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Biochemistry Reviewer

I.

Carbohydrate Structure

Biomedical Importance of Carbohydrates:


1. Structural functional component of cell structures
2. Metabolic dietary carbohydrates mostly absorb is Glucose.
The liver converts other carbohydrates to Glucose
Glucose is a major source of energy (metabolic fuel) and the precursor in the synthesis of
all other CHO ex. Glycogen, Lactose and components of Glycolipids. Glycoproteins,
Proteoglycans
3. Diseases involving carbohydrate metabolism Diabetes mellitus, Galactosemia, Glycogen
Storage Diseases, Lactose intolerance
Structure of Carbohydrates
1. Simple
a. Monosaccharides ex. Six carbon sugars glucose, Galactose, Mannose
Classification based on number of carbons
Triose

3 carbons ex. Glyceraldehyde

Tetrose 4 carbons ex. Erythrose


Pentose 5 carbons ex. Ribose
Hexose 6 carbons ex. Glucose
Classification based on functional groups
Aldose Glycerose, Erythrose, Ribose, Glucose
Ketose dihydroxy acetone, Erythrulose, Ribulose, Fructose
b. Dissacharides sucrose, lactose, maltose
2. Complex
a. Oligossacharides condensation products of 3 10 monosaccharides.
b. Polyssacharides condensation products of more than 10 monossacharides. May be
linear or branched chains. Ex. Glycogen (storage form of glucose in animals):
mostly found in liver and muscle
same structure as amylopectin, but with more branches (11 units)
provides efficient storage of glucose and prevents high osmotic pressure in cells

one glycogen molecule may contain 1,000,000 glucose molecules but only counts as 1
particle for osmosis best way to store glucose without affecting significantly osmotic
intracellular properties
Hexosans polyssacharides made up of 6 carbon monossacharides
Pentosans polyssacharides made up of 5 carbon monossacharides
Isomers same structural formula different configuration (Glucose with 4 asymmetric carbons can
form 16 isomers
Epimers isomers differing as a result of variations in configuration of the OH and H atoms at only
one asymmetric carbon ex. Glucose and Galactose at the 4th carbon, Glucose and Mannose at
the 2nd carbon.
Enantiomers a pair of stereoisomers that are non-superimposable mirror images of each other
Asymmetric (chiral) carbon centers = must have a carbon atom connected to 4 different
atoms or groups of atoms bonded in a tetrahedral structure
Type of monosaccharide is based on alcohol (OH) group bonded to only or last asymmetric
carbon atom (adjacent to last alcohol carbon) D = right and L = left (mirror images)
Biomedical and clinical importance of monosaccharide:
1. Glyceraldehyde and dihydroxyacetone important intermediates in glycolysis; branching points
in metabolism
2. Ribose and 2-deoxyribose are important in RNA, DNA, and nucleotide (ATP) structures. Ribose in
RNA is synthesized via the Pentose Phosphate Pathway and the deoxyribose is produced from
ribonucleotide diphosphates by ribonucleotide reductase. Structural component of coenzymes,
including ATP, NAD(P), and flavin coenzymes.
3. Glucose (hexose or blood sugar) (D(+)) important in cellular energy production. Derangement in
the metabolism of glucose is the main issue in Diabetes mellitus.
4. Galactose (D(+) readily metabolized to Glucose. Precursor for the synthesis of lactose and
important in glycoproteins and lipids that are involved with nerve and brain function. Hereditary
galactosemia as a result of failure to metabolize galactose leads to cataracts
5. Fructose (laevulose or fruit sugar) is extremely sweet. Has fewer calories per gram than other
sugar. Hereditary fructose intolerance leads to fructose accumulation and hypoglycemia
Amino Sugars
D-glucosamine constituent of hyaluronic acid
D-galactosamine (Chondrosamine) constituent of chondroitin important component of the
extracellular matrix.

Acidic sugars
Oxidation will result to gain of oxygen and loss of Hydrogen (electrons) Oxidation of glucose (6th
carbon OH is oxidized COO- forming Glucoronic Acid). This is important in the
biosynthesis of GAG.
II.

Carbohydrate Metabolism
Glucose Metabolism

Metabolic Fates of Glucose


1.

Glycolysis and Citric Acid Cycle

2. Synthesis of glycogen for storage in animals


3. Synthesis of Ribose as important component for the synthesis of RNA
4. Conversion to other biological substances ex. Galactose for the synthesis of Lactose
5. Acidification as in Uronic acid pathway conversion of glucose to glucorunic acid important in
the biosynthesis of GAG

A. Glycolysis
-

occurs in the cytosol

major pathway for glucose metabolism

aerobic or anaerobic in aerobic metabolism, pyruvate is oxidized by pyruvate


dehydrogenase to produce acetyl CoA that enters the Krebs Cycle; in anaerobic,
pyruvate is reduced to lactate by lactate dehydrogenase and is shuttled to the liver for
gluconeogenesis.

end product is pyruvate

three regulatory steps are involved (rate limiting steps) catalyzed by the following
enzymes:
1). Hexokinase Phosphorylate Glucose intracellularly. (Hexokinase is
nonspecific with high affinity and low Km for glucose) Glucokinase is an isozyme of
hexokinase with low affinity and high Km for glucose found in the liver and pancreas.
Phosphorylation of glucose is irreversible.

allosterically inhibited by its product (Glucose-6-Phosphate)

2). Phosphofructokinase 1 Phosphorylate fructose-1-phosphate at C6 to


produce Fructose 1,6 bisphosphate. Reaction is irreversible under physiologic condition.
Has a major role in regulating glycolysis

Allosterically regulated by:


Fructose 2,6 bisphosphate (strong activator)
5AMP (activator)
ATP (inhibitor)

3). Pyruvate kinase transfers the phosphate of phosphoenolpyruvate to ADP


to form ATP. The reaction is irreversible under physiologic condition.
Cells (hepatocytes) capable of gluconeogenesis have different enzymes in the 3
regulatory steps to reverse glycolysis.

B. Tricarboxylic Acid Cycle (TCA, Citric Acid Cycle, Krebs Cycle)

Occurs in the mitochondria

Oxidize the acetate of acetyl CoA

Reduce the coenzymes NAD, FAD to be used as electron carriers to the Electron
Transport Chain for ATP synthesis. 3 NADH + H and 1 FADH2 are produced per turn of
the cycle. One ATP is produced by substrate level phosphorylation per turn of the cycle

Common final pathway for the oxidation of


o

glucose (acetyl CoA produced from the oxidation of the final product of
glycolysis which is Pyruvate),

fatty acids (acetyl CoA produced in beta oxidation) and

amino acids (acetyl CoA from pyruvate the degradation product of glucogenic
amino acids and acetyl CoA the degradation product of ketogenic amino acids).

It has central roles in Gluconeogenesis, Lipogenesis, Amino acid synthesis. It has


anaplerotic reactions it provides substrates for other reactions/pathways like
gluconeogenesis (Phosphoenolpyruvate decarboxylase forms Pyruvate from
decarboxylation of oxaloacetate). When concentration of acetyl CoA is high, it inhibits
Pyruvate dehydrogenase and activates Pyruvate carboxylase. Increase activity of
Pyruvate carboxylase increases the concentration of oxaloacetate.
o

Gluconeogenesis TCA cycle provides substrates for gluconeogenesis ex.


Oxaloacetate converted to Phosphenolpyruvate by Phosphoenolpyruvate
decarboxylase

Fatty acid synthesis acetyl CoA a substrate of TCA cycle is a precursor for fatty
acid synthesis. Pyruvate dehydrogenase is a mitochondrial enzyme thus acetyl
CoA is formed in the mitochondria. Fatty acid synthesis occurs in the cytosol so
the acetyl CoA formed in the mitochondria should be available in the cytosol.
Acetyl CoA is provided for fatty acid synthesis when citrate (a product produced
from the condensation of axaloacetate and acetyl CoA) is transported to the
cytosol. In the cytosol citrate is cleaved to acetyl CoA and Oxaloacetate by ATPcitrate lyase. Citrate is transported out of the inner mitochondrial membrane
when aconitase is saturated with acetyl CoA.

Amino acid synthesis -ketoglutarate a substrate of TCA cycle is a keto acid of


glutamate, oxaloacetate a ketoacid of aspartate. The ketoacid is converted to
an amino acid by transamination and back by deamination.

TCA has functions of both oxidative (degradative) and synthetic processes thus, it is
amphibolic.

Aconitase isomerizes citrate to isocitrate is inhibited by Fluoroacetate causing


accumulation of citrate.

-ketoglutarate dehydrogenase complex converts -ketoglurate to succinyl CoA. It has


the same cofactors with that of Pyruvate dehydrogenase which are thiamine
diphosphates, lipoate, NAD+, FAD, and CoA. It is inhibited by Arsenite causing
accumulation of -ketoglutarate.

The reaction catalyzed by succinate thiokinase (synthetase) is the only reaction in TCA
that has phosphate level phosphorylation. It has 2 isozymes in gluconeogenic and nongluconeogenic tissues:
o

Gluconeogenic tissues (liver and kidney) has to isozymes, one is specific with
GDP and the other is ADP. The GTP formed is used in the decarboxylation of
oxaloacetate (phosphoenolpyruvate carboxykinase) to phosphoenolpyruvate. It
provides a regulatory link between citric acid cycle activity and the withdrawal
of oxaloacetate for gluconeogenesis.

o
-

Non-gluconeogenic tissues the isozyme is specific for ADP

Malate dehydrogenase produces oxaloacetate and NADH from malate. Oxaloacetate is


consumed by:
o

Coupling with acetyl CoA to form citrate

Decarboxylation to form phosphoenolpyruvate

Transamination to aspartate

Ten ATPs are formed per turn of the cycle (3 NADH ~2.5 ATPs , 1 FADH2 ~ 1.5 ATPs, 1
ATP in substrate level phosphorylation)

Vitamins that play a role in TCA:


o

(1) riboflavin, in the form of flavin adenine dinucleotide (FAD), a cofactor for
succinate dehydrogenase;

(2) niacin, in the form of nicotinamide adenine dinucleotide (NAD), the electron
acceptor for isocitrate dehydrogenase, -ketoglutarate dehydrogenase, and
malate dehydrogenase;

(3) thiamin (vitamin B1), as thiamin diphosphates, the coenzyme for


decarboxylation in the -ketoglutarate dehydrogenase reaction; and

(4) pantothenic acid, as part of coenzyme A, the cofactor attached to "active"


carboxylic acid residues such as acetyl-CoA and succinyl-CoA.

Regulation of TCA is dependent on the:


o

availability of NAD that is dependent on the concentration of ADP (due to tight


coupling of oxidation and phosphorylation.

rate of utilization of ATP

enzymes of the cycle Sites of regulation are the nonequilibrium reactions


catalyzed by; Pyruvate dehydrogenase, citrate synthase, isocitrate
dehydrogenase, and -ketoglutarate dehydrogenase.

Dehydrogenases are activated by calcium Calcium concentration


increase during muscle contraction requiring energy

In the brain the control is in pyruvated dehydrogenase. The brain is


largely dependent glucose to supply acetyl CoA

Some enzymes are regulated by the energy status; [ATP]/[ADP] and


[NADH]/[NAD+] ratios

allosteric inhibition of citrate synthase by ATP and long-chain


fatty acyl-CoA

Allosteric activation of mitochondrial NAD-dependent isocitrate


dehydrogenase by ADP is counteracted by ATP and NADH

-ketoglutarate dehydrogenase complex is regulated in the same way as


is pyruvate dehydrogenase

Succinate dehydrogenase is inhibited by oxaloacetate, and the


availability of oxaloacetate, as controlled by malate dehydrogenase,
depends on the [NADH]/[NAD+] ratio

the Km for oxaloacetate of citrate synthase is of the same order of


magnitude as the intramitochondrial concentration, it is likely that the
concentration of oxaloacetate controls the rate of citrate formation

C. Glycogen metabolism
-

Glycogen is the major carbohydrate storage in man

Liver contains higher glycogen content by weight, however total glycogen is of the
total glycogen is in muscles (muscle mass is greater than that of the liver).
o

Liver (from glycogen or gluconeogenesis) exports glucose to maintain blood


glucose level, provides glucose for the other tissues of the body,

Muscle glycogen provides fuel for ATP synthesis. Muscle lacks glucose-6phosphatase so it cant produce glucose from glucose 6 phosphate a product of
the isomerization of Glucose-1-phosphate (G1P) from glycogenolysis.

1. Glycogenesis
- Occurs mainly in the liver and muscle
- One of the pathways in glucose metabolism that utilize glucose 6 phosphate (G6P). G6P
is isomerized to G1P by phosphoglucomutase the starting substrate for glycogenesis.
- Uridine diphosphates glucose phosphorylase catalyszes the reaction of G1P and uridine
triphosphate (UTP) to uridine diphosphate glucose (UDPGlc) the active nucleotide and
pyrophosphate.
- UDPGlc is the substrate of glycogen synthase which catalyzes the formation of a
glycoside bond between C-1 of the glucose of UDPGlc and C-4 of a terminal glucose
residue of glycogen. It is the source of glucose in the glycosylation of a tyrosine residue
of glycogenin.
o

In the muscle the glycogenin remains attached in the center of the glycogen
molecule

In the liver the number of glycogen molecules is more than the number of
glycogenin molecules

- Synthesis of glycogen requires a primer called glycogenin


- When an elongated chain of glucose reaches about 11 moieties, a branching enzyme
promotes the transfer of a part of the chain (at least 6 moieties of glucose) to a
neighboring chain to form a 1-6 linkage.
2. Glycogenolysis
-

Degradation of glycogen to yield G1P the isomerized to G6P (in the liver G6P is
dephosphorylated by glucose 6 phosphatase releasing glucose to the circulation; in
the muscle G6P is metabolized in glycolysis).

Glycogen phosphorylase catalyzes the the phosphoroylytic cleavage


(phosphorolysis; of hydrolysis) of the 1- 4 linkages of glycogen to yield glucose 1phosphate rate-limiting step in glycogenolysis

glucan transferase transfers a trisaccharide unit from one branch to the other,
exposing the 1-6 branch point for the debranching enzme to act. The glucan
transferase and the debranching enzme is a characteristic of one complex enzyme.

Glucose 6 Phosphatase (deficiency can cause Von Gierkes disease) is in the lumen
of the smooth endoplasmic reticulum. Genetic defects involving Glucose 6
Phosphate transporters can cause a variant of type I glycogen storage disease.

Regulation of Glycogenolysis and Glycogenesis is integrated by cAMP. Cyclic AMP


activates adenyl cyclase that will activate cAMP dependent protein kinase which will
in turn phosphorylate proteins. One of the proteins phosphorylated is glycogen
phosphorylase b converting it to glycogen phosphorylase a, an active phosphorylase
that will favor glycogenolysis. Another protein that is phosphorylated (enzyme) is
the glycogen synthase (phosphorylation of glycogen synthase promotes the b
conformation) resulting to inactivation of the enzyme thus will favor glycogenolysis
instead of glycogenesis.

In-born error of glycogen metabolism:


-

Genetic defect in the isoform of glycogen synthase will have the following
manifestations;

Post prandial state (after eating a carbohydrate meal) it will cause


high blood glucose, lactate and fatty acids. Excess glucose absorb in the

gut cannot be utilized for glycogenesis. It will be converted to lactate


(product of reduction of Pyruvate) and fatty acids (acetyl CoA produced
from oxidation of Pyruvate).

Fasting state manifestations include hypoglycemia (no available


stored glycogen in the liver to supply the circulation with glucose),
increased ketone bodies (an alternative fuel when blood glucose is low
produced during Beta oxidation). Beta oxidation produces acetyl CoA
which is a precursor for the synthesis of ketone bodies. Three enzymes
are responsible for ketone bodies formation; b Ketothiolase, HMG CoA
synthase, HMC CoA lyase.

Glycogen Storage Disease (Ex. Von Gierkes disease) genetic enzyme deficiencies
leading to accumulation of glycogen intracellularly with the following manifestations;

Hypoglycemia - liver enzymes Glycogen 6 phosphatase is defective

Weakness muscle enzymes for glycogenolysis is defective (decrease


utilization of glycogen during exercise or during physical activity)

Manifestations may also be dependent on the enzyme that is defective.

D. Pentose Phosphate Pathway or Hexose Monophosphate Shunt (HMS)


-

Two major functions


(1) formation of NADPH for synthesis of fatty acids and steroids, and
(2) synthesis of ribose (from ribose 5-phosphate) for nucleotide and nucleic acid
formation.

Glucose 6 phosphate is the substrate of the first enzyme (glucose 6 phosphate


dehydrogenase or G6PD) in the Pentose Phosphate Pathway

G6PD deficiency a genetic deficiency is a major cause of RBC hemolysis resulting to


anemia

Reaction occurs in the cytosol

Dehydrogenation reaction catalyzed by G6PD and 6-Phosphogluconate dehydrogenases


utilizes NADP as hydrogen acceptor.

The first phase (oxidative nonreversible phase) of the pathway reactions involve
dehydrogenation and decarboxylation to yield a pentose (ribulose 5 phosphate and
ribose 5 phosphate)

The 2nd phase (non-oxidative reversible phase) involves two enzymes, transketolase and
transaldolase that convert ribulose 5-phosphate back to glucose 6-phosphate by series
of reactions

III.

Lipid Metabolism
A. Fatty Acid Oxidation
-

Fatty acids are oxidized to Acetyl CoA and generates ATP

An aerobic process (requires Oxygen)

Occurs in the mitochondria

Each step in the oxidation process involves an acyl CoA derivative, a separate
enzyme, coenzymes NAD & FAD

Increased fatty acid oxidation leading to ketone body formation by the liver is a
characteristic of starvation and Diabetes mellitus

Free fatty acids are transported in the blood (long fatty acids bind with albumin and
short fatty acids are more water-soluble and exist in the unionized form or as an
anion

Oxidation of fatty acids require initially ATP and Coenzyme A for the activation of
the fatty acid catalyzed by Acyl-CoA synthetase (thiokinase)

Free Fatty Acids (FFA) cannot penetrate the inner mitochondrial membrane so it has
to undergo the following transformations;
o

Fatty acid converted to an active intermediate Acyl CoA


(FFA + ATP + CoA= Acyl CoA)

Acyl CoA diffuses through the outer mitochondrial membrane

Acyl CoA condenses with carnitine to produce Acylcarnitine + CoA by carnitine


palmitoyl-tranferase 1

Acylcarnitine is transported across the inner mitochondrial membrane by


carnitine acylcarnitine translocase

Acylcarnitine is converted back to carnitine + Acyl CoA by carnitine palmitoyltranferase 1

Acyl CoA is oxidized producing acetyl CoA (2 carbons is cleaved from the acyl CoA at
a time). The chain is broken between the alpha and the beta bond (beta oxidation).
Fatty acids with an even number of carbon atoms produce acetyl CoA. Those with
odd number carbon atoms produce acetyl CoA and Propionyl CoA. Propionyl CoA is

the glucogenic substrate derived from oxidation of odd numbered carbon fatty
acids.
-

Enzymes that catalyze the reactions and their coenzymes in Beta oxidation
1. Acyl Co A Synthetase CoA, ATP, Mg
2. Acyl CoA dehydrogenase FAD
3. delta2 -enoyl-CoA hydratase
4. L-(+)-3-hydroxyacyl-CoA dehydrogenase NAD
5. Thiolase CoA
Reactions 2-5 are repeated until completion of the oxidation process

Palmitate with 16 carbons will yield 8 acetyl CoA requiring 7 rounds of the Beta
oxidation cycle
o

4 mol of ATP is produced /cycle x 7 cycles = 28 mol ATP

10 mol of ATP/ TCA cycle x 8 cycles = 80

28 + 80 = 108 2 ATP (ATP used in the activation of the fatty acid in the first
reaction) = 106 mol of net ATP produced by 1 mol of palmitate.
NADH + H = 2.5 ATP; FADH2 = 1.5 ATP

Peroxisomes oxidize very long chain fatty acids and produce acetyl CoA and
Hydrogen peroxide (broken down by catalase). Dehydrogenation (NADH, FADH
produced) is not linked directly to phosphorylation (ATP production).

Oxidation of unsaturated fatty acids is modified. Same enzymes are utilized as in


saturated fatty acids except in that some enzymes are used like isomerases and
reductases.

B. Ketogenesis
-

Occurs in conditions causing high rate oxidation of fatty acids (ex. Uncontrolled
diabetes mellitus, starvation. Ketone bodies in normal well-fed mammals do not
exceed 0.2 mmol/L.

acetone bodies are acetoacetate, -hydroxybutyrate, acetone (acetone is produced


due to the spontaneous decarboxylation of acetoacetate)

acetoacetate and -hydroxybutyrate are inter-converted by a mitochondrial


enzyme, D()-3-hydroxybutyrate dehydrogenase (conversion is controlled by the
ratio of mitochondrial NAD/NADH)

the process of ketogenesis is as follows;

Two (2) acetyl CoA condenses (catalyzed by thiolase) to form acetoacetyl CoA.
The reaction is reversible.

Acetoacetyl CoA condenses with acetyl CoA (by HMG CoA synthase) to form
HMG CoA

HMG CoA is split into Acetyl CoA and acetoacetate by HMG CoA lyase

Acetoacetate is reduced (utilizing NADH) to 3-hydroxybutyrate: 3hydroxybutyrate is oxidized (using NAD) to acetoacetate. Both reactions are
catalyzed by 3-hydroxybutyrate dehydrogenase

Acetoacetyl CoA and 3Bhydroxybutyrate is readily oxidized by extrahepatic


tissues, acetone is not (volatile)

Increased production of ketone bodies results to ketonemia. Determination of


ketonemia is preferably done by determining ketone bodies in the blood rather
than in the urine. Renal threshold-like effects for excreting ketone bodies vary
from individuals.

Regulation of ketogenesis
1. Factors that regulate mobilization of fatty acids from adipose tissue (Fatty
acids are precursors of ketone bodies in the liver. The liver extracts 30% of
the fatty acids that pass through it).
2. CPT I activity (found in the outer mitochondrial membrane) catalyze the
condensation of Acyl CoA and carnitine
a. in the fed state, CPT I activity is low thus reducing -oxidation
(Malonyl-CoA, the initial intermediate in fatty acid biosynthesis
formed by acetyl-CoA carboxylase in the fed state, is a potent
inhibitor of CPT-I)
b. during starvation, the CPT I activity is increased (when
concentration of free fatty acids increases with the onset of
starvation, acetyl-CoA carboxylase is inhibited directly by acyl-CoA,
and [malonyl-CoA] decreases, releasing the inhibition of CPT-I and
allowing more acyl-CoA to be -oxidized
3. Acetyl CoA produced by -oxidation may either be oxidized in the TCA or is
utilized to form ketone bodies. The partition of acetyl-CoA between the
ketogenic pathway and the pathway of oxidation to CO2 is regulated so that

the total free energy captured in ATP which results from the oxidation of
free fatty acids remains constant as their concentration in the serum
changes. This may be appreciated when it is realized that complete
oxidation of 1 mol of Palmitate involves a net production of 106 mol of ATP
via -oxidation and CO2 production in the citric acid cycle (see above),
whereas only 26 mol of ATP are produced when acetoacetate is the end
product and only 21 mol when 3-hydroxybutyrate is the end product. Thus,
ketogenesis may be regarded as a mechanism that allows the liver to oxidize
increasing quantities of fatty acids within the constraints of a tightly coupled
system of oxidative phosphorylation.
a. Fall in Oxaloacetate can be caused by increased NADH/NAD ratio
due to -oxidation of fatty acids
b. Decreased NAD will reduce the activity of Malate dehydrogenase
(NAD is a coenzyme) thus lowering Oxaloacetate.
c. Oxaloacetate is needed in the oxidation of acetyl CoA oxidation of
acetyl CoA in the TCA will decrease with low Oxaloacetate
d. Pyruvate carboxylase is activated by increased levels of acetyl CoA
which in turn increases Oxaloacetate for gluconeogenesis (a
condition that occurs in starvation and uncontrolled Diabetes
mellitus).
o

Clinical Importance of fatty acid oxidation:


Carnitine deficiency may be due to:
a. impaired biosynthesis or increased renal clearance in the newborn
especially in premature infants.
b. loss of carnitine through hemodialysis
Symptoms of deficiency include hypoglycemia, which is a consequence of

impaired fatty acid oxidation and lipid accumulation with muscular weakness.
Treatment is by oral supplementation with carnitine.

1. Inherited CPT-I deficiency - affects only the liver; cause reduced fatty acid
oxidation and ketogenesis (because fatty acid will not be available in the
mitochondria for -oxidation), with hypoglycemia.
2. CPT-II deficiency acylcarnitine that was transported by the carnitine
acylcarnitine translocase to the mitochondrial matrix will not be converted
back to carnitine and acyl- CoA (precursor of -oxidation). It affects
primarily skeletal muscle and in severe cases the liver.
Treatment is by using sulfonylurea drugs (glyburide [glibenclamide] and
tolbutamide) which will reduce fatty acid oxidation and, therefore,
hyperglycemia by inhibiting CPT-I.
3. Inherited defects in the enzymes of -oxidation and ketogenesis also lead to
nonketotic hypoglycemia, coma, and fatty liver. Defects are known in longand short-chain 3-hydroxyacyl-CoA dehydrogenase (deficiency of the longchain en-zyme may be a cause of acute fatty liver of pregnancy). 3Ketoacyl-CoA thiolase and HMG-CoA lyase deficiency also affect the
degradation of leucine, a ketogenic amino acid
4. Jamaican vomiting sickness is caused by ingesting the toxin hypoglycin
(from the unripe fruit of the akee tree) toxin. This inactivates medium- and
short-chain acyl-CoA dehydrogenase, inhibiting -oxidation and causing
hypoglycemia.
5. Dicarboxylic aciduria is characterized by the excretion of C6C10 dicarboxylic acids and by nonketotic hypoglycemia, and is caused by a lack
of mitochondrial medium-chain acyl-CoA dehydrogenase.
6. Refsum's disease is a rare neurologic disorder due to a metabolic defect
that results in the accumulation of phytanic acid, which is found in dairy
products and ruminant fat and meat. Phytanic acid is thought to have
pathological effects on membrane function, protein prenylation, and gene
expres-sion.
7. Zellweger's (cerebrohepatorenal) syndrome occurs in individuals with a
rare inherited absence of per-oxisomes in all tissues. They accumulate C26
C38 polyenoic acids in brain tissue and also exhibit a generalized loss of

peroxisomal functions. The disease causes severe neurological symptoms,


and most patients die in the first year of life.
Ketoacidosis
8. Results from prolonged ketosis (a condition that includes ketonemia and
ketonuria). Ketosis is mild in starvation but severe in diabetes mellitus
9. Caused by acetoacetic and 3-hydroxybutyric acids. Both are moderately
strong acids and are buffered when present in blood or other tissues.
Continued excretion of increased quantity will deplete the alkali that buffer
the acids causing ketoacidosis. This may be fatal in uncontrolled diabetes
mellitus.

C. Fatty Acid Synthesis


-

Occurs in the cytosol

Glucose which is the main fuel in the diet is the primary substrate for lipogenesis

Inhibition occurs in type I Diabetes mellitus (insulin-dependent) and variations in


lipogenesis activity affects the nature and extent of obesity

Membrane fluidity is maintained by unsaturated fatty acids in phospholipids.


High ration of polyunsaturated/saturated fatty acids is beneficial in preventing
coronary artery disease.
o

De novo synthesis of fatty acids


1. Main pathway occurs in the cytosol
2. Synthesis occurs in the liver, kidney, brain, lung, mammary gland, and
adipose tissue
3. cofactor requirements include NADPH, ATP, Mn2+, biotin, and HCO3 (as a
source of CO2).
4. Acetyl-CoA is the immediate substrate (building block), produced from the
of oxidation of pyruvate (product of glycolysis) in the mitochondria. and free
palmitate is the end product
5. NADPH is made available primarily from pentose phosphate pathway
6. Acetyl CoA principal building block of fatty acid synthesis.
a. It is produced from oxidation of Pyruvate a product of glycolysis
in the mitochondria

b. It is transported into the cytosol as citrate (product of


condensation of acetyl CoA and Oxaloacetate) by a tricarboxylic
transporter. Citrate in the cytosol is cleaved back to acetyl Co A
and Oxaloacetate in the presence of CoA and ATP by ATPCitrate lyase (activity is increased in the well-fed state). Acetyl
CoA will be available for lipogenesis.
7. Oxaloacetate in the cytosol is reduced (using NADH as cofactor) to malate
by cytoplasmic malate dehydrogenase (sMDH-soluble malate
dehydrogenase).
a. Malate is transported inside the mitochondrion by tricarboxylic
transporter.
b. Malate is oxidized to Oxaloacetate (using NAD as cofactor) by
malate dehydrogenase (mMDH - mitochondrial MDH).
Oxaloacetate is replenished in the mitochondria as substrate for
TCA cycle.
c. Malate can also be oxidized (NADP as cofactor) by malic enzyme
resulting to decarboxylation. This will produce CO2, Pyruvate
and NADPH.
8. Fatty acid synthesis is catalyzed by a homodimer complex enzyme fatty acid
synthase.
9. Each polypeptide monomer contains 7 enzymes and an acyl carrier protein
(ACL). Each monomer can synthesize a fatty acid, thus one enzyme complex
can produce two fatty acids simultaneously.
10. Elongation of fatty acid synthesis occurs in endoplasmic reticulum catalyzed
by the enzyme fatty acid elongase. Malonyl CoA is the acetyl donor utilizing
NADPH as the reductant.
11. Malonyl CoA is formed from Carboxylation of Acetyl CoA by acetyl CoA
carboxylase. This is the most important reaction in the regulation of fatty
acid synthesis.
12. Nutritional state regulates lipogenesis
13. Excess glucose (after a fed state) and its derivatives are converted to fatty
acids. The rate of lipogenesis is high in the fed state.

14. In state of starvation (caloric deficiency), fatty acids are utilized to supply
acetyl CoA for energy (ATP) production. The rate of synthesis is low in
restricted caloric intake, high-fat diet, or a deficiency of insulin (in DM).
15. Short term regulation of long-chain fatty acid synthesis is due to allosteric
and covalent modification
16. Long term regulation is due to changes in gene expression of enzymes
involved
17. Regulation of Acetyl CoA carboxylase
a. allosterically activated by Citrate and by long chain acyl
molecules (negative feedback);
Long chain acyl molecules may accumulate due to
1) Increased lipogenesis will cause accumulation of long acyl
molecules due to decrease in the esterification of fatty acid
synthesized.
2) Increased lipolysis (breakdown of esterified FA) results to
increase in the production of fatty acids or its influx into the cell
b. covalently activated by dephosphorylation and inactivated by
phosphorylation
1) insulin triggers dephosphorylation acetyl carboxylase
is active in the dephosphorylated form. Also Inhibits
lipolysis and is important in gene expression and is
antagonized by glucacon.
a) Insulin also increases glucose uptake thus increasing
glycolysis. Glycolysis produces Glycerol-3-phosphate
and Pyruvate.
b) Glycerol-3-phosphate used substrate for esterification
of fatty acids
c) Pyruvate is the precursor for acetyl CoA
2) glucagon triggers phosphorylation acetyl carboxylase
is inactive in the phosphorylated form

3) epinephrine inactivates acetyl CoA carboxylase with


mechanism similar to the inactivation caused by
glucagon
18. some polyunsaturated fatty acids are nutritionally essentials like
Linoleic and -linolenic acids. Arachidonic acids are formed from
Linoleic FA.
a. Double bonds cannot be introduced beyond 9 position. Plants
can produce nutritionally essential fatty acids by their capability
to introduce double bonds at 12 and 15 positions.
b. The liver and some tissues can produce monounsaturated FA
from saturated FA by introducing (mostly) double bonds at 9
position by a 9 desaturase.
19. Essential fatty acids are required for the formation of prostaglandin,
thromboxane, leukotriene, and lipoxin
a. Deficiency of essential FA acids can have decreased growth
rates and reproductive deficiency in rats
o

Patients with retinitis pigmentosa are reported to have low blood


levels of DHA (Docosahexaenoic acid (DHA; 3, 22:6), which is
synthesized to a limited extent from -linolenic acid or obtained
directly from fish oils, is present in high concentrations in retina,
cerebral cortex, testis, and sperm. DHA is particularly needed for
development of the brain and retina and is supplied via the placenta
and milk.

20. Trans Fatty Acids


a. Small amounts of trans-unsaturated fatty acids are found in
ruminant fat (eg, butter fat has 27%),
b. The main source is in the human diet from partially
hydrogenated vegetable oils (eg, margarine).
c. Trans fatty acids compete with essential fatty acids and may
exacerbate essential fatty acid deficiency.

d. they are structurally similar to saturated fatty acids and have


comparable effects in the promotion of hypercholesterolemia
and atherosclerosis
21. Eicosanoids
Certain essential fatty acids (polyunsaturated) are derived from plants. Animals
have limited capacity to desaturate fatty acids. These essential polyunsaturated
fatty acids are used to form eicosanoids (20 carbons) which are the prostaglandins,
thromboxanes, leukotrienes, and lipoxins.
Prostaglandins and thromboxanes their function is to modify inflammatory
reaction. They also play a part in the regulation of the actions of the immune
system.
Thromboxanes derived from prostaglandin peroxides, influence platelet
aggregation (cause platelet aggregation) and contraction of arteries.
Leucotrienes a biologically active compound formed from white blood cells,
macrophages, mast cells etch in response to stimuli. It was formerly referred to as
slow reacting substances of anaphylaxis. It causes, bronchoconstriction, increase
vascular permeability and edema. It also recruits and activates white blood cells. It
has three to fourfold potency of effects as compared to histamine.
Lipoxins are anti-inflammatory substances derived from arachidomic acids. Their
expression can be induced by proinflammatory cytokines (INF-, IL-1).
Nonsteroidal anti-inflammatory drugs (aspirin ibuprofen) act as inhibitors of
prostaglandin synthesis.
Arachidonate may come from the diet but is usually derived from the 2 position of
membrane phospholipids by the action of phospholipse A2.
- Substrate for the synthesis of PG2 and TX2 series by the cyclooxygenase
pathways
- Substrate for the synthesis of LT4 and LX4 series by the lipooxygenase
pathways

2015 REVIEWER

Enzymes, Water & Iron

1. Lysosomes - Referred to as suicide bags of the cell, containing a variety of hydrolytic and
degradative enzyme
2. High specific heat - The ability of water to absorb and store a large amount of heat
3. Nucleus - The most prominent feature of the eukaryotic cell, serving as its
information center
4. Water as hydrophilic colloid system maintains body temperature for its main function
5. Iron in the body is absorbed in the ileum.
6. Transferrin is the glycoprotein involved in the transport or iron.
7. Ferritin is the major protein involved n the storage or iron.
8. Lactoferrin is the Iron that has anti-microbial effects thus can protect the newborn
9. Low ph is necessary in the absorption of iron
10. Protein digestion starts in the stomach where the acidic environment favors denaturation.
11. Excess NH4 from the breakdown of amino acids are converted into urea and excreted
12. Five carbon amino acids enter the citric acid cycle as Ketoglutarate
13. Example of a non-competitive inhibition - lead combines with the sulfhydryl group of enzymes.
14. Apoprotein is the protein, heat labile, non dialyzable portion a complex enzyme system.
15. Activity of enzymes is expressed in terms of velocity.
16. In an enzyme-substrate reaction, a large Km means a low affinity of enzyme for the substrate
17. Vitamin C as co-enzyme can act alternately as an oxidizing and reducing agent
18. The enzyme Lyase can bring about the cleavage of C-C, C-O, and C-N bonds in a substrate.
19. Km and Vmax are the two constants that are always measured whenever enzymes are
characterized.
20. Lyases are enzymes that catalyze the addition or removal of water, ammonia or carbon dioxide to
double bonds.
21. Alkaline phosphatase is the nonfunctional serum enzyme that is diagnostic of obstructive liver
diseases
22. Carbonic anhydrase requires zinc as cofactor.
23. ALA dehydratase is a zinc containing enzyme that is sensitive to the inhibition of lead.
24. Cyclooxygenase (COX1 and COX2) or Prostaglandin H synthase is inhibited by NSAIDS (ex.
Aspirin). COX2 is selectively inhibited by coxibs (ex. Celecoxib).
25. Anti-inflammatory corticosteroids inhibit transcription of COX2 but not COX1.
26. The quantitative value of the Michaelis constant or Km, is a measure of the relative affinity between
the substrate and enzyme
27. Acid phosphatase is valuable in the diagnosis of metastatic carcinoma of the prostate gland.
28. Ligases join two molecules along with breakdown of a pyrophosphate (P-P) bond
29. Oxygen is the H+ acceptor of oxidases
30. Acetylcholine stimulates the secretion of the following saliva, pancreatic enzymes, and gastric juices

BIOENERGETICS and BIOLOGICAL OXIDATION

1. The net ATP generated in the complete oxidation of beta-hydroxybutyrate is 26 ATPs


2. Twelve NADPH are required for complete synthesis of one (1) mole of
palmitic acid
3.
4.
5.
6.
7.
8.
9.

Oxidative phosphorylation is the major source of ATP in aerobic organisms.


Embden Myerhoff pathway is the primary pathway for the oxidation of glucose
Complete oxidation of one (1) mole of palmitic acid to CO2 and H2O, generates 131 ATP
Anaerobic glycolysis produces 2 moles of ATP per mole of glucose?
Phosphofructokinase is the Rate limiting enzyme and the major regulatory enzyme in glycolysis
Pyruvate dehydrogenase links glycolysis and the citric acid cycle
Oxidative phosphorylation is carried out by respiratory assembly located in the inner mitochondrial
membrane
10. A non-spontaneous endergonic cellular reaction be driven to completion by Coupling with an exergonic
reaction

PROTEIN AND AMINO ACID CHEMISTRY/ METABOLISM

1. Primary structure of proteins determined by the sequence of amino acids in the polypeptide chain
and sulhydril bridges
2. Secondary - the folding of short (3- to 30-residue), contiguous segments of polypeptide into
geometrically ordered units. Ex. Helix structure
3. Tertiary - the assembly of secondary structural units into larger functional units such as the mature
polypeptide and its component domains
4. Quaternary - the number and types of polypeptide units of oligomeric proteins and their spatial
arrangement

5. Glutamine is the amino acid that serves as the major mode for disposing ammonia from the brain
6. Transamination of pyruvate will produce alanine
7. Tyrosine is the amino acid precursor of catecholamines.

8. Tryptophan is the precursor of serotonin


9. Leucine is purely ketogenic.
10. Urea is synthesized in the liver and the major pathway for nitrogen excretion in humans.
11. Fumarate links the urea cycle and the citric acid cycle.
12. The functional group of tryptophan is the indole grp.
13. Glutamate dehydrogenase funnels amino nitrogen from glutamate to urea. The most active enzyme
involved in oxidative deamination
14. The metabolism of tryptophan leads to the production of small amounts of nicotinic acid in humans.
15. Lysine, threonine, proline and hydroxyproline do not participate in transamination reactions.
16. The coenzyme pyridoxal phosphate (PLP) a derivative of vit. B6 is present at the catalytic site of all
Aminotransferases.
17. Glutamine formation is the major means by which the brain detoxifies ammonia.
18. Carbamoyl phosphate synthetase requires N-acetylglutamate as positive modulator.
19. -ketoglutarate depletion in severe liver disease is the immediate cause of coma.
20. All of these three conditions cause Phenylketonuria - Deficiency of phenylalanine
monooxygenase, deficiency of NADPH, and deficiency of dihydrobiopterin reductase
21. Homocystinuria is an inborn error of methionine metabolism which is manifested by skeletal
deformities and dislocation of the lens of the eyes

INORGANIC ELEMENTS/VITAMINS, MINERALS & TRACE ELEMENTS


1. Inorganic elements are needed to provide a suitable medium for protoplasmic activity, play a role in
osmotic phenomena and are involved in acid-base equilibra.
2. Miscible calcium pool is the freely moving calcium in tissue, extracellular fluid and blood.
3. Vitamin D aids the absorption of calcium and phosphates in the GIT.
4. Gastric acidity reduces dietary iron to ferrous form (the form that is absorb in the intestines)
5. Extrahepatic tissues like the skeleton and heart muscle can utilize acetoacetic acid, B-hydroxybutyric
acid, and Ketoacids but not acetone as source of fuel
6. Chylomicrons produces the milky appearance of blood following a heavy intake of fat, and can be
removed only by the action of lipoprotein lipase and heparin.
7. Cholesterol can give rise to bile acids, steroid hormones and Vitamin D.
8. Ascorbic acid is an important anti oxidant because it inhibits the formation of nitrosamines during
digestion.
9. Vit E deficiency may lead to anemia in the prematures due to red blood cell hemolysis
10. Thiamine is a cofactor of transketolase an enzyme of the pentose phosphate pathway,
NUCLEIC ACIDS
1. The ability of the products in purine and pyrimidine nucleotide de novo pathways to inhibit the
formation of PRPP is responsible for the concerted regulation between
these two pathways.
2. Small nuclear RNA has catalytic splicing activity and converts primary transcript to its mature
form.
3. elongation, processivity and proofreading are the three important properties of DNA polymerases
4. Adherence to the Watson-Crick base pairing rules is a common characteristic of replication and
transcription
5. TATA box is important in transcription because binding of DNA binding protein to this box
enhances transcription.

6. Degeneracy of the genetic code is an important feature of the genetic code that may protect the
codon in the event of a single base substitution:
7. Single base insertion or deletion on the genetic code changes the reading frame and result to a
frameshift mutation.
8. Tumor p53 suppresor protein plays a key role in both the G1 and G2 chekpoint control.
9. Southern blot is the technique involved in the analysis of DNA.
10. Cosmids are used for cloning DNA fragment with a length of 400,000 bp
11. The enzymes required for the synthesis of cDNA are, reverse transcriptase, DNA ligase,
andRnase H
12. DNA chips(microarray) is the method based on the preparation of large arrays of oligonucleotides
on miniaturized solid supports for analysis of DNA sequence.
13. Antibiotic resistance gene is an important feature of a cloning vector because it will allow
screening of the host (successfully transfected host)
14. Dnase 1 an enzyme that does not form phosphodiester bonds.
15. DNA amplification is the diagnostic technique to use in patients at with sickle cell anemia or at
risk of this disease.
16. DNA methylation is the process that occurs at the 5-position of Cytidine and is often correlated
with gene inactivation
17. A specific nuclease detects damaged areas following ultraviolet damage to DNA in the skin.
18. Northern Blot Analysis Detects RNA molecules
19. RNA polymerase synthesizes RNA primer to initiate DNA synthesis
20. The function of a promoter site on DNA is to Initiate transcription

LIPID CHEMISTRY / LIPID METABOLISM


1. high density lipoprotein - is inversely related to the incidence of
coronary atherosclerosis ( HARPERs 25 th ch 27 pp 268-271)
2. very low density lipoproteins- The lipoprotein that serves to transport triacylglycerol
from the liver to the different extrahepatic tissues:
(Harpers Ch 27 p 268-271)
3. apolipoprotein D - the apolipoprotein that serves as lipid transfer
protein ( Harpers ch 27 p 271)
4. Chylomicrons lipoproteins that have the highest total lipid content
( Harpers p 268)
5. chylomicrons - the lipoproteins that have the highest triacylglycerol content
- is elevated in Type I Hyperlipidemia
(Harpers Ch 27 p 268-271)
-

produces the milky appearance of blood following a


heavy intake of fat, and can be removed only by the action of
lipoprotein lipase and heparin

transports exogenous triglycerides

6. chylomicrons the fraction of the plasma lipoproteins that is located closest to the
negative pole when separated by electrophoresis on agarose gel
(Harpers
Ch 27 p 268-271)

7. apolipoprotein A-II the apolipoprotein that serves as inhibitor of


lecithin:cholesterol acyltransferase (LCAT)
( Harpers ch 27 pp 270-271)
8. Triacylglycerides is the form of lipid that stores energy
9. malate Pyruvate the step that generates NADPH In the shuttle of mitochondrial
acetyl coenzyme A to the cytosol for fatty acid synthesis
( Harpers ch 24 pp238-239)
10. Beta hydroxybutyrate acetoacetate the steps in the metabolism of ketone bodies
that generate NADH
( Harpers ch 24 p 244-245)
11. Cytosol where cholesterol and fatty acid synthesis occur
( Harpers ch 28 p285)
12. Krabbe's Disease a condition which is characterized by pathologic
accumulation of galactocerebroside in the affected tissues.
( Harpers ch 27 p 267t)
13. Liver where ketone bodies are synthesized from fatty acids
major site of fatty acid synthesis
(Harpers ch 24 p242) (Harpers ch 23 p 230-231)
14. Brain utilizes ketone bodies as much as 75% for its energy substrate during
uncontrolled diabetes mellitus or starvation ( harpers ch 29 p 301)

15. Acetone produced from spontaneous decarboxylation of acetoacetate


( Harpers ch 24 p 242-243)
is not utilized as energy source, is a volatile substance
16. Ganglioside lipids that accumulates in tissues of patient with
Tay-Sachs Disease

17. Citrate the compound that is transported out of the mitochondria that contains the
acetate group needed for fatty acid biosynthesis in the cytosol

18. Carnitine ferries the fatty acids (acyl CoA) through the inner mitochondrial
membrane for beta-oxidation in the matrix

19. Mitochondrial matrix where the activation of medium chain and short fatty acids
occurs in the for beta-oxidation
(Harpers pp 238-239)
20. Malonyl coenzyme A is the product formed in the committed (rate limiting) step of
fatty acid synthesis
( Harpers Ch 23 pp 230)

inhibits Carnitine palmitoyl transferase I thus inhibiting beta-oxidation in


the feed state
21. Phospholipids and Cholesterol the fats that may still be found in the tissues after a
long period of starvation.

22. Cholesterol - is the precursor for the synthesis of bile acids (metabolic product),
Vitamin D, and Steroid hormones

23. Cardiolipin Structure is composed of three glycerol, two phosphoric acid and 4 fatty
acids
24. Thromboxane - the eicosanoids that can promote platelet aggregation

25. Lecithin lipid that acts as surfactant and deficient in cases of Respiratory Distress
syndrome
26. Palmitic acid is the end-product of extra-mitochondrial lipogenesis
27. Acetyl CoA is the two carbon product released by the action of thiolase in the betaoxidation of fatty acids
28. Carnitine transport is the committed step in beta-oxidation
29. HMG-CoA reductase enzyme that catalyze the rate-limiting step in cholesterol
synthesis

30. Isopentenyl pyrophosphate the formation of which is the most expensive stage in
the biosynthesis of cholesterol
31. alpha lipoprotein functions in the reverse transport of cholesterol in the blood.
32. Insulin the hormone which is antilipolytic
33. Hormone-sensitive lipase the major regulatory enzyme in lipolysis
34. Dihydroxyacetone phosphate the source of glycerol 3-phosphate for triglyceride
synthesis in adipose tissue
35. acetoacetic acid is produced by the reaction that is catalyzed by HMG-CoA lyase
36. Phospholipase C hydrolyzes phospholipids specifically phosphatidylinositol-4,5bisphosphate (PIP2) and produces second messengers inositol triphosphate (IP3)
and diacylglycerol (DAG)
37. Ceramide precursor of sphingolipids
38. Clyclooxygenase catalyze the production of prostaglandins, thromboxanes, and
prostacyclins
39. Polyunsaturated fatty acids up-regulate LDL
40. HMP shunt main source of NADPH for lipogenesis
41. Substrate level phosphorylation direct phosphorylation of ADP to produce ATP (An
example of substrate level phosphorylation that occurs in glycolysis is the production of
ATP when 1,3 bisphophoglycerate is converted into 3-phosphoglycerate).
main source of ATP formation in brown adipose
tissue

42. Lovastatin inhibitor of HMG CoA reductase


43. HMG CoA reductase - repressed by cholesterol

44. LDL transports the highest proportion of cholesterol

45. Acetyl CoA carboxylase catalyzes the initial and controlling step in lipogenesis

46. Ascorbic acid - is needed in the rate limiting reaction of bile acid synthesis

47. [NADH]/NAD+] ratio increase levels is the biochemical explanation for fatty liver and
hyperuricemia in chronic alcoholics

48. Fatty acids the major source of energy for oxidative metabolism in the heart

49. Carnitine shuttle transport system that shuttles activated fatty acid molecule from the
cytoplasm to the inner mitochondrial membrane during -oxidation of fatty acids
50. Apo B-48 is the apoprotein found exclusively associated with chylomicrons

B. Carbohydtrate chemistry/ Carbohydrate metabolism

1. -D glucose and -L glucose are Enantiomers. What are enantiomers?


2. glycoside - is the sugar derivative produced by the reduction of the carbonyl group on a
monosaccaharide
3. galactose is the primary hexose, which is a constituent of glycolipids and
glycoproteins
4. Choindroitin sulfate is the glycosaminoglycan that is found in large amount in
cartilages
5. sorbitol - the compound that is the probable causative factor in the development of
cataract in patients with diabetes mellitus
6. McArdles disease - the glycogen storage disease resulting from the deficiency of
muscle phosphorylase
7. Fructose - the major energy source for spermatozoa in seminal fluid?
8. an enlarged liver is the likely manifestation of a patient with von Gierkes disease
9. In humans, liver glycogen stores are adequate up to 12 hours without support from
gluconeogenesis
10. Lactate is the end product of anaerobic metabolism
11. Peptidoglycan layer is responsible for the gram negativity or gram positivity of bacterial cell
wall
12. Muscle lacks glucose-6-phosphatase so that it cannot contribute glucose to the blood. Glycogen
in muscles is used to supply glucose 1 phosphate that is utilized for glycolysis. G1P is converted
to G6P by phosphoglucomutase.
13. Citrate is the citric acid cycle intermediate which is the source of acetyl CoA for
extramitochondrial palmitate synthesis

14. fructose-2,6-bisphosphate is a potent activator of Phosphofructokinase 1 and an inhibitor of


fructose-1,6-bisphosphatase. It is synthesized from fructose 6 phosphate by
phosphofructokinase-2. It favors glycolysis.
15. Phosphoenolpyruvate carboxykinase is a regulatory enzyme of gluconeogenesis
16. The carbon skeletons of the following amino acids enter Krebs citric acid cycle via alphaketoglutarate for gluconeogenic conversion
17. Brain - The organ most vulnerable to hypoglycemia because of its utter dependence on
circulating blood glucose for energy
18. The importance of some derived monosaccharide - Phosphorylation of glucose as glucose-6phosphate traps the hexose for entry into carbohydrate metabolism.
19. The most important monosaccharide in man is glucose because it is the important substrate for
cellular glycolysis.
20. An important feature of the electron transport chain it provides most of the energy captured in
metabolism.

BIOCHEMISTRY

REFERENCES :
1. Biochemistry by Harper, 25th edition
2. Textbook of Biochemistry with Clinical Correlation by Thomas Devlin
3. Biochemistry Campbell 3rd edition
4. Biochemistry a Case Oriented Approach by Mosby
5. Biochemistry by Orten and Newhaus
6. Molecular Biology of the Cell by Alberts

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