1

Biological Oxidation:

When a substance exists both in the reduced state and the oxidised state , the
pair is called a REDOX COUPLE.
The redox potential of this couple is estimated by measuring the EMF of a
sample half cell
connected to a standard half-cell.
LOWER AFFINITY FOR ELECTRONS = NEG. REDOX POTENTIAL = STRONG
REDUCING AGENT AND VICE VERSA.
cytochrome c and a have high redox potential (.22 and .29)
Oxidases:
Catalyze the removal of hydrogen from a substrate with the involvement of
oxygen as a H acceptor.
Aerobic Dehydrogenases: These enzymes catalyze the removal of hydrogen
from a substrate but oxygen as well as other substances can act as acceptor .
These enzymes are flavoproteins and the end product is usually hydrogen
peroxide H202
Anaerobic Dehydrogenases: Dehydrogenases use coenzymes
nicotinamides & riboflavin - as hydrogen carriers
Cytochomes :- All cytochromes (except CYTOCHROME OXIDASE ) are anaerobic
dehydrogenases
Monooxygenases

incorporates one atom of oxygen into the

substrate & the other is reduced to water. Phenlyalanine hydroxylase ,

Tyrosine hydroxylase , Tryptophan hydroxylase
-Microsomal cyt.P450 monooxygenases are involved with drug
metabolism
- Mitochondrial cyt P450 monooxygenase
Substrate level phosphorylation: Bisphosphoglycerate kinase
( Glycolysis)
(1,3 bisphosphoglycerate 3-phosphoglycerate) Pyruvate
kinase (Glycolysis)

(Phosphoenol pyruvate Pyruvate)

Phosphagens :act as storage forms of high-energy phosphate and include creatine

phosphate
Mitochondria: Intermembrane:
Outer-acyl Coa sythetase,
Glycerol
phosphate
, acyl transferase
Adenylyl
kinase,
creatine
kinase
membrane:
impermeable
to ions
and most1-4)
compounds Inner Mitochondria
ATP
Synthase,
ETC
(complexes
Matrix: B-oxidation, TCA cycle enzymes, Citric acid
cycle enzymes,
Pyruvate dehydrogenase

Mitochondria membrane is impermeable to NADH- need malate

aspartate shuttle-used in the liver, kidney and heart (malate to
OAA to aspartate)
Also need Glycerol 3-phospate shuttle for muscle and brain (require
FAD)
NADH-CoQ Dehydrogenase (Complex I)- Contains a flavoprotein (Fp)- FMN (Favin
mono nucleoide): prosthetic group and an iron-sulphur protein (Fe-S).
-at this moment 1 ATP is produced
Succinate-CoQ Dehydrogenase (Complex II)
-The 3 major enzyme systems that transfer their electrons directly to ubiquinone
are:
Succinate dehydrogenase
Fatty acyl CoA dehydrogenase
Mitochondrial glycerol phosphate dehydrogenase.
CoQ-cytochrome c Reductase (Complex III)
Cytochrome c Oxidase (cyta-a3) (Complex IV)
Mobile complexes:
Co-enzyme Q or ubiquinone
Cyt C-Contains one heme prosthetic group .
It collects electrons from Complex III and delivers to Complex IV.
It is also the mediator of apoptosis (programmed cell death)
Flow of electrons:
for NADH Complex 1 -> complex 3 -> complex 4
for FADH Complex 2 -> complex 3 -> complex 4
Chemiosmotic theory- The transport of electrons from inside to outside
of inner mitochondrial membrane is accompanied by the generation of a
proton gradient across the membrane.
Protons accumulate outside the membrane creating an electrochemical
potential.
This drives the synthesis of ATP by ATP synthase.
Oligomycin- blocks ATP synthase, blocks H+ from coming into to membrane

Fo complex:
O STANDS FOR OLIGOMYCIN
Made of 12 subunits . H+ passes through each subunit from membrane
space to inner space rotating the Fo complex
F1 complex: Has 9 polypeptide chains ,(3 alpha , 3 beta , 1 gamma , 1 sigma , 1
epsilon)
the chains have binding sites for ATP and ADP and beta chains have catalytic
activity.
ATP SYNTHESIS NEEDS Mg +2 IONS
ADP and Pi bind the alpha subunit
Binding change mechanism - conformational change of beta subunits causes
release of ATPs from the complex.
ATPs formed in the mitochondrial matrix are translocated to cytosol by ATP/ADP
translocase
only 32 ATPs may be generated from glucose .
Inhibitor of ATP Synthesis:
Site : COMPLEX 1 to Co Q
Alkylguanide(guanethide), hypotensive drug
Rotenone ( insecticide and rat poison)
Chlorpromazine (tranquiliser)
Barbiturates (sedative)
Pericidin (antibiotic)
Site :COMPLEX III to Co Q (ubiquine)
BAL BRITISH ANTI LEWISITE WAR GAS
Napthoquinone
Site : Complex IV inhibitors
Carbon monoxide
Cyanide
Azide
Hydrogen Sulphide
Site : between succinate dehydrogenase and CoQ
Carboxin
Malonate : competetive inhibitor of Succinate DH
Actractlyoside inhibits translocase whereas oligomycin acts
through one of the proteins present in Fo-Fi stalk.
Uncouplers:
2,4 dinitro phenol,
2,4 dinitro cresol
CCCP (Chloro carbonyl cyanide phenyl hydrazone)
THERMOGENIN in brown adipose tissue

Thyroxine
MELAS: complex1 or complex 1 and 4 disease
Mitochondrial encephalopathy
Lactic acidosis
Stroke like episodes.
Lebers Hereditary Optic Neuropathy LHON complex -3 defect
Degeneration of Retinal ganglion layer.
Kearns-Sayre syndrome- Oculocraniosomatic neuromuscular disease with
ragged red fibers
Leighs disease- complex 4 defect, fatal by the age of 2
Q. A comatose laboratory technician is rushed into the emergency room. She dies
while you are examining her. Her most dramatic symptom is that her body is literally
hot to your touch, indicating an extremely high fever. You learn that her lab has been
working on metabolic inhibitors and that there is a high likelihood that she
accidentally ingested one. Which one of the following is the most likely culprit?
Barbiturates
Piericidin A
Dimercaprol
Dinitrophenol
Cyanide
Q. A 53-year-old, previously successful man recently lost his job and is under
investigation for racketeering. His wife returns home to find him slumped over the
steering wheel of his idling car in the closed garage. He is unresponsive and has a
cherry color to his lips and cheeks. Which of the following is inhibited?
Complex I of the ETC
Cytochrome oxidase
The ATP-ADP antiporter
The F0 component of the F0-F1 ATPase
The F1 component of the F0-F1 ATPase

TCA Cycle

The citric acid cycle is the final common pathway for the oxidation of carbohydrate,
lipid, and protein because glucose, fatty acids, and most amino acids are
metabolized to acetyl-CoA or intermediates of the cycle.
-If hepatic cells are damaged as in acute hepatitis or replaced by connective tissue
(as in cirrhosis) there will be damage
PDH : E1 - Thiamine pyro phosphate (TPP) (B1)
E2 Lipoic acid
Co-enzyme-A (Pantothenic acid)
E3 NAD Niacin (B3)
FAD Riboflavin (B2)
TLCFN: tender, loving, care for nancy:
3 Enzymes:1)PDH,
2)-KGDH(TCA cycle)
3)Branched keto acid dehydrogenase
PDH is IRREVERSIBLE ( Fats cannot be converted to glucose.)
-1 NADH is generated =2.5 ATP
PDH is inhibited by its end product Acetyl Coa
PDH kinase inactivation of enzyme
PDH Phosphatase - activation (insulin in adipose can activate it)
Congenital Lactic acidosis:
-Deficiency of Pyruvate Dehydrogenase enzyme.
Inability to convert Pyruvate to Acetyl co-A.
Shunted to Lactate Dehydrogenase to form Lactic Acid.
Deficient NADH leading to deficient ATP
Lactic acidosis, severe psychomotor retardation, damage to brain stem, cortex etc..,
Fluoroacetate- blocks aconitase
Arsenite- alpha keto glutarate dehydrogenase complex
Malonate- block succinate dehydrogenase
ATP Substrate level phosphorylation- enzyme used in succinate
thiokinase/succinate Co A synthetase

OAA is viewed as a catalyst , which enters into the cycle , causes complete oxidation of
acetyl CoA , and is regenerated in the end without any loss.
Oxidation of fats need the help of Oxaloacetate which enters into the cycle and is
regenerated in the end . The major source of OAA is Pyruvate. (Carbohydrate)
Excess carbohydrates are converted to neutral fats via citrate and ATP-citrate lyase
but not vice versa because Pyruvate dehydrogenase step is irreversible.
TCA cycle plays an important role in Gluconeogenesis , Transmination and
Deamination.
OAA to phospoenol pyruvate to glucose -pathway of gluconeogenesis
a-ketoglutarate to glutamate and vice versa (transmination and deamination)
Precursor of heme through succinyl Co-A
Pyruvate to OAA= pyruvate carboxylase
Pyruvate to malate=malate enzyme
allosteric inhibition of citrate synthase by ATP and long-chain fatty acyl-CoA.
Increased ATP and NADH will inhibit isocitrate dehydrogenase, so no alpha ketoglutarate ,
and theres a build of citrate and citrate inhibits pfk-1 so no glucolysis
Beriberi , Wernickes encephalopathy and Korsakoffs psychosis (WK syndrome)in
Thiamine deficiency is due to failure of TCA cycle ( Pyruvate dehydrogenase and a-ketoglutarate dehydrogenase)
Congenital deficiency of Pyruvate dehydrogenase Lactic acidosis and neurodeficit.
Congenital deficiency of Pyruvate carboxylase OAA is deficient failure of sparking of
TCA severe mental retardation , lactic acidosis.
Q. During a myocardial infarction , the oxygen supply to an area of the heart is
dramatically reduced , forcing the cardiac myocytes to switch to anaerobic
metabolism.Under these conditions , which of the following enzymes would be
activated by increasing intracellular AMP?
a. Succinate dehydrogenase
B. PFK1
C. GLUCOKINASE
D. PDH
E. LDH
Q. Which of the following is required for cholesterol synthesis in hepatocytes?

A. Citrate shuttle
B. Glycerphosphate shuttle
C. Malate-Aspartate shuttle
D. Carnitine shuttle
E. Adenine nucleotide shuttle
A 55 year old alcoholic was brought to the emergency department by his friends.
During their usual nightly gathering at the local bar, he had passed out and they had
been unable to revive him.
Q. The physician ordered an injection of thiamine followed by overnight parental
glucose. The next morning the patient was alert and serum thiamine was normal and
blood glucose was 73mg/dl. The IV line was removed and he was taken home. At the
time of discharge from hospital which of the following proteins would have no
significant physiological activity in this patient?
Malate dehydrogenase
Glucokinase
GLUT 1 transporter
PFK-1
Glucose 6 PO4 dehydrogenase
Carbohydrates
Clinical application :- Benedicts test is a bed side test for
detection of reducing sugar in urine(Clinitest, Urine)
Sucrose- Bypasses metabolic check points- OBESITY
Lactose intolerance: Deficiency of enzyme lactase in brush border epithelium
Lactulose: Used in the treatment of hepatic encephalopathy
Metabolized by the colonic bacteria to acidic products CAUSES PURGATION
Promotes the excretion of ammonia in feces as protonated ammonium ions
Homoglycan: STARCH,GLYCOGEN, CELLULOSE, INULIN, DEXTRANS, CHITIN
Starch: Composed of AMYLOSE & AMYLOPECTIN
Liver glycogen - first line of defense against declining blood glucose levels especially
between meals.

Dextrans: In hypovolemic shock, given intravenously increases blood

volume
Homoglycan
Chondroitin sulfate- most abundant, found in cartilage, tendon and ligament
Dermatan sulfate-Helps in wound repair and fibrosis.
Keratan sulfate-Absence of glucuronic acid, KSI CORNEA
KS II Loose connective tissue
Heparin-Found in mast cells, Acts as an anticoagulant binds antithrombin III and
activates it
Heparan sulfate-Found in basement membrane and cell surface, Skin
fibroblasts and aortic walls
Hyaluronic acid- Not sulfated, Not linked to any protein Found in synovial fluid of
joints, vitreous humor of eye.
Proteoglycans-Proteoglycans are proteins that contain covalently linked
glycosaminoglycans. ( GAGS 95 % PROTEINS 5% approx.)
Degradation of GAG: Degraded by lysosomes.Enzymes acid hydrolases.
Extracelluar GAGs are brought inside by phagocytosis.
Muccopolysacharides:
Hurler Syndrome: Key features: corneal clouding, mental retardation,
micrognathia, coarsening of facial features with macroglossia, inguinal
and abdominal hernias, retinal degeneration.
Hunter- no corneal clouding
Sanfilippo-Severe neurological involvement
Morqoiu- Severe skeletal dysplasia.
Q. A 30-month-old child presents with coarse facial features, corneal
clouding, hepatosplenomegaly, and exhibiting disproportionate short-trunk
dwarfism. Radiographic analysis indicates enlargement of the diaphyses of
the long bones and irregular metaphyses, along with poorly developed
epiphyseal centers. Other skeletal abnormalities typify the features
comprising dystosis multiplex. The childs physical stature and the analysis
of bone development indicate the child is suffering from which of the
following disorders?
(A) Hunter syndrome
(B) Hurler syndrome
(C) Maroteaux-Lamy syndrome
(D) Morquio syndrome type B
(E) Sanfilippo disease type A
Gluconeogensis:
Liver and Kidney are the major gluconeogenic tissues
Glucogenic amino acids

Lactate
Glycerol
Propionate
Proprionate- go to succinyl CoA to intermediates of TCA (remember
methymalonyl CoA isomerase is here and needs B-12 coenzyme
Three nonequilibrium reactions in glycolysis catalyzed by hexokinase,
phosphofructokinase and pyruvate kinase, prevent simple reversal of
glycolysis for glucose synthesis.
Glucagon and epinephrine inhibit glycolysis and stimulate
gluconeogenesis in the liver by increasing the concentration of cAMP.
-They also affect the concentration of fructose 2,6-bisphosphate which is the most potent
positive allosteric effector of of Phosphofructokinase -1 and inhibitor of Fructose 1,6
bisphosphatase .
Fructose 2, 6 bis- activated by insulin, inactivated by glucagon

Acetyl -CoA as an is an allosteric activator of Pyruvate carboxylase-Acetyl -CoA

as an is an allosteric activator of Pyruvate carboxylase.
Malfunctioning of citric acid cycle def of oxaloacetate
ALCOHOL DEHYDROGENASE- convert alcohol to Acetaldehyde to Acetate
creating NADH
EXCESS LACTATE from PYRUVATE
Excess Malate FROM OAA
Excess Glycerol 3 P from DHAP
No or less Gluconeogenesis!!Hypoglycemia
Q. Immediately after completing a 25-mile marathon race, a healthy 24-yr old man
was extremely dehydrated and thirsty. He quickly consumed a 6-pack of ice-cold beer
and shortly thereafter became very weak and light-headed and nearly fainted. He
complained of muscle cramping and pain. What is the most probable cause ?
Excess lactate in blood
Excess Alcohol in blood
Excess NADH
Dehydration
Electrolyte imbalance

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Q. Which of the following enzymes can be induced genetically by hormones in a

person with prolonged history of fasting?
Glucokinase
Pyruvate Carboxylase
PFK-1
Acetyl co-A Carboxylase
Phosphofructokinase
Q. In the citric acid cycle, succinate thiokinase catalyzes the cleavage of the succinyl
Co-A to succinate with formation of a high energy compound. This compound can
then be used by the body in which of the following biochemical pathways?
Oxidative phosphorylation
Gluconeogenesis
Formation of creatine phosphate
Cholesterol synthesis
Fatty acid synthesis
Glycolysis
Aerobic Glycolysis : formation of Pyruvate as end product with production of ATP and NADH
when oxygen is available
Anaerobic Glycolysis : formation of lactate as end product with production of only ATP in the
absence of oxygen .
Allows continuous production of ATPs in cells without mitochondria or cells deprived of
oxygen
pfk-1 =rate limiting step
-7ATP formed
NADH produced during anaerobic Glycolysis is utilized during lactate dehydrogenase step
Iodate acetate- inhibits G3 P dehydrogenous
Flouride blocks enolase
Hormonal regulation (mainly liver): Insulin favors Glycolysis and Glucagon inhibits
Glycolysis
Hexokinase- found everywhere, low affinity, work at normal levels
Glucokinase- found in liver and beta cells of pancreas, high affinity work at high
levels
Glucagon inhibit pyruvate kinase by cAMP and protein kinase A
Insulin activate pyruvate kinase through protein phosphatase
Second most common cause for enzyme deficiency related hemolytic anemia.
Def causes decreased ATP production in RBCs

11

Decreased energy to fuel the pumps required to maintain the biconcave, flexible
shape of RBCs.Red cell damage and phagocytosis premature death and lysis
hemolytic anemia (chronic hemolysis) Absense of Heinz bodies ( to differentiate
G6PD def)
Q. Under conditions of anaerobic glycolysis, the NAD+ required by glyceraldehyde-3-phosphate
dehydrogenase is supplied by a reaction catalyzed by which of the following enzymes?
Glycerol-3-phosphate dehydrogenase
Alpha-ketoglutarate dehydrogenase
Lactate dehydrogenase
Malate dehydrogenase
PDH
Q, After consumption of a carbohydrate-rich meal, the liver continues to convert glucose
to glucose-6-phosphate. The livers ability to continue this processing of high levels
of glucose is important in minimizing increases in blood glucose after eating. What
is the best explanation for the livers ability to continue this conversion after eating
a carbohydrate-rich meal?
The Hepatocyte cell membranes permeability for glucose-6-phosphate
The high maximum reaction rate (high Vmax) of Glucokinase
The inhibition of Glucokinase by high glucose-6-phosphate
The lack of Glucokinase level regulation by insulin
The low Michaelis-Menten (Km) constant of Glucokinase
Various fates of pyruvate : 1. to lactate 2. to Acetyl Coa 3. to OAA 4. to alanine (using
pyridoxal phosphate- a transamination b6)
Q. Which of the following is required for cholesterol synthesis in hepatocytes?
A. Citrate shuttle
B. Glycerphosphate shuttle
C. Malate-Aspartate shuttle
D. Carnitine shuttle
E. Adenine nucleotide shuttle

HMP/Pentose Pathway
NADPH required for biosynthesis of fatty acids and steroids.
Generation of Ribose-5-phosphate for nucleotide synthesis

12

Interconversion of carbohydrates into glycolytic and gluconeogenic intermediates.

Oxidative pathway irreversible
- mainly occurs in tissues which require NADPH (irreversible)
Non oxidative pathway reversible
- Occurs in the tissues which require ribose for nucleotide synthesis.

Transketolase-Transfers a 2-C unit (C1 AND C2 ) of a ketose to

aldehyde C of aldose
Transaldolase-Transfers a 3-C unit (dihydroxyacetone) from
Seduheptulose 7P to glyceraldehyde 3P
Source of NAD: tryptophan and niacin, for NADPH Cytosolic Isocitrate
dehydrogenase: and Malic enzyme:
Wernicke-Korsakoffs syndrome :- Genetic disease where a mutation in gene for
transketolase which decreases the affinity of enzyme transketolase for Thiamine
pyrophosphate (TPP)
Treatment :- Give thiamine
Beri Beri Thiamine deficiency
ALCOHOL -INHIBITS THIAMINE ALCOHOL, VERY LITTLE THIAMINE IN
ALCOHOLIC BEVERAGES, POOR NUTRITION IN ALCOHOLICS
CHRONIC ALCOHOLICS WILL HAVE WERNICKES KORSAKOFFS SYNDROME +
SYMPTOMS OF THIAMINE DEFICIENCY
Uses of NADPH:
REDUCTIVE BIOSYNTHESIS e.g.
Biosynthesis of steroids
Fatty acid synthesis
Drug metabolism cytochrome p 450 system
Glutathione reductase
NADPH Oxidase respiratory burst phagocytosis. by neutrophils and macrophages
Reduction of hydrogen peroxide: NADPH aids in synthesis of superoxide
radical during respiratory burst. Superoxide dismutase gives you
hydrogen peroxide, then myloperoxidase gives you hypochlourus acid to
kill the bacteri
Function of reduced glutathione: acts along with Glutathione Peroxidse reduce
hydrogen peroxide to water in RBCs. (Neutralization of free radicals)

13

Deficiency of enzyme NADPH oxidase Chronic Granulomatous

Disease.
Catalase Negative organisms produce hydrogen peroxide used by
myeloperoxidase of the host to kill it
Infection with Catalase positive bacteria
Synthesis of NO. (NADPH is a coenzyme Arginine from Citrulline
Mitochondrial system:
Conversion of cholesterol to steroid
Bile acid synthesis
Hydroxylation of vitamin D.
Microsomal system: liver
Detoxification of drugs, carcinogens, petroleum products, pesticides etc.
Q. A 19-year-old, African American male military recruit is about to be sent to Iraq on
his assignment. In preparation for his tour of duty, he is given a prophylactic dose of
primaquine to prevent malaria. Several days after he begins taking the drug, he
develops fatigue and hemolytic anemia. Which of the following proteins is likely
deficient?
Glucose -6- phosphatase
Glucose 6-phosphate dehydrogenase
Aldolase B
Muscle phosphorylase
Pyruvate kinase
Q.Chronic granulomatous Disease is a condition where the macrophages cannot kill
the bacteria with the help of oxygen mediated respiratory burst due to deficiency of
which of the following enzymes?
Glucose-6-PO4 dehydrogenase
NADPH Oxidase
Glutathione peroxidase
Peroxidase
Catalase
Fructose and Galactose metabolism, Uronic acid pathway
URONIC ACID IS REQUIRED FOR :A. Synthesis of GAGs Synthesis of Glycoproteins and
Proteoglycans
B. Conjugation of Bilirubin and Drugs
L-xylulose reductase- blocked in pentosuria
Phosphorylation to fructose -1- phosphate by enzyme fructokinase in liver. (not
dependent on insulin)
extra hepatic tissues: glucose competes with fructose for hexokinase.
Muscle which contains only hexokinase phosphorylates fructose to F6P which is a
direct glycolytic intermediate.
Fructokinase bypass PFk-1
Fructokinase is blocked in essential fructosuria (excretion in urine, no other
diagnosis) avoid fructose

14

Aldolase B blocked in Hereditary Fructose Intolerance (build up of phosphate-F1-P)

lead to liver failure, hypoglycemia, hyperuricemia,
the liver failure lead to hypoglycemia because no glycogen phosphorylase and decreased
ATP also Depletion of ATP.AMP rises and in absence of inorganic Pi , AMP is destroyed
Hyperuricemia
Prolonged fructose ingestion in infants leads to poor feeding, vomiting, hepatomegaly,
jaundice, hemorrhage, proximalrenaltubule syndrome (fanconi like syndrome)
Aldolase B is present in liver, kidney and small intestine converts fructose 1-P into DHAP
and glyceraldehyde 3P.
-increased rate of lipogenesis( fatty acid and triglyceride synthesis) in liver as a result of
Acetyl CoA and glycerol-3-PO4 accumulation formed by the more rapid fructose
metabolism then glycolysis due to the bypass of pfk-1
Can get fructose from glucose through aldose reductase and sorbitol
If you have diabetes, chill on the glucose because Hyperglycemia (as in diabetes)
results in elevated levels of intracellular glucose in lens, nerve, kidney. This leads to
water retention in these tissues due to osmotic effects of sorbitol swelling,
cataract, peripheral neuropathy and vascular problems nephropathy and
retinopathy as complications of diabetes
AGEs-advanced glycated end product= glycated protein in plasma, they also attach
to receptors=capillaries increase in thickness=attachment to AGE receptor=activation
of NFKB
Galactose Metabolism:
fxn=energy converts to glucose, (synthesis of lactose, synthesis of GAG, glycoprotein
and proteoglycan these all require UDP Galactose)
Galactokinase deficiency = Non classical galactosemia (just cataracts)
Galactose 1-phosphate uridyl transferase deficiency= Classical galactosemia
(worse)Galactosemia, Galactosuria, vomiting, Diarrhoea, jaundice,
cataract formation (elevated galactitol
Liver damage- cirrhosis and brain damage - mental retardation
Accumulation would inhibit the production of the second messenger
inositol in the signalling system and hence causing a mental retardation.
Q. A newborn vomits after each feeding of milk based formula and does not gain
weight. Biochemical testing reveals a severe def of Galactose-1-phosphate uridyl
transferase. If this condition goes untreated, which of the following is the likely
outcome for this patient?
Benign disease except for cataract formation
Chronic emphysema appearing in early adulthood
Chronic renal failure appearing in adolescence

15

Mental retardation and later death in infancy

Gastrointestinal symptoms that remit with puberty
Q.A 4-month-old infant is brought to emergency clinic by the parents in an
unconscious state. The mother complains that the child has had repeated
attacks of unconsciousness, especially in the night, in the past few
months. On examination, the child had massive Hepatomegaly.
Biochemical tests revealed that the blood glucose level was 40mg/dL. The
lactate and triglyceride and uric acid levels in circulation were increased.
Urine did not contain any reducing sugar. The developmental milestones
of the child were normal; however, the weight gain of the infant was poor.
Administration of glucagon failed to increase the blood glucose level.
What is the most probable biochemical defect?
Von Gierke disease
Classical Galactosemia
Hereditary fructose intolerance
Essential Fructosuria
Medium chain acyl Co-A dehydrogenase deficiency
Glycogen metabolism
In health, liver glycogen maintain blood glucose level particularly between meals whereas
muscle glycogen is a readily available source of glucose in the exercising muscles.
Glucose 6-phosphatase is absent in muscle-so NO contribution to plasma glucose
level by muscle glycogen-only locally available glucose 6-P for glycolysis and HMP shunt
Glycogen synthase (regulated by insulin) in liver and muscle (Glut4)- can only elongate
existing chains (alpha 1-4 linkage)
branching enzyme- also known as glucosyl 4:6 transferase OR amylo [14] [16]transglucosidase an alpha (1-6 linkage)
Glucagon turns off glycogen synthase
Pyrophosphate - is hydrolyzed to inorganic phosphate by Pyrophosphatase and thus
ensures the IRREVERSIBILITY of glycogen synthase.
Glycogen acts a primer as well, but if theres no glycogen you can use GLYCOGENIN
(16) glucosidase activity free glucose released.
Glycogen storage diseases
Type 1: Von Gierkes Dx= def. in glucose 6 phosphatase hyperuricemia due to
increase glucose 6 phosphate
Type 2: Pompes= Lysosomal 14 and 16 glucosidase (acid maltase)
(heart failure by 2)(cardiomegaly- normal blood glucose)

16

Type 3: Limit dextrinosis, Forbe's or Cori's disease- Liver and muscle

debranching enzyme is deficient, accumulation of characteristic branched
polysaccharide (limit dextrin)
Type 4: Amylopectinosis, Andersen's disease- branching enzymeaccumulation of amylopectin like polysaccharide with few branch points
Type 5: Myophosphorlylase deficiency, McArdle's syndrome, muscle phosphorylase
deficiency - poor exercise tolerance
Type 6: Hers dx- liver phosphorylase
Type 7: Tarui's disease- def in Muscle and erythrocyte PFK 1
Q. 6-month-old who is failing to thrive is brought to your clinic. Tests reveal
hepatosplenomegaly, muscle weakness and atrophy, hypotonia, and decreased deep tendon
reflexes. Blood tests reveal that the infant has normal glucose levels. Biopsy of the liver reveals
initial stages of cirrhosis due to the accumulation of an abnormal glycogen with few branch
points, whose structure resembles amylopectin. The clinical and laboratory results presented
are indicative of which glycogen storage disease?
Von Gierke disease
Tarui disease
Andersen disease
Cori or Forbes disease
McArdle disease
Q. An infant with growth retardation, hepatomegaly and hypoglycemia demonstrate hepatic
fibrosis without fat accumulation on liver biopsy. There is also accumulation of small chain
dextrin- like material within the cytosol of the hepatocytes. Which of the following enzymes is
most likely deficient in this patient?
Glucose -6-phosphate
Glycogen phosphorylase
Debranching enzyme
Amylo- (1,6) glucosidase
Pyruvate kinase.
Q.After a meal, blood glucose enters cells and is stored as glycogen, particularly in the liver.
Which of the following is the donor of new glucose molecules in glycogen?

17

UDP-glucose-1-phosphate
UDP-glucose
UDP-glucose-6-phosphate
Glucose-6-phosphate
Glucose-1-phosphate
Regulation of blood glucose level
Glucose is the only fuel that will supply energy to skeletal muscle under anaerobic
conditions.
Glucagon Binds To Specific Receptors In Hepatic Cell Plasma Membrane , And
This Activates Adenylyl Cyclase Through a G Protein Linked Mechanism.
The c-AMP generated activates PHOSPHORYLASE and enhances rate of
glycogen degradation while inhibiting glycogen synthase .
Glucagon has no effect on glycogenolysis in muscle.
Its a potent lipolytic agent also. It increases adipose tissue c-AMP levels and
this activates the hormone sensitive lipase which breaks down TAG to FA
+Glycerol.
It also enhances gluconeogenesis
Epinephrine promotes glucagon
Insulin structure is kept together by disulphide bond
Insulin receptor-tyrosine receptor
Q. Which of the following substances will BE elevated in a starving cell?
A. 5AMP
B. c-AMP
C. ATP
D. GTP
E. glucose
Q. Which of the following statements correctly describe human glucose
metabolism?
A. Liver is impermeable to glucose in the absence of insulin

18

B. Pancreatic -cells, liver and brain are freely permeable to glucose due to specific
glucose transporters
C. Liver glucokinase phosphorylates glucose at high rates under all conditions
D. Extrahepatic tissues are permeable to glucose when glucagon is present
E. Liver takes up glucose when serum glucose is normal but releases it when serum
glucose is high
Hemoglobin
Biosynthesis of heme: Succinyl CoA( FROM TCA CYCLE)
2)AA - GLYCINE
need B6 for ALA Synthase- rate limiting step
2/3 rd of TOTAL HEME SYNTHESIZED GOES FOR SYNTHESIS OF cytP450
apo-repressor= negative feed back for heme
Most common is PORPHYRIA is AIP
ALA Synthase- Sideroblastic anemia
ALA Dehydrogetase- inhibited by lead (ferrotchelase)
Uroporphyrinogen synthase/ deaminase 1: AIP
Uroporphyrinogen synthase 3: Congenital erythropoietic (Gunthers)- first time
you see photo sensitivity
Uroporphyrinogen decarboxylase: cutanea tarda

DRUGS that gives you porphryin :- Certain medicines, such as

BARBITURATES(SEDATIVE ) , GRISEOFULVIN (ANTI-FUNGAL)birth control pills,
antibiotics, and medicines for treating seizures.
Why ? THEY ARE METABOLISED BY CYT P450 , hence UTILIZATION of HEME in
CYTOCHROME P450 IS INCREASED .This DECREASES THE INTRACELLULAR
CONCENTRATION.
Q. AIP is the major autosomal-dominant acute hepatic porphyria. This
disease is caused by a deficiency in porphobilinogen (PBG) deaminase, an
enzyme of heme biosynthesis. Patients afflicted with this disease would be
expected to excrete excess amounts of which of the following?

(A) Delta-aminolevulinic acid (ALA)

19

(B) Coproporphyrinogen III

(C) Hydroxymethylbilane
(D) Protoporphyrin IX
(E) Type III uroporphyrinogen
skin blistering, prefer to work at night: Uroporphyrinogen decarboxylasecutanea tarda
lives in an 80 years old house- ALA dehydratase
Q. A 25-year-old man has experienced chronic blistering and scarring of his skin
when exposed to sunlight. This man is a smoker and drinks heavily, both of which
exacerbate his responses to sunlight. Analysis of his urine and plasma indicates a
high accumulation of complex porphyrins, predominantly uroporphyrin.The symptoms
and clinical signs displayed by this patient indicate he is suffering from which of the
following disorders?

(A) Acute intermittent porphyria (AIP)

(B) Hereditary coproporphyria (HCP)
(C) Porphyria cutanea tarda (PCT) decarboxylase
(D) Variegate porphyria
(E) X-linked sideroblastic anemia
Catabolism of HEME: ENZYME :- Glucuronosyltransferase
Q. An infant with severe jaundice that is not corrected by phototherapy is in danger of
developing kernicterus. This can occur in infants with CriglerNajjar syndrome, a genetic
disorder in which there is a near-complete deficiency of glucuronyl transferase. Which of the
following laboratory findings would be expected in blood tests in an infant with Crigler
Najjar syndrome?
Decreased hematocrit
Decreased indirect bilirubin
Increased direct bilirubin
Increased indirect bilirubin
Increased reticulocyte count
Chemistry of hemoglobin
Like water (polar and charged): lysine (+), arginine (+), aspartate (-) and glutamate (-)

20

polar: serine, threonine, asparagine, glutamine, histidine

and
tyrosine
hydrophobic: alanine, valine, leucine, isoleucine, proline, phenylalanine,
tryptophan, cysteine, and methionine
Q, What type of amino acids will be present in the core? Valine, arginine or glutamic acid ?
Porphyrins are pyrrole rings joined together by methenyl bridges (=HC-)bridges.
4 nitrogens, 2 02, and a histidine
Proximal histidine binds iron to heme, distal histidine stabilize O2 after iron binds
Binding sites: Oxygen and carbon monoxide Fe2+
Carbon-di-oxide amino terminal end of globins.
H+ ions histidine 146 of beta subunit.
hemoglobin abnormality that decrease P50 for hemoglobin for 26 to 20 mmHg=
polycythemia, decreased p50, increased affinity
carbon monoxide poisoning=cherry red blood, higher affinity
Methemoglobin (Fe3+)= chocolate brown blood
-use NADH and cytochrome B5 reductase together to reduce it or NADPH and methylene
blue. since you need NAPH then you need G6PD or pyrivate kinase for NADH
Globin chain goes through splicing to make the hemoglobin
Sickle Cell: Mutation : is replaced by valine at 6th position of Beta chain.
Hb S is less soluble in acidosis and dehydration
However at acidic pH (citrate buffer)HbS moves faster than Hb A
Alpha thalassemia-gene deletions
Beta thalassemia- decrease (frontal bossing), hair on end
Q. An Asian child has severe anemia with prominence of the forehead (frontal bossing)
and cheeks. The red cell hemoglobin concentration is dramatically decreased, and it
contains only beta-globin chains with virtual deficiency of alpha-globin chains. Which of the
following mechanisms is the most likely explanation?
A. A transcription factor regulating the alpha-globin gene is mutated
B. A regulatory sequence element has been mutated adjacent to an alpha-globin gene
C. A transcription factor regulating the beta-globin gene is mutated
D. A transcription factor regulating the alpha and beta -globin genes is deficient
E. A deletion has occurred surrounding an alpha-globin gene
Q, HbC disease is caused by a single amino acid substitution (lysine instead of Glutamic
acid) at position 6 in the bete-globin chain of the hemoglobin molecule. Patients

21

homozygous for HbC have a mild chronic hemolytic anemia. HbS disease generally
causes a more severe condition compared to HbC disease because HbS disease:
A. Impairs oxygen binding to the heme moiety
B. Impairs proper folding of the alpha-helix in the beta-globin chain
C. Allows hydrophobic interaction among hemoglobin molecules
D. Impairs beta-globin interaction with 2,3-bisphosphoglycerate
E. Stabilizes iron moiety at ferric state (fe3+).
Q. An infant to a greek immigrant appears healthy at birth but develops transfusion
dependent hemolytic anemia by the age of 6 months. his erythrocytes contain insoluble
aggregates of hemoglobin subunits. The child developed normally in utero because at that
time he produced high quantities of:
Alpha globin
B. Beta globin
C. Gamma globin
D. Delta globin
E. Epsilon globin
Biosynthesis of fatty acids
Q. Which of the following substances will be elevated in a cell following a
high fatty meal ?
A. c AMP
B. 5 AMP
C. ADP
D.GDP
E. glucagon
LIPIDS:
Biosynthesis of FA
Substrates of fatty acid synthesis:
Acetyl Co-A
NADPH
ATP
Biotin
HCO3 source of CO2.
Steps of fatty acid synthesis
1.Transport of acetyl Co-A to cytosol
2. Synthesis of Palmitate from acetyl CO-A
3. Elongation of Palmitate to increase the length of fatty acid

22

4. Desaturase system to produce unsaturated fatty acids.

Sources of NADPH: HMP pathway, MALIC enzyme (Malate to Pyruvate), Cytosolic
Isocitrate dehydrogenase (cytosolic reducing equivalents (NADH) produced during
glycolysis contribute to the reduction of NADP+ to NADPH needed for palmitoyl CoA
synthesis.
From cytosol to inner mitochondrial membrane require ATP-citrate lyase
~once there acetyl CoA is converted to Malonyl CoA through Acetyl Coa carboxylase
(require biotin) rate limiting step and is activated by citrate
Q. Acetyl CoA is produced in mitochondria .Fatty acid synthesis occurs in cytosol
.Which of the following enzyme is responsible for regeneration of acetyl CoA in
cytosol for this process ?
A. Acetyl CoA carboxylase
B. PDH
C.Isocitrate dehydrogenase
D. Citrate synthase
E. ATP citrate lyase
Since glycerol kinase is activity is low in adipose tissue, the source of glycerol 3 p is
by DHAP from glycolysis using glycerol 3P dehydrogenase
Lipolysis requires the presence of epinephrine , norepinephrine, glucagon,
adrenocorticotropic hormone (ACTH), -and -melanocyte stimulating hormones ,
Thyroid stimulating hormone (TSH), Growth Hormone (GH ) , and vasopressin.
Many of these activate Hormone sensitive Lipase.
This is done by increasing the concentration of c-AMP either by stimulating the
enzyme adenylyl cyclase or by inhibiting the enzyme Phosphodiesterase.
Glucocorticoids can stimulate HSL directly.
Leptin is a product of the Ob gene.
Leptin acts on receptors in the hypothalamus of the brain where it inhibits appetite
Eicosanoids:
Dietary linoleic acid- from plants
Phospholipase lipase A2- cortisol inhibits, epinephrine and thrombin activated
Aspirin-inhibited COX
COX 1- constitutive form
COX 2- mediate inflammatory response
PGI2 (Prostacyclins)- vasodilation, inhibit platelet aggregation
PGF2 -stimulates uterine contraction & has role in LH- induced ovulation
bronchoconstrictor
PGE2- bronchodilator, inflammation, fever

23

PGE2 especially in adipose tissue decreases c-AMP and inhibits Lipolysis.

PGE2 also increases calcium mobilization from bone and glycogen synthesis.
PGs increase gastric motility
Thromboxane promote platelet aggregation
Induce labor (abortion) = PGE2 and PGF2A
PGE2= erectile dysfunction
The physiological actions of PGI3 and TXA3 are shifted in favor of prevention of
blood clotting
COX -2 inhibitors :Celecoxib, Rofecoxib
Q. A 58-year-old woman is undergoing a myocardial infarct and is given 162 mg of
aspirin, owing to the cardioprotective effects of aspirin during such an incident.
Aspirin is a nonsteroidal anti-inflammatory drug that inhibits cyclooxygenase.
Cyclooxygenase is required for which one of the following conversions?
(A) Thromboxanes from arachidonic acid
(B) Leukotrienes from arachidonic acid
(C) Phospholipids from arachidonic acid
(D) Arachidonic acid from linoleic acid
(E) HPETEs and subsequently hydroxyeicosatetraenoic acids (HETEs) from
arachidonic acid
Q. The cardioprotective effects of aspirin occur due to the inhibition of the
synthesis of which one of the following?
(A) PGF2
(B) PGE2
(C) TXA2
(D) PGA2
(E) PGI2
Q. A 40-year-old woman has rheumatoid arthritis, a crippling disease causing severe
pain and deformation in the joints of the fingers. She is prescribed prednisone, a
steroid that exerts its beneficial effects through anti-inflammatory pathways. What
is the mechanism of steroidal anti-inflammatory agents?
(A) Prevent conversion of arachidonic acid to epoxides
(B) Inhibit phospholipase A2
(C) Promote activation of prostacyclins
(D) Degrade thromboxanes
(E) Promote leukotriene formation from HPETEs
Lipid Transport:

24

Apolipoproteins: C2 for lipoprotein lipase

A1 for Lecithin cholesterol acyl transferase
ligands (receptor): Apo B100 and APO E LDL receptor
APO A1 HDL
APO B48 Chylomicrons
APO -B100 VLDL, IDL, LDL
APO C and E present in all particles(with exceptions ) predominantly donated by
HDL
LDL- highest cholesterol
Lipoprotein lipase- activated by insulin and co-factor apo C-II
Hypercholesterolemia or Familial Hypercholesterolemia- No cholesterol can come inside,
no LDL receptors (atherosclerosis)
Abetalipoproteinemia :- No chylomicrons , VLDL, LDL, mutation in gene (MTP)
Familial alpha lipoprotein deficiency
Drugs used in Hyperlipoproteinemia: Statins - HMG-CoA reductase inhibitors
Q. A lipoprotein synthesized in liver , containing high concentration of TG and mainly
cleared from circulation by adipose tissue and muscle ?
CHYLOMICRONS
HDL
IDL
LDL
VLDL
Q. Which of the following lipoproteins increase in Familial hypercholesterolemia Type
1.
A. Chylomicrons
B. LDL
C. VLDL
D. Total cholesterol
E. IDL
Type I = increase chylomicrons
Type II =increased LDL
Lipid Chemistry
Fatty acid are never free, always bound to albumin
Saturated= no double bonds
Even number- e.g.-Palmitic acid / hexadecanoic acid , stearic

25

acid.
Odd number e.g.-Propionic acid, Valeric acid
Trans-fat is harmful. Trans fat not broken by LIPASE- Body cant metabolize it -desaturase
Dipalmitoyl phosphatidyl choline acts as a surfactant in lungs. Reduces surface tension
of alveoli
If its absence respiratory distress syndrome.
Gangliosides Cerebrosides + Sialic acid (9 carbon sugar NANA).
Lysosomal enzymes:
Gangliosides: hexoaminidase: Tay Sachs (no hepatosplenomegaly) cherry red
Cerebrosides: - Galactosidase ( FABRYS)
- Galactosidase (krabbes )
- Glucosidase (Gauchers)(Glucocerebrosidase )
Sphingomyelin: Sphingomyelinase: Niemann Picks disease
Q. A two year old boy is brought to the OPD with hepatosplenomegal and mental
retardation. He is also having erosion of long bones. A liver biopsy showed accumulation
of glucosylseramide in liver cells. The abnormality lies in which of the following enzymes ?
Hexosaminidase A
Arylsulfatase A
Sphingomyelinase
Beta-glucosidase
Alpha galactosidase
Q. 5A one-year-old baby presents with increasing flaccid paralysis, lack
of coordination, and hyporeflexia. Over the next several years, the
child's condition deteriorates to a bedridden vegetative state.
Funduscopic examination reveals optic atrophy. Extensive
enzymological
studies document a deficiency of arylsulfatase A (cerebroside
sulfatase)
in leukocytes. Which of the following is the most likely diagnosis?
A. Gaucher's disease
B. Krabbe's disease
C. Metachromatic leukodystrophy
D. Niemann-Pick disease
E. Tay-Sachs disease MC
Oxidation of fatty acids and ketogenesis
Hormone sensitive lipase: break down of triglycerides to FA and glycerol
Glycerol to Glycerol Po4 to glucose (gluconeogenesis) through glucokinase
FA to Acetyl CoA to liver

26

Increased fatty acid oxidation is a characteristic of starvation and of diabetes mellitus,

leading to ketone body production by the liver (ketosis). Ketone bodies are acidic and
when produced in excess over long periods, as in diabetes, cause ketoacidosis, which is
ultimately fatal.
Gluconeogenesis is dependent upon fatty acid oxidation, any impairment in fatty acid
oxidation leads to hypoglycemia.
Alpha oxidation- occurs in peroxisomes (branched chained FA)
Beta oxidation- in mitochondria (long and medium FA) and in peroxisomes (VLCFA)
Omega oxidation- occurs only when mitochondria doesnt oxidize MCFA
(accumulation of dicarboxylic acids adipic (C6), suberic (C8), sebacic (C10).
Profound Hypoglycemia no ATPs for running gluconeogenesis.
Absent ketone bodies in the blood why ? no acetyl Co-A
Hyperammonemia - octanoic acid mitochondrial poison coma.
Common cause of sudden infant death syndrome (SIDS)
Dicarboxylic aciduria and presence of medium chain acyl carnitines in urine
Step 1 : Activation of fatty acids (Acyl CoA synthetase) only step that require
ATP
2: CPT-1 moves acyl-Coa inside= rate limiting step
3. Carnitine-acylcarnitine translocase- acylcarnitine is transported into the
matrix in exchange for free carnitine
4. CPT-II transfer of acyl group from carnitine to CoA in the mitochondrial
matrix regenerating free carnitine
Insulin upregulate Acyl Coa carboxy
Oxidation of fatty acid with odd no. of carbon atom yields acetyl CoA + Propionyl
CoA( Enters TCA as Succinyl Co-A).Thus this portion of odd chain fatty is glucogenic.
Methylmalonic aciduria
Deficiency of vitamin B12 accumulation of methyl malonyl Co-A.
Mutation in methyl malonyl Co-A mutase
Oxidation of fats need the help of Oxaloacetate which enters into the cycle and is
regenerated in the end .
Impaired oxidation of fatty acids gives rise to diseases associated with nonketotic
hypoglycemia .
MCAD:
Most common inborn error of fatty acid metabolism
Defect in first step of beta oxidation

27

Present in milk seen in infants dependent on mothers milk.

Accumulation of medium chain fatty acids.
Jamaica Vomiting dx
Unripe Ackee fruit Hypoglycin
Inactivates medium and short chain acyl Co-A dehydrogenase.
Dicarboxylic aciduria due to omega oxidation.
Zellweger Syndrome: peroxisomal disorder
Q. A 4-month-old infant presents with a seizure. His mother reports that her infant
has been irritable and lethargic over the past several days. The infant is found to be
profoundly hypoglycemic and have low ketones . Short-chain dicarboxylic acids are
found to be elevated in the serum. The most likely enzyme deficiency is which of the
following?
(A) Medium-chain acyl CoA dehydrogenase (MCAD)
(B) Carnitine acyltransferase I
(C) Hormone-sensitive lipase
(D) Pyruvate carboxylase
(E) Fatty acyl CoA synthetase
Refsums disease is a rare neurologic disorder caused by accumulation of phytanic
acid formed from Phytol , a constituent of chlorophyll .
Susceptible people have a deficiency of phytanoyl-CoA hydroxylase that prevents
-oxidation .
Q. What is the primary role of carnitine in fatty acid oxidation ?
(A) Activates long-chain fatty acids in the cytosol
(B) Transport of acyl groups across the inner mitochondrial membrane
(C) Is converted to enoyl CoA
(D) Is converted to -hydroxyacyl CoA
(E) Is involved in breakdown of even-chain, but not odd-chain, fatty acids
Q. An infant is born with a high forehead, abnormal eye folds, and deformed ear
lobes and shows little muscle tone and movement. After multiple tests, he is
diagnosed with Zellweger syndrome, a disorder caused by peroxisome
malformation. What type of fatty acid would you expect to accumulate in patients
with Zellweger syndrome?
(A) Short-chain fatty acids
(B) Acetyl CoA
(C) Dicarboxylic acids

28

(D) Long-chain fatty acids

(E) Very-long-chain fatty acids
Ketogenesis/ Ketolysis:
Ketogenesis Occurs When There Is a High Rate of Fatty Acid Oxidation in the Liver
Liver can only synthesize ketone bodies but it cannot utilize them.
Only extrahepatic tissues can utilize acetoacetate because of the enzyme
Succinyl-CoA-acetoacetate transferase (THIOPHORASE).
HMG CoA Synthase= rate limiting step of ketogenesis
DKA: Kussumals breathing: metabolic acidosis., Fruity odour acetone
Q. A 12-year-old boy presents with fatigue, polydipsia, polyuria, and polyphagia. A
fingerstick glucose measurement shows a glucose level of 350mg/dL in his serum.
He is diagnosed with type 1 diabetes mellitus, a disease characterized by a
deficiency of insulin. Which one of the following is most likely occurring in this
patient?
A) Increased fatty acid synthesis from glucose in liver
B) Decreased conversion of fatty acids to ketone bodies
C) Increased stores of Triacylglycerol in adipose tissue
D) Increased production of acetone
E) Chronic pancreatitis
Biosynthesis
ofonly
cholesterol
Cholesterol
excreted
through
BILE
Rate Whats
limitingisrequired?
step=
HMG
CoA
reductase
Acetyl
CoA
from
Glycolysis,
ATP
and
NADPH
(from the
pathways)
Need to know Farnesyl diphosphate gives
you Co Q
and
dolichol
(important
for3 synthesis
of glycoproteins)
Person complains after statin drug, they have Rhabdomyolysis, give Co Q pills
Statin drugs inhibit HMG Reductase so no mevalonate
Bile acid regulation require 7 alpha hydroxylase (need vit C)- rate limiting step
Requires O2, NADPH, cytochrome P450
Q. Why are dietary fibers mainly helpful in decreasing cholesterol?
A. They promote the GI motility and decrease cholesterol absorption.
B. They are not digested and they dont produce Acetyl CoA upon metabolism
C. They cause a fullness of stomach and decrease appetite
D. They bind to bile salts and decreases their reabsorption
E. They decrease cholesterol absorption from gut

29

Q.The anticholesterolemic action of simvastatin is based on its effectiveness as a

competitive inhibitor of rate-limiting enzyme in cholesterol biosynthesis. The reaction
product normally produced by this enzyme is
A. Squalene
B.Methylmalonate
C.Lanosterol
D.Mevalonate
E.acetoacetate
Q. Which of the following substances is decreased if HMG CoA reductase inhibitors
are used for treatment of hypercholesterolemia?
A. Acetyl Co A
B. Malonyl CoA
C. CoQ
D. Succinyl CoA
E. ATP
Molecular Biology
B-DNA is physically stable
Topoisomerase and Gyrases removes super coils
Histones: Arginine and lysine
90% of chromosomes dont code: Constitutive heterochromatin(densely packed )
mRNA: Contains the genetic code for protein synthesis. It is the copy of
DNA derived after transcription
5 end has 7-methyl Guanosine triphosphate CAP
Polyadenylate tail 20 to 30 residues
Hn RNA is converted to m-RNA by by snRNA
tRNA: Acceptor arm ends with CCA nucleotides
aminoacid specific
Anticodon arm - three base region that can base pair to the corresponding three base codon
region on mRNA.
D-arm recognition site for the enzyme aminoacyl t-rna synthase.
T arm recognition site for ribosome to attach
Fxn of mRNA to ribosomes: 16s identifies Shine Dalgarno sequence in Prokaryotes
18s identifies Kozak consenses sequence in Eukaryotes
Nucleolus- rRNA
A sample of human DNA is subjected to increasing temperature until the major fraction exhibits
optical density changes due to disruption of its helix (melting or denaturation). A smaller
fraction is atypical in that it requires a much higher temperature for melting. This smaller,
atypical fraction of DNA must contain a higher content of
a. Adenine plus cytosine

30

b. Cytosine plus guanine

c. Adenine plus thymine
d. Cytosine plus thymine
e. Adenine plus guanine
Q.In a given sample the amount of adenine nucleotide is 20%. Calculate the amount of cytosine
content in DNA?
20%
30%
40%
50%
60%
Q. During a laboratory experiment a scientist finds that one DNA strand contains 10 As,
12Gs, 14 Cs and 14 Ts. How many of each base is found in the complete double stranded
molecule.
A. A = 26, G = 22, C=22, T=26
B. A=20, G =22, C=22, T=20
C. A=24, G = 26, C=26, T=24
D. A=10, G =12, C=14, T=14
E. A=26, G=24, C=24, T=26
Q, Histones can bind DNA tightly as they have a positive charge. This is due to the amino
acid
A. aspartate
B. glycine
C. lysine
D. proline
E. tyrosine
DNA Replication:
DNA synthesizing enzymes are called DNA polymerases
Since eukaryotes take so long to synthesis DNA replication initiates at many
different sites simultaneously. origin of replications
Prokaryotes- have DNA polymerase I,II,III Eukaryotes have DNA polymerase alpha
and delta
Telomerase have reverse transcriptase
Quinolones and Fluoroquinolones inhibit DNA gyrase
Q. The activity of which DNA polymerase is critical for determining accuracy of nuclear
DNA replication?

31

a. 5 to 3 polymerase activity of DNA polymerase

b. 5 to 3 exonuclease activity of DNA polymerase
c. polymerase activity of DNA polymerase II
d. 3 to 5 exonuclease activity of DNA polymerase
e. Primase activity of DNA polymerase III
Q, The anti- Peudomonas action of Norfloxacin is due to inhibition of which enzyme
of DNA replicaton?
A) DNA polymerase I
B) topoisomerase II
C) DNA ligase
D) DNA Polymerase II
E) RNAaseH
Q. It is well known that DNA polymerases synthesize DNA only in the 5 to 3 direction. Yet,
at the replication fork, both strands of parental DNA are being replicated with the synthesis
of new DNA. How is it possible that while one strand is being synthesized in the 5 to 3
direction, the other strand appears to be synthesized in the 3 to 5 direction? This
apparent paradox is explained by
a. 3 to 5 DNA repair enzymes
b. 3 to 5 DNA polymerase
c. Okazaki fragments
d. Replication and immediate crossover of the leading strand
e. Lack of RNA primer on one of the strands
Q, Given that the chromosomes of mammalian cells may be 20 times as large as those of
Escherichia coli, how can replication of mammalian chromosomes be carried out in just a
few minutes?
a, Eukaryotic DNA polymerases are extraordinarily fast compared with prokaryotic
polymerases
b. The higher temperature of mammalian cells allows for an exponentially higher
replication rate
c. Hundreds of replication forks work simultaneously on each piece of
chromosomal DNA
d. A great many different RNA polymerases carry out replication simultaneously on
chromosomal DNA
e. The presence of histones speeds up the rate of chromosomal DNA replication

32

DNA Repair Mechanism:

Mismatch repair: An enzyme called as the DAM methylase methylates DNA at N6
position for all adenines within 5 GATC sequences. Newly synthesized strands are
not methylated immediately. This allows to distinguish b/w the two. HNPCC
hereditary non polyposis colon cancer (LYNCH syndrome).Autosomal Dominant:
hMSH-2 gene or hMLH1
Base excision repair: Identified by DNA glycosylase and removed. The attached
sugar and phosphate are removed by Apurinic or Apyrimidinic endonucleases.
Nucleotide excision repair: Excision endonuclease (exinuclease), Defect in nucleotide
excision repair (XPA and XPC) gene
Double stranded break repair: Ku protein and DNA dependent protein kinase are involved
in repair.
Bloom Syndrome: BLM gene
Ataxia telengiectasia: Defect in the ATM gene
Q. Patients with hereditary nonpolyposis colon cancer [HNPCC(114500)] have genes with
microsatellite instability, that is, many regions containing abnormal, small loops of unpaired DNA.
This is a result of a mutation affecting
a. Mismatch repair
b. Chain break repair
c. Base excision repair
d. Depurination repair
e. Nucleotide excision repair
Q. Following ultraviolet damage of DNA in skin
a. A specific excinuclease detects damaged areas
b. Purine dimers are formed
c. Both strands are cleaved
d. Endonuclease removes the strand
e. DNA hydrolysis does not occur
Q. Following ultraviolet damage of DNA in skin
a. A specific excinuclease detects damaged areas
b. Purine dimers are formed

33

c. Both strands are cleaved

d. Endonuclease removes the strand
e. DNA hydrolysis does not occur
Q. Dyskeratosis congenital is a genetic condition with impaired proliferation of stem
cells. The defect has been traced to an inadequate production of an enzyme required
for chromosome duplication in nuclei of dividing cells. This enzyme contains a single
stranded RNA.What is the deficient enzyme?
A) DNA POLYMEASE
B)DNA LIGASE
C)PRIMASE
D)TELOMERASE
E)DNA POLYMERASE
G1/S check point= Cyclin E/CDK-2= dissociate phospate from Rb/p53
MDM-2 regulates p53 by feedback.
Recombinant DNA:
PCR: Produces virtually unlimited copies of a very small DNA sample
Requirements:
Taq polymerase (DNA polymerase)
d-NTPs
Specific primers
Buffer
Magnesium chloride
DNA template
the problem with PCR: Both introns and exons will be present. Collect mRNA of a particular gene and then synthesize C-DNA by using reverse transcriptase.
Restriction endonucleases: Restriction endonucleases hydrolyze phosphodiester
linkages in both the strands of DNA at highly specific sites. They recognize
palindromes in 5 3 direction on both the strands. Sticky blunt ends that ligase will
work on.
The sticky ends= can go back together so homopolymer will be added
HIV- Western blot
Gene therapy: Human DNA is synthesized and it integrates into HOST CELL DNA
Gene Regulation:

34

Chaperones are heat shock proteins preventing aggregation

Ubiquitin- a tag for proteasomes, I=cell
Operon- promoter region
Operator- binding site for proteins
Histone acetylation and deacetylation: addition of acetyl groups to
histones disruption of nucleosome and DNA separation
Q, The bacterial lac operon is controlled by both glucose and lactose levels. Which of the
following conditions would result in the greatest level of transcription from the lac operon?
Both glucose and lactose present
Glucose present but no lactose
Lactose present but no glucose
No glucose or lactose present
Q. The lac operon is negatively controlled by the lactose repressor and positively
controlled by which of the following?
Increased concentrations of glucose and cyclic AMP (cAMP)
Decreased concentrations of glucose and cAMP
Increased concentrations of glucose, decreased concentration of cAMP
Decreased concentrations of glucose, increased concentration of cAMP
Increased concentrations of glucose and adenosine triphosphate (ATP)
Q. A culture of E. coli is grown in a medium containing glucose and lactose. The
expression of the lactose operon over time in the cells is shown in the graph below.
Which statement best describes the change that occurred at point A?
Lactose was added to the culture
cAMP concentration increased in the cells
Glucose was added to the culture
Repressor protein dissociated from the operator
Repressor protein became bound to the
Transcription:
The enzyme responsible for the RNA synthesis is DNA-dependent RNA
polymerase.
Rifampicin=inhibit the RNA synthesis.
The mushroom Amanita phalloides (The Death Cap Mushroom) produces a toxin
called alpha-amanitin which is a potent inhibitor of RNA polymerase II.
RNA pol I = 45S RNA

35

RNA II = hnRNA
RNA III = 5S RNA, tRNA, snRNA
The promoter is the DNA sequence that RNA-pol can bind
The prokaryotic RNA-pol can bind to the DNA template directly in the transcription
process.
The eukaryotic RNA-pol requires co-factors to bind to the DNA template together in
the transcription process.
The first nucleotide on RNA transcript is always purine triphosphate.
transcription initiation complex. =pppGpN-OH, DNA, RNA polymerase
Prokaryotes have Shine Delgarno
Modification includes
Capping at the 5- end ( CO-TRANSCRIPTIONAL)
Tailing at the 3- end(POST TRANSCRIPTIONAL)
mRNA splicing(POST TRANSCRIPTIONAL) (use a lariat)
RNA editing (POST TRANSCRIPTIONAL)
Q, During Rna synthesis, the DNA template sequence TAGC would be transcribed to
produce which of the following sequences?
ATGC
GCTA
CGTA
AUCG
GCUA The answer is E. RNA is antiparallel and complementary to the template
strand
Q, Which of the following most correctly describes mammalian messenger RNAs?
A. They are usually transcribed from both DNA strands
B. They are normally double-stranded
C. Their content of uridine equals their content of adenine
D. They have an overall negative charge at neutral pH
E. Their ratio of ribose to purine bases equals 1

Translation: (cytoplasm)
Prokaryotes= odd, 30,50,70
Eukaryotes = even 40,60,80
stop codons (UAA, UAG, UGA).

36

mRNA = initiation requirements: the small and large ribosomal subunits

mRNA
GTP
charged initiator tRNA
initiation factors
m-RNA is read from 5 3 end.
m-RNA is identified by 18 s RNA through 7 methyl guanosine CAP
Phosphorylated eIF-2 binds tightly to and inhibits eIF-2 which is
required for regeneration of GTP from GDP on factor 2
Insulin increases protein synthesis by removing the phosphate and
inactivating eIF-2a
cap independent translatinal initiation=elF-4G
Nontranslating mRNAs Can Form Ribonucleoprotein Particles that Accumulate in
Cytoplasmic Organelles Termed P Bodies
Drugs inhibiting 30s subunit: Streptomycin (aminoglycosides) interfering
with
binding of formyl met-tRNA to P site and initiation of protein synthesis.
Tetracyclins: binds to 16s rRNA. Prevent binding of aminoacyl t-RNA to A site.
50S= Linezolid : prevents the formation of the initiation complex,
composed of the 30S and 50S subunits of the ribosome, tRNA, and mRNA.
Chloramphenicol binds to 50 s subunit. Inhibits peptidyl transferase
activity of 23s rRNA.
Macrolides (Erythromycin) binds to P site and prevents ribosomal
translocation.
The anticodon of yeast serinyl-tRNA is 5-AGC-3. Which of the following is
most likely to be a serine codon?
5-ACG-3
5-CCG-3
5-GCU-3
5-UAG-3
5-UCG-3
Aromatic aminoacid metabolism:
~BIosynthesis of non essential amino acids
-need transamination and some need B6
*Cysteine synthesis starts from Methionine

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Phenylalanine essential
Tyrosine non essential
Tryptophan essential
Phenylalanine to tyrosine require phenylalanine hydroxylase
Tyrosine to DOPA require Dihydrobiopterin reductase
DOPA to dopamine require B6
Dopamine to NE require Cu+
NE to E require S- Adenosyl Methionine (SAM)
From E to Metanephrine require MAO/COMT then VMA is made
Schizophrenia Dopamine overproduction
Parkinsons disease : Damage to Nigro-striatal tract - dec. Dopamine
Treatment: Levo-DOPA + Carbidopa
Pheochromocytoma (epinephrine excess ) or Neuroblastoma-Excess of VMA in urine
Melanin is made from tyrosine
Catabolism of phenylalanine and tyrosine
~phenyl alanine hydroxylase= PKU
tyrosine aminotransferase= tyrosinemia II (Keratosis of palmar surface)
homogentiste= alkaptonuria
Fumaryl acetoacetate hydrolase= tyrosinemia I (cabbage like odor)
If the route from phenylalanine to tryosine is blocked, it will be converted to Phenyl
acetyl Glutamine
Melatonin synthesis
From tryptophan to Serotonin to Melatonin= require folate and B6 and SAM
MAO-A inhibitors (Anti-Depressants)= keeps serotonin to make person feel
good
Q. A patient presents with headaches, palpitations, nausea and vomiting and
elevated blood pressure. These symptoms appear after the person has eaten a large
meal containing aged cheeses and wine. The patients history indicates that he is on
some medicaton for a different condition. Assuming that the medication is in some
way involved in these symptoms, which enzyme might be the target of this drug?
Glutamate decarboxylase
Monoamine oxidase
Tyrosine hydroxylase

38

DOPA decarboxylase
COMT (catechol O-methyl transferase)

Tryptophan Metabolism: gives you niacin and acetoacetyl Co-A

Carcinoid syndrome :- (Argentaffinomas )
Diagnosis : HIAA in urine
Pellagra like synptoms : Def of B6 or
Diarrhoea, Dementia and Dermatitis
Remember Hartnups disease
Melatonin: promotes sleep sleep wake cycle
Q. The non essential amino acid that becomes essential in PKU is :A. Phenylanaline
B.Tyrosine
C.Tryptophan
D. ALANINE
E. Cysteine
Q. The cause of light skin color in PKU is
A. decreased synthesis of melanin from Phe
B. decreased synthesis of melanin from Tyr
C. excess melanin synthesis from Phe
D. excess of phenylketones
E.mental retardation causes decreased melatonin

Branched Chained AA
Leucine uses Isovaleryl Co-A dehydrogenase def gives a cheesey
odor
Isoleucine uses Propionyl Co-A carboxylase
Valine uses Methylmalonyl Co-A mutase
Maple Syrup DX: Def of enzyme Alpha ketoacid decarboxylase
/dehydrogenase
Amino Acid and Protein Chemistry:
Glycine - inhibitory, smallest
Leucine-ketogenic

39

Sulphur containing- methionine and cysteine

Basic(polar)= arginine. lysine and histidine
OH groups: Serine, threonine, tyrosine
Arginine and histidine= semiessential
First class proteins: - They contain all essential a.a. in required proportion for ideal
body growth and development. E.g egg albumin , milk casein
Q, Several complexes in the mitochondrial ETC contain non-heme iron tightly bound
to a thiol group of which amino acid?
A. Glutamine
B.Methionine
C.Tyrosine
D.Cysteine
E.Serine
Collagen Structural defects:
Osreogenesis imperfecta COL1A1: type 1 collagen dx
Ehlers Danlos Syndrome= type 3 collagen defect (distensible +hypermoble joints)
Alport=Ty[re 4 basement membrane
Fuch corneal= type 8 defect
Menkes dx= ATP7A gene, decreased Cu because no lysl oxidase
Goodpasture: Produces IgG antibodies against Alpha-3 chain of type 4
Type IV collagen
Marfan= fibrillin
Alpha 1- Antitrypsin= SERPINA
Pseudoxantoma elastic=ABCC6 gene
Q. A 4 month old infant who failed to grow and appeared to be mentally retarded was
brought to the clinic for testing .The physician noted that the infant had abnormally
kinky and hypopigmented hair. Arteriograms showed tortuosity of the major arteries.
Blood test showed that the infant had low serum ceruloplasmin and only 10% of normal
copper levels.
What is the clinical disorder?
1)Osteogenesis imperfecta
2)Scurvy
3) Menkes disease
4)Blue baby syndrome
5)Phenylketonuria

40

abundant terminal disulfide bonds= due to impaired extracellular cleavage.

defect of elastin-associated glycoprotein = Marfans Syndrome
Collagen and elastin:
~in collagen formation, Hydroxylation of proline and lysine
Requires a dioxygenase with Fe . (Vit C keeps the iron reduced )
Cross links formed by lysyl/prolyl oxidase
~In elastin, cross links involve Lys and alLys lysyl oxidase
4 Lys can be cross-linked into desmosine
Desmosines account for elastic properties
Matrix metalloproteinases= degrade elastin

Keratin =properties depend strongly on the degree of disulfide cross-linking.

Q. A culture of fibroblast cells is provided with equal all the 20 amino acids.
After 10 days , the concentration of the amino acids is assessed .Which
amino acid will have the lowest concentration?
A. Lysine
B.methionine
C.Glycine
D.proline
E.Cysteine
Q. Elastin fibres in the alveolar walls of the lungs can be stretched easily during inspiration
and recoil to their original shape once the force is released. This process facilitates
expiration. The property described can be best explained by:
Heavy posttranslational hydroxylation
High content of polar amino acids
Chain assembly to form a triple helix
Interchain crosslinks involving lysine
Abundant interchain disulfide bridges
Q. A 14-year old male presents to your office complaining of easy bruising.
Physical examination reveals soft and loose skin as well as multiple
ecchymoses in the forearm and pretibial regions. Histologic evaluation
with electron microscopy shows collagen fibrils that are abnormally thin
and irregular. Which of the following stages of collagen synthesis is most
likely impaired in this patient?

41

RNA signal sequence recognition

Amino acid incorporation into polypeptide chain
Triple helix formation
Lysine residue hydroxylation
cleavage of propeptides
Sulfur containing basic AA
Oxidation of fatty acid with odd no. of carbon atom yields acetyl CoA +
Propionyl CoA( Enters TCA as Succinyl Co-A).Thus this portion of odd
chain fatty is glucogenic.
Cystinuria: defect in renal and intestinal absorption of COLA , will have
cystine stones
Cystinosis- lysosomal disorder= Defective carrier mediated transport of
cysteine
Marfan= Lens dislocation is upwards and outwards
Aortic incompetance / valvular heart disease
Mental retardation absent
Congenital homocysteinuria= Lens dislocation is downwards and inwards
Ischemic heart disease due to thromboembolic
phenomenon
Mental retardation common
Acquired homocysteinuria = Vitamin deficiencies B6= increased homocycteine,
increased methionine
B12 +FOLATE def. is dec methionine but in homocysteine
No Marfanoid habitus
Diff btw folate and vit b12 but vit b12 deficiency you get methmalonic
aciduria
Metabolism of histidine
~ FIGLU= measure in folate acid deficiency
histidemia: Diagnosis: sweat urocanate levels decreased
FIGLU excretion decreased.
Arginine=urea, creatine phosphate, creatinine, NO
Glycine=Formation of Heme: first step, Formation of Glutathione,
Formation of Bile salts Glycocholic acid , Conjugation Hippuric acid
(Hippuric acid), C4, C5, N7 of Purine Ring formation

42

From glycine to glyoxalate = need B6 and Alanine glyoxylate

Aminotransferase
def in Alanine glyoxylate Aminotransferase= Primary hyperoxaluria
-1
def in glyoxylate reductase= Primary hyperoxaluria-2C
Causes for increased oxalate stones:
Green leafy vegetables oxalates
Ascorbic acid Vit C
Ethylene glycol poisoning antifreeze
Primary oxaluria Type 1 and 2
~~~~all leading to oxalate stone formation renal obstruction
Formation of Creatine and Creatinine: require SAM and Creatine Phospho
KInase
Q. A 56 year old man is being evaluated for macrocytic anaemia. He was
severely malnourished.Both homocysteine and methyl malonate were
elevated in his blood and urine , and the transketolase level in his RBC was
low.
What is the best evidence cited that the anaemia is due to B12 deficiency?
A. Macrocytic anaemia
B. Elevated methyl malonate
C. elevated homocysteine
D. decreased homocysteine
E. severe malnutrition
Q. If there is B12 deficiency , which other conditions could develop in such
a patient ?
A.peripheral neuropathy
B. Gout
C. Wernickes Korsakoffs syndrome
D. Destructon of parietal cells
E. Bleeding from gums
Q. A 49 year old man has ectopia lentis and comes to ER with deep vein
thrombosis .He has a normal hematocrit and RBCs are normocytic normochromic.
A mutation of genes coding for which of the following is the cause ?
A. Cystathionine synthase
B. Homocysteine methyl transferase (thrombolytic :remember!)
C.Fibrillin

43

D.Lysyl oxidase]
E. FACTOR VIII
Q, Amino acid analysis of this patients plasma would most likely reveal an
abnormally elevated level of
A. Lysine
B.Leucine
C. methionine
D. Ornithine
E. Cysteine
Urea Cycle and its defects:
Nitrogen balance: positive= more ingested than lost
negative= more lost than ingested
Ammonia toxicity= Flapping Tremor (Asterixis)
( Correlate flapping tremor later on with Liver failure in Clinical
medicine )
Slurred Speech
Blurred Vision
COMA Death
Fate of ammonia: Glutamate and Glutamine are involved in recycling of
amino acids.
Nitrogen part is toxic. Urea Neutral molecule Non toxic ( 80-85%)
High protein diet lead to activation of NAG which activated CPS-1 in the
motochondria
Hyperammonemia type -1: Autosomal recessive, Defect in CPS- 1,
No orotic aciduria
Hyperammonemia type-2: X-linked recessive, Defect in OTC,
orotic aciduria is present, spills into pyrimidine synthesis
3. Citrullinemia :
Defect in arginosuccinate synthase
Citrullinuria
Autosomal recessive
4. Arginosuccinic aciduria:
Defect in arginosuccinate lyase
Arginosuccinic acid blood, CSF, Urine

44

5. Hyperargininemia :
Diet without arginine
Defect in arginase enzyme
Q. The first reaction in the degradation of the majority of common
amino acids involves participation of :
NAD +
Pyridoxal Phosphate
Thiamine Pyrophosphate(TPP)
FAD
NAD and TPP
Q. After thorough investigations a man is diagnosed with orotic
aciduria . To find out the cause of orotic aciduria which of the
following investigations will you prefer?
A. ALP levels
B. vitamin b12 assay
C. FIGLU excretion assay
D. Peripheral smear
E. serum bilirubin
Nucleotide Metabolism
Hydroxyurea- ribonucleotide reductase
5-flurouracil- Thymidylate synthesis

Dihydrofolate reductase- methrotrexate for eukaryotes, trimethoprim

r2x04mghl
CPS-!= in mitochondria, uses free ammonia as a source of nitrogen, activated
NAG, in urea synthesis
CPS-II= in cytosol, uses glutamine as a source of nitrogen, activated by
PRPP, involved in pyrimidine synthesis
Orotic aciduria= have megaloblastic anemia due to folate defeciency that
unresponsive to vit B12 and folate, give uridine
UTP is feedback inhibitor of CPS II
Q. A one year old female child is weak and anemic. The child was found to
have megaloblastic anemia. The height and weight of the child are
less than normal. Urine demonstrates an elevated level of orotic acid
excretion and normal blood ammonia levels.

45

Which of the following enzyme will be deficient ?

A. Ornithine transcarbamoylase
B. Orotate Phosphoribosyl transferase
Purine Synthesis:
PRPP Amidotransferase: inhibited by Allopurinol, 6- Mercaptopurine,
Azathioprine
Purine Catabolism:
SCID= def. in ADENOSINE DEAMINASE, def in both T and B cells
Allopurinol also inhibit Xanthine oxidase, so no uric acid
HGPRT deficiency- Lesch Nyan (no salvage pathway so excess uric acid and
gout)
Treatment of Gout: Colchicine inhibits migration of inflammatory cells
NSAIDS Antiiflammatory and analgesics
Xanthine oxidase inhibitors Allopurinol.
Q. Gout is characterized by elevated uric acid concentrations in blood and
urine due to a variety of metabolic abnormalities that lead to the
overproduction of purine nucleotides. Allopurinol is used in the treatment
of gout because this drug, and its metabolic product, alloxanthine, act as
inhibitors of:
a)
b)
c)
d)
e)

Xanthine Oxidase
PRPP synthetase
Adenyl succinate synthase
Hypoxhantine guanine phosphoribosyl transferase
Nucleotides

Hereditary Orotic aciduria is characterized by severe anemia, growth

retardation, and high levels of orotic acid excretion. It is produced by
deficit of enzymes related with:
a)
b)
c)
d)
e)
f)

synthesis of pyrimidine nucleotides

catabolism of pyrimidine nucleotides
synthesis of purine nucleotides
catabolism of purine nucleotides
synthesis of Heme
catabolism of Heme

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