1

ANTI RETROVIRAL THERAPY:

Thymidine analogues: Guanosine analogues:
– zidovudine (AZT) - abacavir (ABC)
– Stavudine (d4T) - entecavir (ETV)
Cytidine analogues: Adenosine analogues:
– zalcitabine (ddC) - didanosine (ddI)
– lamivudine (3TC) - tenofovir (TDF) {NtRTI}
– emtricitabine (FTC) - adefovir (ADV) {NtRTI}

Mitochondrial inherited disorders:

a) Diabetes mellitus and deafness(DAD)
b) Leber's hereditary optic neuropathy (LHON)
c) Leigh syndrome, subacute sclerosing encephalopathy
d) Neuropathy, ataxia, retinitis pigmentosa, and ptosis (NARP)
e) Myoneurogenic gastrointestinal encephalopathy (MNGIE)
f) Myoclonic Epilepsy with Ragged Red Fibers (MERRF)
g) Mitochondrial myopathy, encephalomyopathy, lactic acidosis, stroke-like symptoms (MELAS)
h) Chronic Progressive External Opthalmoplegia (CPEO)
i) Kearns-Sayre Syndrome (KSS)
j) Pearson syndrome
k) Infantile Myopathy & Lactic acidosis (fatal & non-fatal forms)
2
 3

Purine synthesis:
4
 5

Lesch Nyhan Syndrome

Nibbled lips & finger Teeth marks on hands

 6

Pyrimidine Synthesis:
 7

Classes of Proteins Involved in Replication

Protein Function

DNA polymerases Deoxynucleotide polymerization

Helicases Processive unwinding of DNA
Topoisomerases Relieve torsional strain that results from helicase-
induced unwinding
DNA primase Initiates synthesis of RNA primers

Single-strand binding proteins Prevent premature reannealing of dsDNA

DNA ligase Seals the single strand nick between the nascent
chain and Okazaki fragments on lagging strand

A Comparison of Prokaryotic and Eukaryotic DNA Polymerases

E coli Eukaryotic Function

I Gap filling following DNA replication, repair, and

recombination
II DNA proofreading and repair
β DNA repair
γ Mitochondrial DNA synthesis
III ε Processive, leading strand synthesis
DnaG α Primase
δ Processive, lagging strand synthesis
8
 9

Lac operon model

lacZ encodes β-galactosidase

lacY encodes a permease
lacA encodes a thiogalactoside transacetylase
lacI encodes the lac operon repressor protein.
 10

Michaelis Menton Eq The Lineweaver Burk plot Eq

Rate Determining Enzymes of Metabolic Processes:

PROCESS ENZYME

Glycolysis Phosphofructokinase-1 (PFK-1)

Gluconeogenesis Fructose-1,6-bisphosphatase

TCA cycle Isocitrate dehydrogenase

Glycogenesis Glycogen synthase

Glycogenolysis Glycogen phosphorylase

HMP shunt Glucose-6-phosphate dehydrogenase (G6PD)

De novo pyrimidine synthesis Carbamoyl phosphate synthetase II

De novo purine synthesis Glutamine-phosphoribosylpyrophosphate (PRPP) amidotransferase

Urea cycle Carbamoyl phosphate synthetase I

Fatty acid synthesis Acetyl-CoA carboxylase (ACC)

Fatty acid oxidation Carnitine acyltransferase I

Ketogenesis HMG-CoA synthase

Cholesterol synthesis HMG-CoA reductase

Other Plots
Name Remarks
Eadie Hofstee plot vi versus vi/[S]
Hanes-Woolf plot [S]/vi versus [S]
Hills equation Enzymes with cooperative binding
Dixon plot Determining inhibition constants.
To evaluate the comparative potency of competitive inhibitors.
 11

Lineweaver Burk Plot for different types of reversible inhibitors:

Competitive Non Competitive Un Competitve

Km Increased No change Decreased

Vmax No change Decreased Decreased

 12

Irreversible Inhibitors:

Three types:
• Group specific reagents. E.g. DIPF, acts on chymotrypsin and acetylcholinesterase

• Reactive substrate analogs (also called affinity labels). E.g. TPCK, acts on
chymotrypsin; 3-bromoacetol phosphate, acts on triose phosphate isomerase (TPI)

• Suicide inhibitors (mechanism based inhibitors). E.g. N,N-dimethylpropargylamine,

acts on monoamine oxidase (MAO); penicillin, acts on Glycopeptide transpeptidase.

Enzyme levels after MI

Enzyme Detectable Peak Normalisation
CK-MB 3-6 hrs 12-24 hrs 2-3 days
AST 6-8 hrs 24-36 hrs 4-6 days
LDH 8-10 hrs 48-72 hrs 7-10 days

Seperation of proteins
i. On the basis of solubility: Precipitation by heavy metals, salting out: globulins are
precipitated at half saturation while albumin is precipitated at full saturation with NH4Cl.
ii. On the basis of molecular size:
a. Dialysis
b. Gel filtration chromatography
c. Ultra centrifugation
iii. On the basis of molecular charge:
a. Ion exchange chromatography
b. HPLC
c. Electrophoresis
d. PAGE: seperation is based on sieving effects plus electrophoretic mobility
e. SDS-PAGE:
i. Sodium dodecyl sulphate is a strong detergent
ii. SDS imparts large negative charge to the protein
iii. Proteins are denatured
iv. Denatured proteins assume rod like shape
v. Proteins have similar shapes and charge to mass ratio
vi. Seperation takes place on the basis of molecular mass
f. Isoelectric focussing
iv. On the basis of affinity binding:
a. Affinity chromatography
b. Precipitation by antibodies
 13

Collagen:

Types of Collagen and Their Genes

Type Genes Tissue
I COL1A1, COL1A2 Most connective tissues, including bone
II COL2A1 Cartilage, vitreous humor
III COL3A1 Extensible connective tissues such as skin, lung, and the
vascular system
IV COL4A1–COL4A6 Basement membranes
V COL5A1–COL5A3 Minor component in tissues containing collagen I
VI COL6A1–COL6A3 Most connective tissues
VII COL7A1 Anchoring fibrils
VIII COL8A1–COL8A2 Endothelium, other tissues
 14

Urea Cycle:
 15

Branched Chain Organic Acidurias/ Acidemias:

• Maple Syrup Urine Disease
• Isovaleric Aciduria
• Propionic Aciduria
• Methylmalonic Aciduria
• Methylcrotonyl Glycinuria
• Methylglutaconic Aciduria
• Short-/Branched-chain Acyl-CoA Dehydrogenase Deficiency
• Methyl-3-Hydroxybutyryl-CoA Dehydrogenase Deficiency
• Isobutyryl-CoA Dehydrogenase Deficiency
• Hydroxyisobutyric Aciduria
• Malonic Aciduria
 16

A. Elevated Amounts of Unconjugated Bilirubin in Blood:

1. Hemolytic Anemias
2. Neonatal "Physiologic Jaundice“
3. Crigler–Najjar Syndrome, Type I; Congenital Nonhemolytic Jaundice
4. Crigler–Najjar Syndrome, Type II
5. Gilbert Syndrome
6. Lucey–Driscoll syndrome
7. Toxic Hyperbilirubinemia
B. Conjugated Hyperbilirubinemia:
1. Obstruction of the Biliary Tree
2. Dubin–Johnson Syndrome
3. Rotor Syndrome
 17

Alpha Bilirubin: Unconjugated bilirubin is also called alpha Bilirubin.

Beta Bilirubin: Bilirubin monoglucuronide.
Gamma Bilirubin: Bilirubin diglucuronide.
Delta Bilirubin: Bilirubin attached to albumin covalently; has increased half life;
responsible for persistence of elevated serum bilirubin levels in chronic pathologies, even after
treatment of underlying defect.

Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are
usually markedly elevated in hepatitis, whereas serum levels of alkaline phosphatase are
elevated in obstructive liver disease.
 18

Table A. Summary of Major Findings in the Porphyrias

Enzyme Involved Type & Class Major Signs and Results of Laboratory
Symptoms Tests
1. ALA synthase X-linked Anemia Red cell counts and
(erythroid form) sideroblastic hemoglobin decreased
anemia3
(erythropoietic)
2. ALA dehydratase ALA dehydratase Abdominal pain, Urinary ALA and
deficiency (hepatic) neuropsychiatric coproporphyrin III
symptoms increased
3. Uroporphyrinogen I Acute intermittent Abdominal pain, Urinary ALA and PBG
synthase4 porphyria (hepatic) neuropsychiatric increased
symptoms
4. Uroporphyrinogen Congenital Photosensitivity Urinary, fecal, and red
III synthase erythropoietic cell uroporphyrin I
(erythropoietic) increased
5. Uroporphyrinogen Porphyria cutanea Photosensitivity Urinary uroporphyrin I
decarboxylase tarda (hepatic) increased
6. Hereditary Photosensitivity, Urinary ALA, PBG, and
Coproporphyrinogen coproporphyria abdominal pain, coproporphyrin III and
oxidase (hepatic) neuropsychiatric fecal coproporphyrin III
symptoms increased
7. Protoporphyrinogen Variegate porphyria Photosensitivity, Urinary ALA, PBG, and
oxidase (hepatic) abdominal pain, coproporphyrin III and
neuropsychiatric fecal protoporphyrin IX
symptoms increased
8. Ferrochelatase Protoporphyria Photosensitivity Fecal and red cell
(erythropoietic) protoporphyrin IX
increased
 19

Distribution of Glycosaminoglycans
GAG Sugars Location
Hyaluronic Acid GIcNAc, D-glucuronic Synovial fluid, vitreous humor, loose connective tissue
acid (GlcUA)
Chondroitin Sulphate GaINAc, GlcUA Cartilage, bone, cornea
Keratan Sulphate I GlcNAc, Gal Cornea
Keratan Sulphate II GlcNAc, Gal Loose connective tissue
Heparin D-glucosamine (GlcN), Mast cells
L-iduronic acid (IdUA)
Heparan sulfate GlcN, GlcUA Skin fibroblasts, aortic wall
Dermatan sulfate GalNAc, IdUA, (GlcUA) Wide distribution

MUCOPOLYSACCHARIDOSES
Name Alternative Enzymatic Defect Urinary Metabolites
Designation
Hurler, Scheie, MPS I-H, I-S, α-L-Iduronidase Dermatan sulfate, heparan
Hurler-Scheie I-HS sulfate
Hunter MPS II Iduronate sulfatase Dermatan sulfate, heparan
sulfate
Sanfilippo A MPS III-A Heparan sulfate N-sulfatase Heparan sulfate
(sulfamidase)
Sanfilippo B MPS III-B α-N-Acetylglucosaminidase Heparan sulfate
Sanfilippo C MPS III-C α-Glucosaminide N- Heparan sulfate
acetyltransferase
Sanfilippo D MPS III-D N-Acetylglucosamine 6-sulfatase Heparan sulfate
Morquio A MPS IV-A Galactosamine 6-sulfatase Keratan sulfate,
chondroitin 6-sulfate
Morquio B MPS IV-B β-Galactosidase Keratan sulfate

Maroteaux- MPS VI N-Acetylgalactosamine 4-sulfatase Dermatan sulfate

Lamy (arylsulfatase B)
Sly MPS VII β-Glucuronidase Dermatan sulfate, heparan
sulfate, chondroitin 4-
sulfate, chondroitin 6-
sulfate
 20

 Fibroblasts, leukocytes, tissues, amniotic fluid cells, or serum can be used for the assay of many
of the above enzymes.
 Clinical findings include cloudy corneas, mental retardation, stiff joints, cardiac abnormalities,
hepatosplenomegaly, and short stature.
 The term MPS V is no longer used.
 The existence of MPS VIII (suspected glucosamine 6-sulfatase deficiency) has not been
confirmed.
 At least one case of hyaluronidase deficiency (MPS IX) has been reported.

 Pyruvate Dehydrogenase Complex::

• Enzymes:
– Pyruvate Dehydrogenase (E1)
– Dihydrolipoyl Transacetylase (E2)
– Dihydrolipoyl dehydrogenase
• Co-Enzymes:
– TPP
– FAD
– NAD
– CoASH
– Lipoate
Major Glucose Transporters

Tissue Location Functions

Facilitative bidirectional transporters
GLUT 1 Brain, kidney, colon, placenta, Glucose uptake, basal transport
erythrocytes
GLUT 2 Liver, pancreatic cell, small intestine, Rapid uptake or release of glucose
kidney
GLUT 3 Brain, kidney, placenta Glucose uptake, lowest Km
GLUT 4 Heart and skeletal muscle, adipose tissue Insulin-stimulated glucose uptake
GLUT 5 Small intestine Absorption of glucose, fructose
Sodium-dependent unidirectional transporter
SGLT 1 Small intestine and kidney Active uptake of glucose against a
concentration gradient
 21

Glycolysis:
 22

Rapoport-Luebering shunt:
 23

Kreb’s/ TCA/ Citric acid

Cycle:
 24

Involvement of the citric acid cycle in transamination and gluconeogenesis:

The bold arrows indicate the main pathway of gluconeogenesis.

 25

Glycogen Metabolism:
 26

Glycogen Storage Diseases

Type Name Enzyme Deficiency
0 — Glycogen synthase
Ia Von Gierke's disease Glucose 6-phosphatase
Ib — Endoplasmic reticulum glucose 6-phosphate transporter
II Pompe's disease Lysosomal 14 and 16 glucosidase (acid maltase)
IIIa Limit dextrinosis, Forbe's or Liver and muscle debranching enzyme
Cori's disease
IIIb Limit dextrinosis Liver debranching enzyme
IV Amylopectinosis, Andersen's Branching enzyme
disease
V Myophosphorlylase deficiency, Muscle phosphorylase
McArdle's syndrome
VI Hers' disease Liver phosphorylase
VII Tarui's disease Muscle and erythrocyte phosphofructokinase 1
 27

HMP Shunt/ Pentose Phosphate Pathway:

 28

Electron Transport Chain (ETC):

 29

Inhibitors of ETC:
 Complex I:
 Pericidin A
 Amobarbital
 Amytal
 Rotenone
 Secobarbital
 Chlorpromazine
 Guanethidine
 Demerol
 Complex II:
 Malonate
 Carboxin
 TTFA (2-Thenoyltrifluoroacetone)
 Complex III:
 BAL
 Antimycin A
 Phenformin
 Complex IV:
 Hydrogen sulphide
 Carbon monoxide
 Cyanide
 Azide
 Complex V (ATP synthase complex):
 Inhibitors of Fo:
 Oligomycin
 DCCD (Dicyclohexylcarbodiimide)
 Venturicidin (also known as Aabomycin)
 Inhibitors of F1:
 Tentoxin
 Efrapeptin
 Inhibitors of ATP-ADP translocase:
 Atractyloside
Uncouplers:
 Exogenous
 2,4-Dinitrophenol
 Dicumarol
 FCCP (carbonyl cyanide-p-trifluorocarbonyl-cyanide methoxyphenyl hydrazone)
 Endogenous:
 via UCP-1
 Thermogenin
 Via UCP-3
 Thyroxine
 Norepinephrine
 Epinephrine
 Leptin
 Via UCP-4
 Essential fatty acid deficiency
 Purine nucleotides
 30

Classification of lipids:
1. SIMPLE LIPIDS: Esters of fatty acids with various alcohols.
a. Fats: Esters of fatty acids with glycerol. Oils are fats in the liquid state.
b. Waxes: Esters of fatty acids with higher molecular weight monohydric alcohols.
2. COMPLEX LIPIDS: Esters of fatty acids containing groups in addition to an alcohol and a fatty
acid.
a. Phospholipids: Lipids containing, in addition to fatty acids and an alcohol, a phosphoric
acid residue. Phospholipids may be regarded as derivatives of phosphatidic acid, in
which the phosphate is esterified with the —OH of a suitable alcohol.
i. Glycerophospholipids: The alcohol is glycerol, examples include:
 Phosphatidylcholines (Lecithins):
a. The most abundant phospholipids of the cell membrane.
b. Dipalmitoyl lecithin is a very effective surface-active agent and
a major constituent of the surfactant preventing adherence, due
to surface tension, of the inner surfaces of the lungs. Its absence
from the lungs of premature infants causes respiratory distress
syndrome.
 Phosphatidylethanolamine (cephalin):
a. Ethanolamine replaces choline.
b. Also found in cell membranes.
 Phosphatidylserine:
a. Also found in cell membranes.
b. Plays a role in apoptosis (programmed cell death).
 Phosphatidylinositol:
a. The inositol is present as the stereoisomer, myoinositol.
b. Is a precursor of second messengers.
c. Phosphatidylinositol 4, 5-bisphosphate upon stimulation by a
suitable hormone agonist, is cleaved into diacylglycerol and
inositol tris-phosphate, both of which act as internal signals or
second messengers.
 31

 Cardiolipin:
a. Phosphatidic acid + Phosphatidic acid + Glycerol
(diphosphatidylglycerol).
b. Found only in mitochondria and is essential for the
mitochondrial function.
c. Decreased cardiolipin levels or alterations in its structure or
metabolism cause mitochondrial dysfunction in conditions
including:
i. Aging
ii. Heart failure
iii. Hypothyroidism
iv. Barth syndrome (cardioskeletal myopathy).
 Lysophospholipids:
a. Phosphoacylglycerols containing only one acyl radical, for
example, lysophosphatidylcholine (lysolecithin).
b. Found in oxidized lipoproteins and has been implicated in some
of their effects in promoting atherosclerosis.
 Plasmalogens:
a. Occur in brain & muscle.
b. Resemble phosphatidylethanolamine but possess an ether link on
the sn-1 carbon instead of the ester link found in acylglycerols.
c. Typically, the alkyl radical is an unsaturated alcohol.

i. Sphingophospholipids: The alcohol is a complex amino alcohol, sphingosine, e.g.,

i. Sphingomyelins:
– Found in large quantities in brain and nerve tissue.
– On hydrolysis, the sphingomyelins yield a fatty acid, phosphoric acid,
choline, and, sphingosine.
– No glycerol is present.

b. Glycolipids (glycosphingolipids): Lipids containing a fatty acid, sphingosine, and

carbohydrate.
– Widely distributed in every tissue of the body, particularly in nervous tissue such
as brain.
– Occur in the outer leaflet of the plasma membrane.
– Major glycolipids found in animal tissues are glycosphingolipids, which contain
the basic structure ceramide, (sphingosine + fatty acid) plus one or more sugars.
i. Cerebrosides: Ceramide and a monosaccharide.
– Galactosylceramide is a major glycosphingolipid of brain and other
nervous tissue, found in relatively low amounts elsewhere.
– Glucosylceramide is the predominant simple glycosphingolipid of
extraneural tissues, also occurring in the brain in small amounts.
ii. Sulfatides: Ceramide and a sulphated monosaccharide.
– Present in high amounts in myelin.
iii. Globosides: Ceramide and an oligosaccharide.
iv. Gangliosides: Ceramide and an oligosaccharide with at least one sialic acid
residue.
– Neuraminic acid is the principal sialic acid found in human tissues.
– Gangliosides are also present in nervous tissues in high concentration, where
they appear to have receptor and other functions.
 32

– Ganglioside are labelled as per number of sialic acid residues:

a. GM: Ganglioside with one sialic acid residue.
b. GD: Ganglioside with two sialic acid residues.
c. GT: Ganglioside with three sialic acid residues.
d. GQ: Ganglioside with four sialic acid residues.
Ganglioside subgroups are further classified as per electrophoretic patterns, e.g., GM1, GM2, and
GM3, based on distance moved on electrophoresis.
– The simplest ganglioside found in tissues is GM3, which contains ceramide,
one molecule of glucose, one molecule of galactose, and one molecule of
NeuAc.
– GM1, a more complex ganglioside derived from GM3, is known to be the
receptor in human intestine for cholera toxin.

Sphingolipidoses:

Disease Enzyme Deficiency Clinical Symptoms

Tay-Sachs disease Hexosaminidase A Mental retardation, blindness, muscular

weakness
Fabry’s disease α-Galactosidase Skin rash, kidney failure (full symptoms only
in males; X-linked recessive)
Metachromatic Arylsulfatase A Mental retardation and psychologic
leukodystrophy disturbances in adults; demyelination
Krabbe’s disease β-Galactosidase Mental retardation; myelin almost absent
Gaucher’s disease β-Glucosidase Enlarged liver and spleen, erosion of long
bones, mental retardation in infants
Niemann-Pick disease Sphingomyelinase Enlarged liver and spleen, mental
retardation; fatal in early life
Farber’s disease Ceramidase Hoarseness, dermatitis, skeletal
deformation, mental retardation; fatal in
early life
33
34
 35

Ketogenesis:

Fatty acids
W3 family W6 family W7 family W9
Alpha linolenic Gamma linolenic Palmitoleic Oleic
Timnodonic Arachidonic Eladic
Cervonic Linoleic
 36

Lipoprotein structure:

Composition of lipoproteins in plasma of humans

Lipoprotein Source Main lipid Apolipoproteins
components
Chylomicron Intestine Triacylglycerol A-I, A-II, A-IV, B-48, C-
I, C-II, C-III, E
Chylomicron Chylomicron Triacylglycerol, B-48, E
remnants phospholipids,
cholesterol
VLDL Liver Triacylglycerol B-100, C-I, C-II, C-III
IDL VLDL Triacylglycerol, B-100, E
cholesterol
LDL VLDL cholesterol B-100
HDL Liver, intestine, Phospholipids, A-I, A-II, A-IV, C-I, C-II,
chylomicron, VLDL cholesterol C-III, D, E
Pre-β HDL A-I
Albumin/free fatty Adipose tissue Free fatty acids
acids
37
 38

Generic Classification Increased Lipoprotein Increased Lipid

TYPE
I Lipoprotein lipase Chylomicrons Triacylglycerols
deficiency
IIa Hypercholesterolemia LDL Cholesterol
(LDL receptor deficiency)
IIb Combined hyperlipidemia LDL, VLDL Triacylglycerols, cholesterol
III Dysbetalipoproteinemia IDL Triacylglycerols, cholesterol
IV Hypertriglyceridemia VLDL Triacylglycerols
V Mixed hyperlipidemia VLDL, chylomicrons Triacylglycerols
 39

Urinary Odours:

Tests for different amino acids

Analyte Test Colour
Proteins with more than Biuret test Violet
one peptide bond
Phenylalanine, tyrosine, Xanthoproteic test Yellow
tryptophan
Tyrosine Milon’s test Red
Tryptophan Aldehyde test Violet ring
Arginine Sakaguchi test Bright Red
Cysteine, Cystine Sulphur test, Nitroprusside test Black
Pauly’s test Histidine Cherry red
All aminoacids Ninhydrin Rheuman purple. Proline &
hydroxyproline give yellow colour
 40

Tests for carbohydrates

Analyte Test Colour
All carbohydrates Molisch’s test Brown ring
Polysaccharides Iodine test Blue with starch, red with glycogen
Monosaccharides Barfoed’s test Red ppt
Ketose sugar Seliwanoff’s test Cherry red
Reducing sugars Benedict’s test Brick red ppt
Osazone test: Glucose: needle shaped crystals
Galactose: needle shaped crystals
Lactose: cotton ball/ pin cushion shaped
Maltose: sunflower shaped
Tests for abnormal constituents of urine
Analyte Name of test Colour
Reducing sugar Benedicts Brick red ppt
Protein Heat coagulation test White
Heller’s test White/ Yellow ring
Esbach test Yellow ppt
Ketone bodies Rothera’s test Purple ring
Nitroprusside test Red colour
Bile salts Hay’s surface tension/ sulphur test
Bile pigments Gmelin’s test Multicoloured ring
Fouchet’s test Green ppt

Sample collection and agent used:

Purpose of blood collection Preferred anticoagulant
TLC, DLC, Hb estimation EDTA
Blood Glucose estimation Potassium oxalate-NaF
LFT, KFT, Lipid profile, Enzyme assays in serum No anticoagulant
Blood grouping Trisodium citrate
DNA isolation EDTA
Blood gas analysis Heparin

Vitamins and major catalytic role:

Coenzymes Transferred entities
Biotin Carbon dioxide
Coenzyme A Acyl group
FAD (flavin adenine dinucleotide) Hydrogen atoms
NAD (nicotinamide adenine dinucleotide.) Hydride ion (H-)
Pyridoxal phosphate Amino groups
Tetrahydrofolate One carbon groups (other than CO2)
Thiamine pyrophosphate Hydroxy-ethyl
Coenzyme B12 Alkyl groups or hydrogen atoms
 41

• Required (in form of Pyridoxal phosphate) as a cofactor for :

– Transamination
– Deamination
– Decarboxylation
– Catecholamines, serotonin, GABA
– Serine (Serine racemase)
– Methionine, cysteine ( cystathionine synthase and cystathionase)
– Selenium
– Tryptophan to Niacin
– Glycogenolysis
– Sphingolipids
– Heme synthesis

Conditions associated with a monoclonal increase in the γ-region are as follows:

 Multiple myeloma
 Smoldering myeloma
 Monoclonal gammopathy of undetermined significance (MGUS)
 Waldenstrom macroglobulinemia
 Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes
(POEMS syndrome)
 Solitary plasmacytoma
 Castleman disease
 AL amyloidosis
 Heavy chain deposition disease
 Light chain deposition disease
 42

Questions:

1. Nucleoside is made of all except:

a. Pyrimidine
b. Sugar
c. Histone
d. Purine
2. Concentration of DNA is measured by:
a. Infrared examination
b. Deoxy ribose estimation
c. Absorption at 260 nm
d. Ultrasound examination
3. The two strands of DNA are held together by:
a. Van der waals bond
b. Hydrogen bond
c. Covalent bond
d. Ionic interaction
4. Chargaff rule states that :
a. A+G = T+C
b. A/G = C/T
c. A = U = T = G = C
d. A+T = G+C
5. At the physiological pH, the DNA molecules are:
a. Positively charged
b. Negatively charged
c. Neutral
d. Amphipathic
6. Which form of DNA is predominantly seen?
a. Z
b. A
c. C
d. B
7. What is the nature of bonds between the two nitrogenous bases on
opposite strands of double stranded DNA?
 43

a. 3’-5’ phosphodiester bond

b. 5’-3’ phosphodiester bond
c. Hydrogen bond
d. N-glycosidic bond
8. Intron is not found in which DNA?
a. Nuclear DNA
b. Mitochondrial DNA
c. B DNA
d. Z DNA
9. The protein rich in basic amino acids, which function in the packaging
of DNA in chromosomes, is:
a. Elastin
b. Collagen
c. Histones
d. Fibrinogen
10.Euchromatin is the region of DNA that is relatively :
a. Uncondensed
b. Condensed
c. Overcondensed
d. Partially condensed
11.Mitochondrial DNA is :
a. Horizontally inherited
b. Vertically inherited
c. Paternally inherited
d. Maternally inherited
12.Non coding RNA are all except:
a. siRNA
 44

b. miRNA
c. tRNA
d. mRNA
13.Normal role of miRNA is:
a. Regulation of gene expression
b. RNA splicing
c. Initiation of translation
d. DNA confirmational change
14.Introns are excised by:
a. DNAase
b. Helicase
c. snRNA
d. Restriction endonuclease
15.A mutation in the codon which causes a change in the coded amino acid
is known as:
a. Mitogenesis
b. Missense mutation
c. Somatic mutation
d. Recombination
16.HbS has defect in amino acid position:
a. 4 of alpha chain
b. 6 of beta chain
c. 11 of beta chain
d. 12 of alpha chain
17.Which of the following is not a feature of genetic code:
a. Degenerate
b. Ambiguous
c. Nonoverlapping
d. Not punctuated
18.Enzymes involved in formation of RISC complex include all except:
a. Drosha
b. Pasha
c. Dicer
d. Ribozyme
 45

19.A ten year old child with aggressive behaviour and poor concentration
is brought with presenting complaints of joint pain and reduced urinary
output. Mother gives history of self mutilative behaviour stating that he
tends to mutilate his fingers. Which of the following enzymes is likely to
be deficient in this child?
a. Adenosine deaminase
b. APRTase
c. Acid maltase
d. HGPRTase
20.End product of purine metabolism in non primate mammals is:
a. Uric acid
b. Ammonia
c. Urea
d. Allantoin
21.False regarding gout is:
a. Due to increased metabolism of pyrimidines
b. Due to increased metabolism of purines
c. Uric acid levels may not be elevated
d. Has a predilection for great toe
22.The gaps between segments of DNA on the lagging strand are sealed by:
a. DNA helicase
b. DNA topoisomerase
c. DNA phosphorylase
d. DNA ligase
23.Ends of chromosome replicated by:
a. Telomerase
b. Restriction endonuclease
c. Photolyase
d. Exonuclease
24.Which enzyme has proof reading function in PCR?
a. Taq polymerase
b. Pfu polymerase
c. T-7 polymerase
d. Bst polymerase
25.Telomerase are not active in:
 46

a. Germ cells
b. Hematopoeitic cells
c. Cancer cells
d. somatic cells
26.Okazaki fragments are produced during synthesis of:
a. ds DNA
b. ss DNA
c. m RNA
d. t RNA
27.For 1 peptide bond formation, how many high energy phosphates are
required:
a. 1
b. 2
c. 3
d. 4
28.All of the following are involved in micro RNA synthesis except:
a. Sasha
b. Pasha
c. Drosha
d. Dicer
29.Double reciprocal plot is
a. Lineweaver Burk plot
b. Edie Hofstee plot
c. Hanes plot
d. Michelis menten equation
30.If Km Increases but Vmax remains same, the type of enzyme inhibition is
a. Competitive
b. Non - competitive
c. Mixed
d. Uncompetitive
31.All are true about isoenzymes except
a. Different Km value
b. Act on different substrate
c. Have different electrophoretic mobility
d. Have different physical properties
 47

32.Oxidation reduction reaction occurs with all of the following enzymes

except
a. Hydrolases
b. Peroxidases
c. Oxidases
d. Dehydrogenases
33.The lactate dehydrogenase (LDH) levels are increased in –
a. Myocardial infarction
b. Acute pancreatitis
c. Diabetes mellitus
d. Acute glomerulonephritis
34.A patient admitted to ICU with AMI suffers a second attack on the
fourth day. Which of the following should be used to confirm the
diagnosis?
a. Troponin-T
b. Troponin-I
c. CPK-MB
d. LDH
35.Transfer of an amino group from an amino acid to an alpha keto acid is
done by?
a. Transaminases
b. Aminases
c. Transketolase
d. Decarboxylase
36.The amino acid which serves as a carrier of ammonia from skeletal
muscle to liver is:
a. Glutamine
b. Alanine
c. Methionine
d. Arginine
37.Which product of citric acid cycle is used in detoxification of ammonia
in brain?
a. Oxaloacetate
b. Alpha ketoglutarate
c. Succinate
 48

d. citrate
38.Urea cycle occurs in
a. GIT
b. Spleen
c. Kidney
d. liver
39.Sources of nitrogen in urea cycle are:
a. Glutamate and ammonia
b. Arginine and ammonia
c. Aspartate and ammonia
d. Uric acid
40.Urea cycle enzyme is:
a. Glutaminase
b. Asparaginase
c. Glutamate dehydrogenase
d. Arginosuccinate synthetase
41.At physiological pH, carboxy terminal of a peptide is:
a. Positively charged
b. Negatively charged
c. Neutral
d. Infinitely charged
42.Which one of the following can be a homologous substitution for
isoleucine in a protein sequence?
a. Methionine
b. Aspartic acid
c. Valine
d. arginine
43.The amino acid having imino side chain is:
a. Lysine
b. Histidine
c. Tyrosine
d. proline
44.Basic amino acids are all except:
a. Arginine
b. Proline
 49

c. Lysine
d. Histidine
45.Non essential amino acid is:
a. Tyrosine
b. Phenylalanine
c. Lysine
d. Threonine
46.Amino acid with dissociation constant closest to physiological pH is:
a. Serine
b. Histidine
c. Threonine
d. Proline
47.Amino acid secreted in cystinuria are all except:
a. Ornithine
b. Arginine
c. Histidine
d. Lysine
48.Which of the following is not synthesized from tyrosine:
a. Norepinephrine
b. Melatonin
c. Thyroxine
d. Dopamine
49.Which amino acid does not show post-translational modification?
a. Selenocysteine
b. Triidothyronine
c. Hydroxyproline
d. Hydroxylysine
50.In phenylketonuria the main aim for first line therapy is
a. To replace the deficient product
b. To reduce the substrate for the enzyme
c. Change in confirmation of the enzyme
d. Supplementation of the limiting AA
51.The mode of action of phenylbutyrate in urea cycle defects is by :
a. Decreasing nitrogen absorption
b. Providing extra ATP
 50

c. Removing Nitrogen by alternate route

d. Increasing gut motility
52.Ramachandran plot is used to predict:
a. Viral load in HIV infection
b. Histopathological derangement in oral cancer
c. Secondary structures of proteins
d. Configuration of carbohydrates
53.Heme synthesis requires all except:
a. Iron
b. Glycine
c. Alanine
d. Succinyl CoA
54.Pigment providing colour to stool is:
a. Stercobilinogen
b. Urobilinogen
c. Mevobilirubin
d. Bilirubin
55.Porphobilinogen is formed from how many molecules of ALA?
a. 1
b. 2
c. 3
d. 4
56.Zinc containing enzyme are all except:
a. Carbonic anhydrase
b. Alcohol dehydrogenase
c. ALA dehydratase
d. ALA synthase
57.In hemolytic anemia, which of the following is not raised:
a. Serum bilirubin
b. Urinary bilirubin
c. Urinary urobilinogen
d. Fecal stercobilinogen
58.All of the following is raised in hepatic jaundice except:
a. ALT
b. AST
 51

c. ALP
d. Serum bilirubin
59.Conjugation of bilirubin in liver is done by addition of:
a. Acetate
b. Sulphate
c. Methyl group
d. Glucuronic acid
60.Most of the bilirubin in bile is:
a. Alpha bilirubin
b. Beta bilirubin
c. Gamma bilirubin
d. Delta bilirubin
61.In obstructive jaundice, colour of stool is:
a. Green
b. Black
c. Mustard coloured (deep yellow)
d. Clay coloured (pale)
62.In hemoglobin, iron is bound to:
a. Histidine
b. Arginine
c. Proline
d. Aspartic acid
63.Glycolytic enzyme inhibited by fluoride:
a. Glucokinase
b. Hexokinase
c. Enolase
d. Aldolase
64.3 ATP in anaerobic glycolysis occurs with which fuel?:
a. Glucose
b. Glycogen
c. Fructose
d. Galactose
65.Anticoagulant used to estimate glucose from a sample sent from PHC is:
a. NaF
b. EDTA
c. Sodium citrate + EDTA
 52

d. Potassium oxalate + NaF

66.After overnight fasting, levels of glucose transporters are reduced in:
a. Brain cells
b. Hepatocytes
c. Adipocytes
d. RBCs
67.Pyruvate can be converted directly to all of the following except:
a. PEP
b. Alanine
c. Acetyl CoA
d. Lactate
68.Arsenite inhibits all except:
a. PDH
b. Lipoic acid
c. Branched chain keto acid dehydrogenase
d. Isocitrate dehydrogenase
69.Congenital lactic acidosis may occur d/t defect in:
a. Pyruvate decarboxylase
b. PDH
c. Transketolase
d. Succinate dehydrogenase
70.In vivo control of citric acid cycle is effected by:
a. Acetyl CoA
b. Coenzyme A
c. ATP
d. Citrate
71.About oxidative phosphorylation, true is:
a. Generation of ATP
b. Generation of ADP
c. Utilization of ATP
d. Utilization of NADH
72.Cytosolic cytochrome c mediates:
a. Electron transport
b. Glycolysis
c. necrosis
 53

d. apoptosis
73.Reducing substance in urine is seen in all except:
a. Lactose intolerance
b. PKU
c. Galactosemia
d. Fanconi’s anemia
74.Which of the following pairs of sugars are both non-reducing?
a. Sucrose & lactose
b. Sucrose & maltose
c. Sucrose and trehalose
d. Sucrose & isomaltose
75.UDP glucose is used for all except:
a. Glycogen synthesis
b. Galactose metabolism
c. Heparin synthesis
d. Sphingolipid synthesis
76.Glucosamines used in the treatment of:
a. Arthritis
b. Niemann Pick Disease
c. Alzheimer’s Disease
d. Cancer
77.Following are the tests done for proteins, sugars and ketones. Which
will be positive in starvation state in urine?

(i) (ii) (iii)

a. (i) & (ii)
b. Only (ii)
c. Only (iii)
d. (ii) & (iii)
78.Most important rate limiting enzyme of glycolysis is:
 54

a. PFK-1
b. Pyruvate kinase
c. Glucose 1,6- bisphosphatase
d. Hexokinase
79.Which vitamin is required for glycogen phosphorylase?
a. Vit. B1
b. Vit. B2
c. Vit. B3
d. Vit. B6
80.Rapid source of energy for exercising muscles after 1st minute is
a. Blood glucose
b. Glycogenolysis
c. Stored ATP
d. Stored Phosphocreatine
81.Identify the correct regulatory molecules:

a. A= Glucagon; B= Insulin
b. A= Epinephrine; B= Glucagon
c. A=Epinephrine ; B= Insulin
d. A= Insulin; B= Glucagon
82.True about RAGE is
a. It is a receptor
b. Interacts with glycated end products
c. Plays important role in diabetic complications
d. All of the above
83.A 10 year old boy presents to emergency with a fainting episode during
playing football. Blood examination reveals hypoglycemia, raised levels
of ketone bodies, lactic acid & trigylcerides. On examination, liver &
 55

kidneys were enlarged. Histopathology of liver shows excess deposits of

normally formed glycogen. What is the diagnosis?
a. Von Gierke’s disease
b. Pompe’s disease
c. Cori’s disease
d. McArdle’s disease
84.Exclusively breast-fed neonate presents to emergency in the 7th month
of life with complaints of vomiting, lethargy and poor feeding. The
resident on duty suspects inborn error of metabolism. Urine
examination was negative by glucose-oxidase test, but positive in
Benedict's test for reducing substance. Most likely IEM is:
a. Neonatal Diabetes Mellitus
b. Essential Fructosuria
c. Galactosemia
d. Hereditary Fructose Intolerance
85.Omega 6 fatty acids are all except?
a. Linoleic acid
b. α-Linolenic acid
c. γ- Linolenic acid
d. Arachidonic acid
86.Chitotriosidase, TRAP and ACE enzymes are elevated. The following
histopathological picture is seen on bone marrow examination. What is
the likely diagnosis?

a. Fabry’s Disease
b. Gaucher’s Disease
c. Niemann Pick Disease
d. Sandhoff’s Disease
87.Dried blood drop of an infant can be used to know:
a. Blood sugar
 56

b. Inborn errors of metabolism

c. Hepatitis
d. Cataract
88. A 56 year old homeless man presents to ER with increased fatigability
and exertional dyspnea. Physical examination shows significant lower
extremity edema and decreased sensation over the ankles and feet.
Further evaluation reveals cardiac dilation and increased cardiac
output. Which vitamin deficiency is most likely responsible for this
patient’s symptoms?
a. Riboflavin
b. Pyridoxine
c. Niacin
d. Thiamine
89.Vit B2 activity is measured by:
a. Glutathione-S-Transferase
b. Glutathione Reductase
c. Catalase
d. Tyrptophan pyrrolase