can see in the product side. After losing the
hydrogen of C2 and hydroxyl of C3, there are 3 electrons
for carbon. That is why another bond was formed
between them. Thus, there will be another set of double
bond and that is between C2 and C3.
 Do we consider 2-phosphoglycerate a high-energy
phosphate compound?
o No, because a high-energy phosphate compound
should have a phosphate group attached to an atom
of carbon, that is also involved in carbon-carbon or
 So, what happens here is that in 1,3-biphosphate carbon-oxygen double bond.
o In the case of 2-phosphoglycerate, the phosphate
molecule, the phosphate group attached at C1 will be
group is only attached to a carbon atom involved in
transferred to ADP molecule to form ATP molecule upon
single bonds. Therefore, 2-phosphoglycerate is not
the action of phosphoglycerokinase.
a high-energy phosphate compound.
 ATP production involves substrate-level
phosphorylation  The end product phosphoenolpyruvate is considered
high-energy phosphate compound because of the double
o ATP is produced from ADP through direct transfer of
bond formed at C2 and C3.
a high-energy phosphoryl group from a reaction
substrate to ADP.

STEP 8 – ISOMERIZATION: FORMATION OF 2- STEP 10 – PHOSPHORYLATION OF ADP:


PHOSPHOGLYCERATE FORMATION OF PYRUVATE
 Substrate level phosphorylation occurs again
 Phosphate group of 3- phosphoglycerate is moved from
C3 to C2.  Phosphoenolpyruvate transfer its high-energy for its
 Enzyme: Phosphoglyceromutase phosphate group to an ADP molecule to produce ATP
and pyruvate.
 Rearrangement of phosphate group
 Enzyme: Pyruvate kinase
 Requires both Mg2+ and K+
 2 ATP molecules are produced

STEP 9 – DEHYDRATION: FORMATION OF


PHOSPHOENOLPYRUVATE
 Similar to step 6; the end product of step 9 is another
high-energy phosphate compound
 Alcohol dehydration reaction NET OVER ALL EQUATION
o Removing a molecule of water
 Result is another compound containing a high energy
phosphate group.
 Enzyme: Enolase
 Requires Mg2+

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 Net is +2 per glucose molecule o The signal for the hexokinase action is the level of
o Meaning every glucose molecule we have we are glucose 6-phosphate. When hexokinase sensed that
generating 2 ATP molecules the levels of glucosee 6-phoshpate is high, it will
temporarily stop performing its function, therefore
stopping glycolysis temporarily .
ENTRY OF GALACTOSE AND FRUCTOSE INTO  Step 3:
GLYCOLYSIS o For step 3, fructose 6-phosphate is converted to
 When digestion occurs, the polysaccharides are being fructose 1,6-biphoshphate by phosphofructokinase.
broken down into glucose, galactose and fructose. So, this is inhibited by high concentrations of ATP
 As discussed, glucose can readily enter the glycolytic and Citrate.
pathway however, for a galactose and fructose they still o So when there is a high ATP, meaning high energy,
have to undergo conversion into intermediates that are it means the rate of energy consumption is low; the
present in the glycolytic pathway so that they can enter energy is high because the energy is not being
the glycolytic pathway also and be metabolized. used.
 So for galactose, galactose begins with its conversion to o Possible that your energy concumption is low
glucose one phosphate. However, glucose 1-phosphate because you are just laying on bed all day so there
cannot undergo or cannot enter the glycolytic yet so is high ATP at this state. This increased level of ATP
glucose 1-phosphate still has to undergo further serves as the signal to temporarily stop the function
conversion into glucose 6-phosphate, and then this of phosphofructokinase. Aside from an increased
glucose 6-phosphate can then enter the glycolytic ATP, glucose 6-phoisphate level also increases
pathway at which step at step 2.  Step 10:
 So at Step 2, glucose 6 phosphate will undergo o For the last mechanism, this involves step 10
isomerization into fructose 6-phosphate. Then, this will conversion of phosphoenolpyruvate to pyruvate by
already proceed up to the step 10 of the glycolytic pyruvate kinase.
pathway. o The enzyme pyruvate kinase is inhibited by high
ATP concentrations also. So when there is high ATP
 While for fructose, for fructose it involves the
concentration, this will also signal the pyruvate
phosphorylation by ATP to produce fructose 1—
kinase enzymes to temporarily stop their function.
phosphate. So this fructose 1-phosphate it will then be
split into two trioses, namely glyceraldehyde and  So these are some of the ways that our body naturally
dihydroxyacetone phosphate. regulates the glycolytic pathway.
 So the dihydroxyacetone phosphate from fructose 1-6
phosphate it can already enter the glycolytic pathway and FATES OF PYRUVATE
undergo step 5 to allow the conversion of  What happens to the pyruvate molecules that were
dihydroxyacetone phosphate into glyceraldehyde 3- produced during the laast step of the glycolytic pathway.
phosphate.  So for the fates of pyruvate, it depends on the need of the
 While for the other trials produced from the cleavage of cell. Depends on the cell environment is the cell in an
the fructose 1-phosphate glyceraldehyde, for aerobic or anaerobic environment. So these are some of
glyceraldehyde this has to be phosphorylated first by the factors that may dictate what will happen to the
ATP, for it to become glyceraldehyde 3-phosphate. Once pyruvate molecules.
glyceraldehyde became or was converted into  Pyruvate it can be converted into acetyl coenzyme A and
glyceraldehyde 3-phosphate already, it can proceed up to if the reaction happened in an aerobic environment. But it
step 10 of glycolytic pathway. can also be converted into lactate and ethanol ifg the
reaction happens in anaerobic environment.

OXIDATION OF ACETYL COA


 This reaction happens in an aerobic environment where
in pyruvate is oxidized to form acetyl co enzyme A. So
this one it only happens when there is abundant oxygen
in the cell environment so pyruvate proceeds to the
mitochondrial matrix where oxidation will occur.
 So in this reaction both oxidation and decarboxylation,
when we say decarboxylation the end product is carbon
dioxide. So it involves oxidation and decarboxylation and
requires coenzymes such as NAD, Coenzyme A – SH,
FAD and 2 other coenzymes namely lipoic acid and
thiamin pyrophosphate
 So what happens in the reaction is that the carboxylate
ion of pyruvate is removed and this becomes the carbon
dioxide in the products side. The coenzyme A will attach
to whattt is now an acetyl group after removing the
carboxylate giving an end product of acetyl coenzyme A.
 Lastly, NAD was used as an oxidizing agent and this was
reduced into NADH.
REGULATION OF GLYCOLYSIS
 Similar to the other metabolic pathways, glycolysis has to
be controlled in order to maintain homeostasis or
balance. Some of these mechanisms are actually within
the pathway specifically steps 1, 3 and 10.
 Step 1:
o Conversion of glucose to glucose 6-phosphate by the
enzyme hexokinase. This step is inhibited nu glucose
6-phosphate.

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LACTATE FERMENTATION o Glycogenesis – excess glucose 6-phosphate is


 When fermentation is involved, NADH is oxidized to NAD converted into glycogen
o Glycogenolysis – breakdown of glycogen into
without the need for oxygen. So lactate fermentation
involves anaerobic reduction of pyruvate to lactate. So glucose-6 phosphate
meaning, there is no oxygen required for this process to o Gluconeogenesis – formation of glucose from non-
occur. carbohydrate sources.
 The main purpose of this process is for the conversion of
NADH to NAD because we want to restock, we want to TABLE: ATP PRODUCTION FOR THE COMPLETE
replenish the NAD supplies of our cells. However, when OXIDATION OF GLUCOSE
oxygen is present in the cellular environment, the lactate
is converted back to pyruvate.
 By looking at the chemical reaction, the oxygen that NAD
gained came from the carbonyl group of the pyruvate
molecule. Thatt is why NAD H is converted into NAD.
 While to compensate for the lloss of oxygen, a pyruvate
was converted into lactate.

ETHANOL FERMENTATION
 Next type of fermentation process is ethanol
fermentation, this occurs in an anaerobic environment
and organisms. For example, the yyeast which posses
the ability to regenerate NAD through ethanol. So the  This table shows the ATP production for the complete
enzymatic anaerobic conversion of pyruvate to ethanol oxidation of glucose.
and carbon dioxide  The following reactions are glycolysis, oxidation or
 In ethanol fermentation, there are two steps: pyruvate, citric acid cycle or krebs cycle and the ETC and
o For step 1, conversion of pyruvate to ethanol or there Oxidative phosphorylation.
is a decarboxylation process that occur to produce  So for the following we produce:
acetaldehyde. o Glycolysis – total of 4 ATP
o By looking at the reaction, the carboxylate ion of o Oxidation of pyruvate – NADH
pyruvate will be the carbon dioxide then the displaced o Citric acid cycle – 2 ATP
carboxyl is replaced by the hydrogen ion giving us an  Note: GTP is almost similar with ATP, GTP
acetaldehyde molecule. The enzyme needed for this stands for Guanosine Triphosphate.
reaction to occur is pyruvate decarboxylase. (Note: o Electron Transport Chain and Oxidative
Decarboxylase because it removed the carboxyl Phosphorylation – a total of 26 ATP.
group of pyruvate which became the carbon dioxide.  The total of ATP in this reaction is 32 but the
o So the hydrogen in the reactant side, it bonded with net production of your ATP is only 30 That’s
the remnant of the pyruvate to give acetaldehyde because we consume 2 ATP in the first 2 steps
molecule. of glycolysis so we minus 2 from 32 that’s why
you only have 30 ATP.

GLYCOGEN
 Glycogen is a stored form of carbohydrates in humans
o In Step 2, acetaldehyde was reduced therefore there and animals. This is a branch polymeric form of glucose.
is a removal of oxygen from its carbonyl group. So When polymeric, it means that this is a repeating unit of
this oxygen from the carbonyl group of the monomers so in glycogen, our monomer is glucose.
acetaldehyde molecule was donated to the NADH Therefore, glycogen is a repeating unit of glucose.
molecule, giving an oxidized NAD molecule. The Glycogen is primarily found In liver and muscle tissue.
enzyme required for this reaction is alcohol
dehydrogenase. FUNCTIONS OF GLYCOGEN
 Glycogen can be found in muscles and in liver. In the liver
when the body is hypoglycemic or when the person has
low blood glucose level, your glycogen is converted into
glucose. This glucose will enter the blood stream
increasing the blood glucose level.
 Next is in the muscle, your glycogen will be broken down
into glucose so that it can be a source of energy for the
 End product: Ethanol and NAD muscle cells.

CARBOHYDRATE METABOLISM GLYCOGENESIS


 Terminologies:  Glycogenesis is the synthesis of glycogen from glucose-
o -Lysis means breakdown 6-phosphate, so remember that glucose 6 phosphate or
o -Genesis means making G6P is the first metabolite from your glycolysis and the
o Glycolysis – glucose is converted into two excess G6P will be converted into glycogen.
molecules of pyruvate  Glycogenesis requires two ATP molecules and we have
three steps in glycogenesis which are:

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1. Isomerization – formation of glucose 1-phosphate the UDP-glucose. It will bring the glucose to its
2. Activation – Formation of UDP-Glucose destination which is the end chain of the glycogen. So
3. Linkage - Glucose transfer to a glycogen what will happen is that the glucose will be added to the
endd chain of the glycogen with the help of the enzyme
STEPS IN GLYVOGENESIS glycogen synthase.
 After this, the UDP will be converted back into UTP and
ISOMERIZATION then it will interact with another glucose 1-phosphate and
then this reaction will occur all over again until we can
 Glucose 6-phosphate will be converted into glucose 1-
form a branched glycogen.
phoshpate with the help of the enzyme
phosphoglucomutase.
 The phosphoglucomutase works in a way that the
phosphate group from the glucose 6-phosphate which is
attached on the six carbon of our glucose will be moved
to the first carbon of our glucose that’s why we have an
end product of: glucose 1-phosphate. Take note that
this reaction is reversible

GLYCOGENOLYSIS
 In glycogenolysis we are trying to breakdown glycogen so
that we can synthesize glucose-6-phosphate but then this
is not a reverse of glycogenesis because we do not need
or require an activator just like your UTP for this reaction
to occur.
ACTIVATION  There are two steps in glycogenolysis:
 In this reaction we’ll start with the end product of the first 1. Phosphorolysis – Formation of glucosee 1-
step which is the glucose 1-phosphate. In this reaction we phosphate
need an activator which is the Uridine Triphosphate and 2. Isomerization – Converting or formation of glucose
from the uridine triphosphate we will add uridine 1-phosphate to glucose 6-phosphate
monophosphate to our glucose 1-phosphate with the help
of the enzyme UDP-glucose pyrophosphorylase. PHOSPHOROLYSIS
 Endd product: uridine diphosphate glucose and two  Let’s have a quick review about the structure of glycogen:
inorganic phosphates. o Glycogen is a branch polymer of glucose, the linear
 These two inorganic phosphate came from the process chain is connected through the alpha 1,4- linkage
that: we added URIDINE MONOPHOSPHATE to glucose while the branch chain is connected through the
1-phosphate, and the two left phosphate is the two alpha-1,6- linkage. So our goal is to get a glucosee
inorganic phosphate. unit in the chain. The one enzyme responsible for
this is the glycogen phosphorylase.
o The glycogen phosphorylase will cut the alpha 1,4
linkage. However, the one responsible for cutting
the alpha 1,6 linkage is the debranching enzyme.
After this was cut, this chain will be a linear chain.
So we already got a glucose unitt. This phosphate
group will be added to our glucose unit, glucose-1-
phosphate and our endd product for this step is the
glucose 1-phosphate and the glycogen minus 1
glucose residue (n-1 residues)

LINKAGE TO CHAIN
 The final step of glycogenesis is linkage to chain, where
in we start with the end product of second step which is
the UDP-glucose. This UDP-glucose is the active carrier
of your glucose. Let’s think about it like the UDP-Glucose
is like a jeepney and then the glucose is the passenger of

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ISOMERIZATION enter blood stream which increases the glucose level ao


 In here, we are converting your glucose 1-phosphate into that it can go back to normal.
glucose-6-phosphate with the help of the enzyme  Let's now compare or let's now see the difference
phosphoglucomutase. between glycogenesis and glycogenolysis.
 The end product of glycogenolysis is glucose 6-  let's start with glycogenesis again in glycogenesis we
phosphate. Remember, your glycogen is stored in start with glucose 6-phosphate.
muscle, so in muscle the stimulus for glycogenolysis is  Your glucose 6-phosphate is the first metabolite of your
when the body is in need of energy or there is a low level glycolysis.
of energy. So once the body detects thatb we are in need  Glucose 6-phosphate will be converted into glucose 1-
of the energy, your glycogen is broken down into glucose phosphate with the help of the enzyme
6-phosphate which may undergo glycolysis producing phosphoglucomutase.
your pyruvate.  Glucose 6-phosphate will be converted into UDP glucose
 Another storage of your glycogen is the liver, so the with the help of enzyme UDP glucose phosphorylase and
stimulus for glycogenolysis in the liver is the low amount the activator.
of blood glucose level. Your glycogen is broken down into  UDP glucose is the active carrier of glucose. UDO
glucose 6-phosphate but your glucose 6-phosphate Glucose will attach this glucose to the end chain of your
cannot enter the bloodstream it needs to be converted glycogen with the help of the enzyme glycogen synthase
into three glucose so the enzyme responsible for and that’s the process of glycogenesis
converting glucose 6-phosphate into three glucose is your  Glycogenolysis, again we start with glycogen so what
glucose 6-phosphatase. This enzyme is specific for your we're trying to do is to remove one glucose unit from our
liver so you cant see it in your muscle and brain cells. So chain so we need the help of the enzyme glycogen
once we have your free glucose it can now enter the blood phosphorylase.
stream increasing the blood sugar.  Our end product for the first step is the glucose 1-
SUMMARY OF GLYCOGENESIS phosphate. Your glucose one phosphate will be
converted back into glucose 6-phosphate and then your
PHOSPHOROLYSIS glucose 6-phosphate may undergo glycolysis when the
body needs it okay. It uses body to perform our daily task.
 wherein we are trying to remove a glucose unit from our
glycogen chain with the enzyme glycogen phosphorylase. GLUCONEOGENESIS
 Our end product in this step is the glucose one phosphate
and the glycogen with one less glucose residue.  Gluco means Glucose, Neo means New, Genesis means
start off. In gluconeogenesis we are forming glucose from
non-carbohydrate sources
 This is the process where glucose can also be
synthesized from non – carbohydrate materials such
as Lactate, Glycerol and Certain amino acids.
 Ninety percent (90%) of this metabolic pathway takes
place in the liver which helps maintain normal blood –
glucose levels. ATP and GTP molecules are needed to
drive the process where Oxaloacetate is an intermediate
in this pathway.
 Formation of glucose from non-carbohydrate sources.
 LOCATION:
ISOMERIZATION o Liver (mostly) & kidney.
 WHY DOES GLUCONEOGENESIS OCCUR WHEN WE
 Glucose 1-phosphate was converted into glucose 6- HAVE GLYCOLYSIS AND GLYCOGENOLYSIS?
phosphate with the help of the enzyme o We have your glycogen as the stored form of glucose
phosphoglucomutase. but your glycogen stores in muscles and liver.
o Glycogen stores in muscle & liver are depleted within
12-18 hours of fasting. People who do intermittent
fasting (more than 16 hours of fasting) happens to
occur depletion of glycogen in their body, that’s
where gluconeogenesis occurs.
o It meets the body’s need for glucose when there is
insufficient carbohydrate from diet or glycogen
reserves.
WHY IS GLYCOGENOLYSIS IMPORTANT  A supply of glucose is necessary for the nervous system.
the brain is dependent on glucose so what are the non-
 For example, when you wake up in the morning and you carbohydrate sources for gluconeogenesis.
have an exam on biochem or cph you do not have the
time to eat breakfast. Instead of eating your breakfast
you’ll just study along so you can get higher score, that’s
when your glycogen will be used or will be converted into
glucose it will be or it will supply our brain and it can also
be used by our muscles that's because of glucose.

GLYCOGEN

 Glycogen in the liver when the person is hypoglycemic or


low-level glucose, the glycogen in the liver will be
converted into glucose or free glucose. This glucose will
OVERVIEW OF GLYCOLYSIS

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 The circles represent the number of carbons. We have


carbons so we have your g6p which will be converted into
f6p and then we have the f1 6b which will be converted
into two we have your glyceraldehyde 3-phosphate and
also your dihydroxyacetone phosphate. Your dhap will be
converted into ga3p so that they may undergo glycolysis.

 Next is we have your 1 3bpMAGg which will be converted


into 3pg and then we have the 2pg and second to the last  Your oaa or your oxaloacetate can now be converted into
step which is your pep or your phosphoenolpyruvate pep but as you can see your pep is only a three-carbon
which will be converted into pyruvates so the end product compound while your oxaloacetate has four carbons so
for your glycolysis are these two pyruvates. This is where we need to remove one carbon atom and add a
your gluconeogenesis starts. phosphate group because your pep has a phosphate in
its structure. The enzyme that will catalyze this reaction is
your phosphoenolpyruvate carboxy kinase. The
phosphate group will be coming from our gtp so our end
product for this reaction is your pep or your
phosphoenolpyruvate, your carbon dioxide which we
drive out from our oxaloacetate and the gtp where our
phosphate group came from your pep will now undergo
the reverse process of glycolysis.
 but when it is already in the fructose 1 6 bisphosphate this
cannot be converted directly, we need an enzyme that will
catalyze this reaction. So, the enzyme that will help in this
reaction is the fructose 1-6 bis phosphatase this enzyme
will convert your f16bp into f6p or your fructose
 But notice that this step is irreversible that's why we need
phosphate. We do not need your ATP because we
an additional enzyme which may catalyze this reaction
remove a phosphate group from your f16bp.
also in glycolysis there are 11 compounds involved in this
process but in gluconeogenesis we have 12.

 Your f6p will be converted into g6p. Your g6p or your


glucose 6-phosphate will now be converted into glucose
 Again, in gluconeogenesis we start with the last step of with the help of the enzyme glucose 6 phosphatase again
glycolysis so we have our pyruvates remember your no ATP is required in this reaction so that is our
pyruvate cannot be directly converted into pep that's why gluconeogenesis.
we need an enzyme that will catalyze this reaction your
pyruvate is first converted into oxaloacetate as you can
see your oxaloacetate is a four-carbon compound while
your pyruvate is only three or has only three carbons.

HOW DOES GLUCONEOGENESIS HAPPEN?

 Gluconeogenesis starts with the last step of


 So, we need to add a carbon atom into our pyruvate the glycolysis which is the conversion of pep or your
enzyme that will catalyze this reaction is your pyruvate phosphoenolpyruvate into pyruvate.
carboxylase with the help of its cofactor biotin we also  That's why you can also say that gluconeogenesis is the
need your ATP and water so the end product on this reverse of glycolysis but there are steps in glycolysis
reaction is your oxaloacetate, ADP and the inorganic which are reversible.
phosphate.

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 This is the side-by-side comparison of your glycolysis and


gluconeogenesis.

AMINO ACID
 Protein catabolism will produce your amino acids your
amino acids will be converted into pyruvate and then it will
go or it will undergo gluconeogenesis.

 There are process which are not reversible. This are:


o The conversion of glucose into g6p and the
conversion of f6p into f1-6bp and also the conversion
of pep or your phosphoenolpyruvate into pyruvate.
o So, this is the last step of glycolysis. The last step of
glycolysis is the first step of gluconeogenesis before
your pyruvate can be converted into pep. we need to
convert your pyruvate into oxaloacetate first with the
help of the enzyme pyruvate carboxylase. Once we
have our oaa this can now be converted into pep so
we need the help of the enzyme
phosphoenolpyruvate carboxykinase and we also GLYCEROL
need your gtp since we are adding a phosphate
group to our oaa.  glycerol will be converted into glycerol 3-phosphate
o We now have your pep which will undergo like the and then it can now be converted.
reverse steps of glycolysis so once it reaches your
f1-6pp this molecule or this compound cannot be
directly converted into f6p so we need an enzyme
which will catalyze this reaction so the enzyme is
your f16bp so once it is converted into fructose 6-
phosphate it can now be converted it into glucose 6-
phosphate your g6p will be converted into glucose
with the help of the enzyme glucose phosphatase
where no ATP is required. So again, the last step of
glycolysis is the start of your gluconeogenesis so
from pyruvate where the oxaloacetate and then into
your pep.
o CORI CYCLE
 Gluconeogenesis and glycolysis are not exact opposites.
 12 compounds are involved in gluconeogenesis and only  One of the cyclic metabolic pathways associated with
11 in glycolysis because of the presence of oxaloacetate. gluconeogenesis.
 The last step of glycolysis is the first step of  Process in which glucose is converted to lactate in
gluconeogenesis. muscle tissue. The lactate is reconverted to glucose into
the liver and the glucose is returned to the muscle
NON-CARBOHYDRATE SOURCES OF  The lactate produced during strenuous exercise diffuses
GLUCONEOGENESIS from muscle into the blood, where it is transported to the
liver.
o So when we exercise we produce lactate again your
LACTATE
lactate is from your pyruvate which is produced from
 is produced in your muscles so when we exercise your glycolysis this lactate will be diffused from your
glucose or your glycogen is converted in will undergo muscle and into the blood then it will go in your liver.
glycolysis the end product glycolysis is your pyruvate your  Enzyme Lactate dehydrogenase converts lactate back to
pyruvate is then converted into lactate with the enzyme pyruvate.
lactate dehydrogenase. So, your lactate will diffuse
from your muscle into the bloodstream and then into
your liver so in liver your lactate is converted back into
pyruvate with the same and with the same enzyme lactate
dehydrogenase and then it will undergo gluconeogenesis.

 So, when we exercise, we use glucose and it will undergo


glycolysis to produce pyruvate. Your pyruvate is then
converted into lactate, this lactate will diffuse from your

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MODULE 7: CARBOHYDRATE, PROTEIN & LIPID METABOLISM

muscle into the blood and then it will go into the liver your o Your NADPH is a reducing agent and it is also
lactate will be converted back into pyruvate with the important in fatty acid synthesis, your
enzyme lactate dehydrogenase and then your pyruvate cholesterol metabolism and also nucleotide
will now undergo gluconeogenesis producing your synthesis.
glucose. According to Cori Cycle, this glucose produce
will go back into the muscle so that it can be used or it
can undergo glycolysis so that it will produce your
pyruvate which can be used up by the body.

 The net equation for the oxidative stage of the pentose


phosphate pathway is:

PENTOSE PHOSPHATE PATHWAY  So, we needed 2 NADP to convert your glucose 6-


phosphate into ribulose 5-phosphate. We also
 Aside from glycolysis, Pentose Phosphate pathway also produced your carbon dioxide your 2 NADPH and the
degrades glucose. two hydrogens.
 Glucose is degraded to produce:
o Synthesis of the coenzyme NADPH needed in lipid 2. NON-OXIDATIVE STAGE
biosynthesis.
o Production of ribose 5-phosphate needed for the
 Ribulose 5-phosphate (a ketose) is isomerized to ribose
synthesis of nucleic acids and many coenzymes
5-phosphate (an aldose).
 In pentose phosphate pathway we use glucose to
 Ribulose 5-phosphate will be isomerized into ribose
synthesize the coenzyme NADPH needed in lipid
5-phosphate with the enzyme phosphopentose
biosynthesis and also we use it to produce your ribose 5-
isomerase so from ketose we have an aldose so again
phosphate which is important in the synthesis of nucleic
the end product of your non-oxidative stage is your ribose
acids and many coenzymes.
5-phosphate so your ribose is a pentose which is an
important component of your ATP, GTP, UTP and also
TWO STAGES OF PPP these coenzymes and of course your RNA which we
talked about in module five
1. OXIDATIVE STAGE

 Occurs first
 Conversion of glucose 6-phosphate to ribulose 5-
phosphate.

o This is the more detailed discussion of your oxidative  The pentose ribose is a component of: ATP, GTP, UTP,
stage. So we start with your glucose 6-phosphate. CoA, NAD+/NADH, FAD/FADH2, & RNA
o g6p will be oxidized into 6-phosphogluctone that's  Further steps in the nonoxidative stage will convert
why we need your coenzyme. So in this reaction our ribose 5-phosphate to other sugar phosphates.
coenzyme is your NADP which will be reduced into  Glyceraldehyde 3-phosphate and fructose 6-phosphate
NADPH and the enzyme that will help this reaction is are formed which will undergo glycolysis.
your glucose 6-phosphate dehydrogenase and then
your 6-phospho-gluconolactone will be converted
into 6-phosphogluconate with the help of the enzyme
6-phospho-glucono lactase (glucono lactonase idk
bakit binanggit ni mam yan bigla T—T di aq sure if
kasama siya or yun dapat yung enzyme).
o Your 6-phosphate gluconate will be oxidized into  Ribose 5-phosphate is converted into ribose 5-phosphate
ribulose 5-phosphate that's why with the help of the enzyme phosphopentose isomerase
we need the NADP again as our coenzyme the and then further steps in this stage or in the non-oxidative
enzyme that will help this reaction is your stage your ribose 5-phosphate may lose two carbons
phosphogluconate dehydrogenase so the important which will produce your glyceraldehyde 3-phosphate
products of this stage is your NADPH which may undergo glycolysis or it can be or it may gain
three carbons and it will be converted into f6p which can
undergo glycolysis.

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MODULE 7: CARBOHYDRATE, PROTEIN & LIPID METABOLISM

FUNCTIONS OF PENTOSE PHOSPHATE PATHWAY 


AND ITS INTERMEDIATES
3. EPINEPHRINE
1. When ATP demand is high, the pathway continues to its
end products, which enter glycolysis  Also called adrenaline.
2. When NADPH demand is high, intermediates are recycled  Released by adrenal glands in response to anger, fear, or
to glucose 6-phosphate, & further NADPH is produced. excitement.
3. When ribose 5-phosphate is high, for nucleic acid and  Similar function with glucagon. It will send signal so
coenzyme production, most nonoxidative stage is that glycogen can be converted into glucose to increase
nonfunctional, leaving ribose 5-phosphate as a major product. blood glucose.
 Stimulation of glycogenolysis
HORMONAL CONTROL OF CARBOHYDRATE
METABOLISM

1. INSULIN

 Released by the beta cells of the islet of Langerhans


in the pancreas which promotes uptake and utilization of
glucose by cells.
 Main function: Insulin lowers blood glucose levels
because it promotes uptake and utilization of glucose by
cells
 Release of this hormone is triggered by high – blood
glucose levels in the circulation.
 Mechanism of action involves the bonding of the hormone
to the protein receptors on the outer surface of the cell, B VITAMINS AND CARBOHYDRATE METABOLISM
which facilitates the entry of glucose into the cell. This
hormone also increases rates of glycogenesis, glycolysis B VITAMINS
and fatty acid synthesis.  Involved in carbohydrate metabolism such as
o Diabetic people are dependent from insulin injection glycolysis, gluconeogenesis, glycogenesis,
to lower their blood glucose levels because in glycogenolysis, & conversion of pyruvate to acetyl CoA
diabetes, your receptor have problem so they cannot and Lactate.
enter the glucose into the cell that’s why they need
insulin. WHAT ARE THESE B VITAMINS?

 NIACIN (NAD+, NADH)


 RIBOFLAVIN (FAD)
 THIAMIN (TPP)
 PANTOTHENIC ACID (CoA)

TWO NEWLY INVOLVED B VITAMINS

 BIOTIN
o Biotin involvement occurs in the enzyme pyruvate
2. GLUCAGON carboxylase.
 Involves in the conversion of pyruvate into oxaloacetate
 Hormone released by the alpha cells of the islet of so that step is in the gluconeogenesis
Langerhans in the pancreas.
o Glucagon increases your blood glucose  Vitamin B6
concentration by speeding up the conversion of your o Vitamin B6 in the form of PLP in glycogenosis
glycogen to glucose and gluconeogenesis.
o Produced in pancreas by the alpha cells.
 Glucagon is released when blood – glucose levels are
low thus function by increasing the blood glucose
concentration by speeding up the conversion of glycogen
to glucose and gluconeogenesis in the liver.

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MODULE 7: CARBOHYDRATE, PROTEIN & LIPID METABOLISM

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MODULE 7: CARBOHYDRATE, PROTEIN & LIPID METABOLISM

CASTRO AL, BSMT-1-B, BERNARDO VG, BSMT1F, BONIFACIO RF BSMT1 E 15


MTChem2:Biochemistry for MLS
Module 7: (Lecture)
Lipid and Protein Metabolism College A.Y. 2021 – 2022 – 2

o Pancreas acts as both exocrine gland, which can


OUTLINE release enzyme lipase that hydrolyze fat globules
I Lipid Metabolism and endocrine gland.
A Digestion and Absorption of Lipid • After the hydrolyzation of our fat globules, we will have
B Hydrolysis of TAG the products of hydrolysis: Free fatty acids and
C Glycerol Metabolism monoacylglycerol/glycerol (complete and incomplete
D Fatty Acid Catabolism by Beta-Oxidation
hydrolysis)
II Protein Metabolism
A Amino Acid Catabolism • Bile will help the hydrolyzed products to combine into
B Carbon Skeleton Catabolism spherical droplets called micelle
• Micelle will go to the intestinal wall
LIPID METABOLISM • Free fatty acids and monoacylglycerol goes back to TAG
• Mainly focusing on triacylglycerol (TAG) • TAG combines with membrane lipids (phospholipid and
• Molecules of triacylglycerol (TAG) are the main focal point cholesterol – which are partly protein and partly lipid) and
of lipid metabolism water-soluble proteins
• TAG is hydrolyzed with the assistance of the enzyme • Chylomicron is formed for the transport of triglyceride to
lipase our bloodstream
• In the whole lipid metabolism, we would always encounter o It has the highest in triglyceride content out of all
the hydrolysis reaction to breakdown the triacylglycerol the four lipoproteins namely:
(TAG) → the product of hydrolysis will gather together for → Chylomicron – for transport
it to become TAG again → TAG will destroy the hydrolysis → Very low-density lipoproteins (VLDL) –
→ and so on and so forth. for transport
→ Low-density lipoproteins (LDL)
2 TYPES OF HYDROLYSIS (TAG) → High-density lipoproteins (HDL)
COMPLETE HYDROLYSIS o It has three contents:
→ TAG
• 3 free fatty acids are removed + glycerol
→ Phospholipid
INCOMPLETE HYDROLYSIS → Cholesterol
• 2 free fatty acids are removed + monoacylglycerol

DIGESTION AND ABSORPTION OF LIPID


• The major site of Lipid catabolism happ ens in the
stomach:

Metaboli Metabolic Metabolite


sm type agent/process
Major Physical Churning Chyme
change Change (movement) of (TAG
(90% of the stomach globules) –
TAG) fat globules • Chylomicron will enter the bloodstream via the lymphatic
Minor Chemical Hydrolysis by Free fatty system
change Change gastric lipase – acids and o lymph fluid are colored milky (chylous) because
(10% of the 1st enzyme glycerol it is rich in chylomicrons
TAG) that conducts (complete • TAG is released from the chylomicron upon reaching the
hydrolysis on hydrolysis) target tissue
lipids or • Again, we have 3 lipases involved in the metabolism of
monoacylg lipids: gastric lipase, pancreatic lipase, and
lycerol lipoprotein lipase
(incomplete • Lipoprotein lipases will hydrolyze TAG into free fatty
hydrolysis) acids and glycerol – this will be the last time that we will
hydrolyze the triacyglycerides
Note: Whenever there’s a reaction of churning of stomach, it • Some products of hydrolysis will be broken down into
is not only the lipids that is being breakdown, it also include acetylCoA for energy
carbohydrates, proteins, etc; undigested foods + hydrochloric • Some products of hydrolysis will go back as TAG to be
acid (HCl) or the stomach acid = chyme (TAG globules). stored
For major change: o If these products really go back as TAG, this will
• Chyme triggers small intestine to release the hormone now be our “adipose tissues”
cholecystokinin
o this hormones triggers our gallbladder since it has
tissue receptors that will release bile
• Gallbladder releases bile
• Bile emulsifies TAG globules
o fat globules are immiscible/insoluble
o if there’s an emulsification, it makes the immiscible
products miscible so it will be easy to hydrolyze -
this tends to free the fatty acids and glycerols and
thus, large molecules are now easier to transport.
• Soluble TAG globules are hydrolyzed by pancreatic
lipases

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MODULE 7: LIPID AND PROTEIN METABOLISM

FLOW CHART OF LIPID METABOLISM to oxidize first through NAD+ which will act as an oxidizing
agent.
• After the oxidation process, we will have the
dihydroxyacetone phosphate; ATP will become ADP
(energy) and NAD+ will become NADH (reduced form)
plus the hydrogen proton (H+)

FATTY ACID CATABOLISM BY BETA-OXIDATION

STEP PRODUCT FORMED


Oxidation Trans-Enoyl CoA
HYDROLYSIS OF TAG Hydration L-Beta-Hydroxyacyl CoA
• For complete hydrolysis, triglycerides (fats) can be Oxidation Beta-Ketoacyl CoA
hydrolyzed to produce glycerol and 3 free fatty acids in Chain Cleavage Acetyl CoA
the presence of water (3H2O).
STEP 1: OXIDATION (DEHYDROGENATION)
• Hydrogen atoms are removed from the alpha and beta
carbons, creating a double bond between these two
carbon atoms. FAD is the oxidizing agent, and a FADH2
molecule is a product.

• For incomplete hydrolysis, triacyglycerol can be


hydrolyzed to produce monoacylglycerol and 2 free
fatty acids in the presence of water (2H2O).
• The enzyme involved is stereospecific in that only trans
double bonds are produced.

STEP 2: HYDRATION
• A molecule of water is added across the trans double
bond, producing a secondary alcohol at the beta-carbon
position. Again, the enzyme involved is stereospecific in
that only the L-hydroxy isomer is produced from the
trans double bond.
GLYCEROL METABOLISM
• The glycerol enters the bloodstream and is converted to
glycerol 3-phosphate by the enzyme glycerol kinase,
and the resulting glycerol 3-phosphate is oxidized to
dihydroxyacetone phosphate by the enzyme glycerol-
3-phosphate dehydrogenase.
• The glycolytic enzyme triose phosphate • The enzyme involved in this hydration will also hydrate a
isomerase converts dihydroxyacetone phosphate cis double bond, but the product then is the D isomer.
to glyceraldehyde 3-phosphate, which is oxidized We shall return to this point later in considering how
via glycolysis, or converted to glucose unsaturated fatty acids are oxidized.
via gluconeogenesis.
STEP 3: OXIDATION (DEHYDROGENATION)
• The Beta-hydroxy group is oxidized to a ketone
functional group with NAD+ serving as the oxidizing
agent. The required enzyme exhibits absolute
stereospecificity for the L isomer.

Simplified Chemical Reaction that Involves Glycerol


• It is now apparent why the name for this series of
reactions is B-oxidation pathway. The Beta-carbon atom
has been oxidized from a –CH2–group to a ketone group.
• Glycerol will react with our ATP and NAD+.
• Always remember that the job the ATP in this reaction is
that it wants to become ADP – it wants to release a
phosphate molecule. Before ATP can do that, it will need

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MODULE 7: LIPID AND PROTEIN METABOLISM

CHAIN CLEAVAGE AMINO ACID CATABOLISM


• The fatty acid chain is broken between the alpha and TRANSAMINATION REACTION
beta carbons by reaction with a coenzyme A molecule. • Biochemical reaction that involves the interchange of
The result is an acetyl CoA molecule and a new acy1 CA amino group of alpha amino acid with keto group of an
molecule that is shorter by two carbon atoms than its alpha keto group
predecessor.

• In here, the alpha-amino acid gives its NH3 to the alpha-


• The new acyl CoA molecule (now shorter by two carbons) keto acid which in turn, gives its oxygen to alpha-amino
is recycled through the same set of four reactions again. acid.
This yields another acetyl CoA, a two-carbon-shorter • The difference of this to deamination is that, in this
new acyl CoA, FADH2, and NADH. Recycling occurs phase, we will totally remove the NH3. We have to
again and again, until the entire fatty acid is converted to remove this ammonia because of the urea cycle.
acetyl CoA. Thus the fatty acid carbon chain is
sequentially degraded, two carbons at a time. UREA CYCLE
• This will be the product of our transamination and
PROTEIN METABOLISM: AMINO ACIDS deamination phase.
• Series of biochemical reactions in which urea is produced
FLOW CHART OF PROTEIN METABOLISM from ammonium ions and carbon dioxide.
• Our main purpose here is to free the amino acids. • Also produces energy.

• We have here the NH4+ that will react with CO2 and 3
molecules of ATP with water and aspartate.
• As mentioned, the job of ATP is that it wants oxidize first
to release one phosphate molecule and become ADP for
energy.
• After the reaction, we will be having urea (waste product)
o It is released by our urine
o There will be a problem in our blood (blood urea
nitrogen) if we don’t release this urea.
• Free amino acids will go to the liver to be synthesized as • The energy that will be produced from our urea cycle are
different proteins that makes up the body the 2 molecules of ADP and 1 molecule of AMP.
• Excess amino acids will be used as energy source:
o Glucogenic amino acids – will stick to carbohydrate
metabolism
o Ketogenic amino acids – will stick to lipid
metabolism
o Deamination/Transamination – comes in urea
cycle wherein there will be a formation of nitrogen,
which in turn will be ammonia.
• The majority of our amino acids after degradation can be
differentiated into two major portions:
o Carbon Portion
→ Triacylglycerols via fatty acids
→ Glucose via gluconeogenesis
→ ATP via citric acid cycle
→ Ketone bodies via ketogenesis
o Nitrogen Portion
→ Elimination via urea
→ Biosynthesis of nonessential amino acids CARBON SKELETON CATABOLISM
→ Biosynthesis of nonprotein nitrogen- • These are alpha keto acids that contains carbon skeleton
containing compounds from the amino acid.
• Different degradation for each of 20 amino acids

7 products of carbon skeleton catabolism:


→ Pyruvate
→ Acety| COA
→ Acetoacetyl CoA
→ Alpha-ketoglutarate
→ Succiny| CoA
→ Fumarate
→ Oxaloacetate

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MODULE 7: LIPID AND PROTEIN METABOLISM

• There are different types of amino acids, their process of


degradation, as well as their products.

• Under pyruvate, we have:


Alanine
Glycine
Cysteine
Serine
Threonine
Tryptophan

• Under Acetyl CoA, we have:


Isoleucine
Leucine
Tryptophan

• Under Acetoacetyl CoA, we have:


Leucine
Lysine
Tryptophan
Phenylalanine
Tyrosine
Tryptophan

• All of these (pyruvate, acetyl CoA, and acetoacetyl CoA


have the products called ketone bodies that stick to our
lipids.

• Other amino acids mentioned below have the product


alpha-ketoglutarate.
Glutamate
Glutamine
Histidine
Proline
Arginine

• Under Succinyl CoA, we have:


Isoleucine
Methionine
Valine

• Under Fumarate, we have:


Tyrosine
Phenylalanine
Aspartate

• Under Oxaloacetate, we have:


Asparagine
Aspartate

CASTRO, KATELYN – BSMT-1B 4

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