TOPIC ESSENTIAL TO KNOW NICE TO KNOW

NOT TO BE TESTED IN

EXAMINATION

1.

CELL Basics of cell structure, including overview of basic structure of cellular organelles and their functionsBasic concepts of separation of sub-cellular organelles (no details required)

2 ENZYMES

Nomenclatureandclassification

Systematic name, recommended name, IUPAC classification of enzymes, main classes of enzymes only (names, definition, general reaction catalyzed and one specific example of each class)

Sub-classes of enzymes

Properties of enzymes

Active site, lock and key and induced fit models of enzyme-substrate binding, specificity of enzymes- (reaction and substrate specificity – definition and anexample for each

Mechanism of action of an enzyme with regard to concept of activation energy of a reaction

Cofactors - metals and coenzymes (definition, constituents, classification, examples of coenzymes) and names of enzymes that require them

Concept of amino acids necessary in the active site of an enzyme

More examples of enzyme specificity

Amino acids present in active sites of enzymes

Factors that influenceenzyme activity

pH,temperature, substrate concentration, (concept of Km, Michaelis -Menten equation only),concentration of enzyme concentration of products

Lineweaver Burk curve

Inhibition of enzymes

Types of enzyme inhibition (competitive, non competitive, suicide inhibition), basic conceptswith an example for each type of inhibition, effects of inhibitors on Km and Vmax of an enzyme-catalysed reaction, examples of commonly used drugs that act by competitive inhibition of enzymes, examples of non-competitive enzyme inhibition (eg, organophosphorus / cyanidepoisoning).

Effects of inhibitors on the Lineweaver-Burk curve

Effects of inhibitors on the Lineweaver Burk curve

Isoenzymes Definition, examples (lactate dehydrogenase and creatine kinase), concept of separation of isoenzymes by electrophoresis

Details of separation and quantitation of isoenzymes

Diagnostic and therapeuticenzymes (Clinically usefulEnzymes)

AST, ALT, ALP, LDH, CK and amylase (normal values and conditions in which levels are abnormal). Examples of enzymes used in treatment and their indications

5-nucleotidase,gamma-glutamyltransferase(normal values and conditions in which levels are abnormal)

Regulation of enzyme activity

Overview of mechanisms involved in regulating the activity of enzymes (induction, repression,covalent modification - phosphorylation and dephosphorylation- and allosteric regulation, with 2 examples for each)

3 CHEMISTRY AND METABOLISM OF CARBOHYDRATES

Chemistry of carbohydrates

Functions, basic overview of classification of carbohydrates with physiologically important examples, basis of Benedict’s test for reducing sugars, concept of deoxy and amino sugars,components of physiologically important disaccharides and polysaccharides, concept of homo- and heteropolysaccharides with physiologically important examples and their importance in the body.

Structures of carbohydrates,isomerism of sugars, mutarotation, chemical reactions of sugars,mucopolysaccharidosis

Metabolism of carbohydrates

Digestion of carbohydrates

Examples of common dietary carbohydrates and the foods that they are present in, enzymes involved in digestion of carbohydrates, sources, sites and actions of the enzymes that digest carbohydrates,end products of digestion and their absorption, rationale for the composition and use of oral rehydration solutions (ORS), lactose intolerance.

Glycolysis Definition, importance, cellular site, pathway, importance of aerobic and anaerobic forms of glycolysis, energetic, overview of regulation of glycolysis, Rapaport- Leubering shunt and its physiological importance, concept of lactic acidosis and common causes and

Pathway of glycolysis

Role of fructose 2,6 bisphosphate in regulation of glycolysis

conditions in which seen, importance of inhibition of enolase by fluoride in blood samples collected for glucose estimation, concept of substrate level phosphorylation

Citric acid cycle

Pyruvate dehydrogenase as a link between glycolysis and Krebs’ cycle (no details of reaction mechanism required), definition, importance, cellular site, pathway (including intermediates and enzymes involved, excluding details of reactions involved), concept of anaplerosis,amphibolic nature of TCA cycle, energetics

Pathway of citric acid cycle

Regulation of pathway

HMP shunt Definition, importance, organ sites, cellular site, overview of pathway showing starting material and products, importance of end-products formed - ribose for nucleic acid synthesis and NADPH for synthesis of various lipids, maintenance of reduced form of iron in haemoglobin, reduced glutathione and its importance in maintaining red cell membrane integrity, medically relevant enzymes in the pathway (glucose-6-phosphate dehydrogenase (G6PDH) and transketolase),clinical relevance of the deficiency of G6PDH.

Pathway of HMP shunt

Metabolism of glycogen

Glycogenesis

Glycogenolysis

Physiological importance of glycogen storage in the body (including sites and importance of each site), overview of pathway of synthesis (starting material, action of glycogen synthase and branching enzyme and product), role of hormones on the process (action of glycogen synthase) (details of regulation not required)

Physiological importance of glycogen breakdown in the body, overview of pathway of breakdown in the liver and muscle (starting material, action of phosphorylase and debranching enzyme and products obtained), role of hormones on the process (action of phosphorylase) (details of regulation not required), importance of reciprocal regulation of glycogenesis and glycogenolysis, examples of glycogen storage diseases (Von Gierke’s disease and McArdle’s disease)

Pathway of synthesis and breakdown of glycogen

Gluconeogenesis

Definition, substrates used,physiological importance, sites, overview of pathway with key intermediates and enzymes, Cori cycle, glucose-alanine cycle, role of hormones in regulation, concept of reciprocal regulation of glycolysis and gluconeogenesis (no details required)

Pathway of gluconeogenesis

Role of fructose 2,6 bisphosphate in regulation of gluconeogenesis

Uronic acid pathway

Overview of pathway showing starting material (glucose) and product (glucuronic acid), importance in conjugation of bilirubin and drugs.

Pathway of uronic acid formation, essential pentosuria

Metabolism of galactose

Dietary sources of galactose,overview of pathway by which galactose is metabolized (showing the sites of 3 main enzymes involved), eventual fate of galactose in the body,galactosemia (definition, causes, clinical manifestations and rationale of therapy)

Pathway of galactose metabolism

Metabolism of fructose

Dietary sources of fructose, overview of pathway by which fructose is metabolized (showing entry into glycolysis and into formation of triacylglycerol), importance of fructose in seminal fluid

Pathway of fructose metabolism and associated disorders

Minorpathways of carbohydratemetabolism

Polyol pathway and its importance in pathogenesis of complications of diabetes mellitus

Regulation of blood glucose levels

Role of dietary carbohydrates, role of hormones (insulin, glucagon, glucocorticoids, catecholamines), role of liver and kidney.

Diabetesmellitus

Types and pathogenesis, concept of insulin resistance,metabolic derangements, clinical features, relevant investigations, diagnostic criteria (WHO criteria), concept of impaired fasting glucose and

impaired glucose tolerance, basic principles of treatment.

Laboratoryinvestigations in diabetes mellitus

Blood glucose estimations (fasting and post-prandial), glycated haemoglobin, urinalysis for glucose, ketone bodies, proteins microalbuminuria, role of glucose tolerance test in diagnosis of diabetes mellitus, indications for and interpretation of results of a glucose tolerance test (OGTT), serum lipid profile in diabetics

Hypoglycemia Definition, importance, causes, clinical manifestations, treatment.

3 CHEMISTRY AND METABOLISM OF LIPIDS

Chemistry of lipids

Generalfeatures

Classification of lipids

Definition of a lipid,properties with regard to solubility and hydrophobicity,important functions of lipids in the human body, importance of lipids in causation of disease (atherosclerosis with subsequent myocardial infarction and stroke, obesity, cholecystitis)

Major types of lipids in the body (classification into simple, complex and precursor or derived lipids),medically relevant examples

Structures of various types of lipids

Fatty acids

Simple lipids (fats)

Steroids

of each type and the importance of each type in the body

Composition of a fatty acid, system of nomenclature (including systematic names and symbols), with C and n numbering of fatty acids, classification system based on chain length, degree of saturation (saturated and mono- and polyunsaturated fatty acids), and nutritional requirement, concept of saturated fatty acids in animal fat and unsaturated fatty acids in plant fats, names of essential fatty acids and their functions, importance of 3 and 6fatty acids (dietary sources and their health benefits), concept of importance of saturated and unsaturated fats in one’s diet (including hydrogenation of oils).

Basic concept of cis and trans forms of fatty acids and the health hazards of trans fats, basic concept of structure of a fat with its components of glycerol and fatty acids, basic concept of mono, di- and triacylglycerols and where they are found in the body.

Ability to recognize the structure of the steroid nucleus and that of cholesterol, functions of cholesterol, health hazards associated with high blood levels of cholesterol, basic concepts of involvement of

Structures of fatty acids

Complex lipids

Miscellaneous

lipids in the pathogenesis of atherosclerosis, cholelithiasis and obesity

Phospholipids (definition, components, amphipathic nature, functions, examples and importance of each type - viz. phosphatidylcholine [including importance of surfactant in health and disease, phosphatidylinositol and sphingomyelin), glycolipids (definition, components, functions, examples [basic concept of cerebrosides and gangliosides] and importance of each type in the body

Basic concept of involvement of lipids in demyelinating diseases and sphingolipidosis,lipoproteins (definition, basic structure, types, components of each type, function of each type, importance in health and disease), micelles (definition, structure and importance), liposomes (definition, structure and importance), biological membranes (structure and importance)

Metabolism of lipids

Digestion of lipids

Names of main lipids present in the diet, enzymes responsible for digestion of lipids and their sources and sites of action, actions of the various enzymes, role of bile in lipid digestion and absorption,

names of end-products of lipid digestion, process of absorption of lipids, steatorrhoea, salient features of formation and metabolism and physiological importance of chylomicrons

Fatty acid oxidation

Biosynthesis of fatty acids

Metabolism in the adipose tissue

Importance of oxidation of fatty acids in the body, types of oxidation fatty acids can undergo, beta-oxidation of fatty acids (site, activation of a fatty acid, the role of carnitine, outline of steps involved and energetic)

Conditions under which it occurs and sites involved, starting material and end products, source of acetyl CoA, role of acetyl CoA carboxylase, overall role of fatty acid synthase (individual enzymes and reactions not required), Importance of NADPH in the pathway and its sources, role of the nutritional state and insulin as factors that regulate synthesis of fatty acids

Concept of esterifcation of fatty acids to form TAG stored in adipose tissue, metabolism in the adipose tissue with regard to lipogenesis and lipolysis

End-products of beta-oxidation of odd chain fatty acids.

Alpha-oxidationof fatty acids and its importance

Conditionswhere fatty acid oxidation is impaired

Elongation and desaturation of fatty acids

Pathway of beta oxidation

End-products of beta-oxidation of odd chain fatty acids.

Alpha-oxidation of fatty acids and its importance

Conditions where fatty acid oxidation is impaired Pathway of biosynthesis of fatty acids

Elongation and desaturation of fatty acids

(conditions where it occurs, enzymes involved and products obtained) and its regulation by hormones

Metabolism of ketone bodies

Names of the ketone bodies, their importance, pathway of ketogenesis and utilization of ketone bodies and sites where these occur, factors that favour ketone body formation, abnormalities associated with metabolism of ketone bodies and their clinical relevance, conditions that lead to ketoacidosis

Metabolism of cholesterol

Functions of cholesterol, sources of cholesterol in the body (dietary and endogenous), cellular site of biosynthesis of cholesterol,basic overview of biosynthesis of cholesterol (showing formation of HMG CoA and action of HMG CoA reductase and formation of cholesterol without showing any other intermediates), regulatory enzyme involved in biosynthesis of cholesterol, importance of maintaining normal cholesterol levels in blood and ways to reduce blood cholesterol levels (including mechanism of action of statins and other lipid lowering agents)

Bile acids (names, source and functions), overview of synthesis (regulatory enzyme), enterohepatic circulation of bile salts,pathogenesis of cholelithiasis

Pathway of biosynthesis of cholesterol

Pathway of biosynthesis of bile acids

Metabolism of lipoproteins

Brief overview of metabolism of VLDL, LDL and HDL (including normal values).

Pathogenesis of atherosclerosis, association of high levels of VLDL and LDL with atherosclerosis and anti-atherogenic effect of HDL.

Dyslipidemias – causes and consequences (secondary causes and familial hypercholesterolemia)

Risk factors for atherosclerosis and coronary artery disease, prevention ofcoronary artery disease.

Overview of metabolic syndrome

Lipoprotein (a)

Eicosanoids Names and functions of various eicosanoids, overview of pathway of synthesis (site of action of PLA2 and cyclooxygenase to be emphasized and site of action of NSAIDs; role of aspirin as an anti-platelet agent)

Therapeutic uses of prostaglandins

Pathway of biosynthesis of eicosanoids

Phospholipids Clinical relevance of lecithin-sphingomyelin (L/S) ratio in amniotic fluid

Basic structure of phospholipid

Sites of action of variousphospholipases

Examples of sphingolipidosis(Niemann-Pick’s, Tay-Sach’s and Gaucher’s

Structure and synthesis of phospholipids

Sphingolipidosisother than the examples specified.

disease)

Miscellaneous Role of liver in lipid metabolism, fatty liver (causes, including role of lipotropic factors, and consequences)

Overview of metabolism of alcohol

4 CHEMISTRY AND METABOLISM OF PROTEINS

Amino acids General structure,classification based on side chains, nutritionally essential and non essential amino acids, properties of amino acids (viz. peptide bond formation, zwitter ion formation, reaction with ninhydrin)

Structures of amino acids

Peptides and proteins

Names of some physiologically important peptides, structure of proteins (at primary, secondary, tertiary and quaternary levels),schematic representation of primary and secondary structures, classification of proteins based on axial ratio (fibrous and globular),physiologically rekevant properties of proteins, denaturation.

Overview of structure and importance of haemoglobin, myoglobin and collagen

Outline of the elucidation of primary structure of a protein, precipitation reactions of proteinfunction of chap-erone proteins

Methods of elucidation of structure of protein

Digestion and absorption

Enzymes involved in the digestion of proteins, sites of action, end-products formed, overview of amino acid absorption

Meister cycle

Disorders of protein digestion and absorption.

Generalpathways of amino acid catabolism

Transamination and deamination, enzymes and coenzymes involved, products formed and importance of each of these reactions

Details of mechanisms of the reactions

Ammoniametabolism

Sources of ammonia, role of glutamine and urea formation, urea cycle with enzymes involved, disorders associated with ammonia metabolism, pathogenesis of hepatic coma and biochemical basis of its treatment, disorders of the urea cycle, normal blood urea level, blood urea nitrogen (BUN) levels, azotemia and its clinical significance

Structures of intermediates of urea cycle

Regulation of urea cycle

Metabolism of individualamino acids

Functions and physiologically important reactions in which glycine, methionine, phenylalanine, tyrosine, tryptophan and histidine are involved.

Specialized products derived from amino acids

Disorders associated with amino acid metabolism (hyperphenylalaninemia and phenylketonuria, alkaptonuria).

Importance of neonatal screening for inborn errors of amino acid metabolism.

Concept of maple syrup urine disease in abnormality in metabolism of branched chain amino acids

Metabolic pathways of synthesis and catabolism of any amino acids

Maple syrup urine disease

Plasmaproteins

Classification, examples and functions of plasma proteins, separation by electrophoresis, normal values of total proteins and albumin.

Details of process of electrophoresis

Common clinical conditions in which plasma protein levels are abnormal and the reasons why these changes occur.

Importance of the albumin: globulin ratio (A: G ratio), normal value and common clinical conditions in which the ratio is abnormal.

5 VITAMINS

Generalproperties of vitamins

Definition, classification, comparison of clinically relevant features of fat and water soluble vitamins.

Concepts of hypo and hypervitaminosis and recommended daily allowances.

Fat-soluble vitamins

Vitamin A Dietary sources. Precursor form. Absorption from diet. Various forms of vitamin A. Biochemical functions Role in Wald’s visual cycle, Daily dietary requirement. Deficiency – causes, manifestations and treatment

Hypervitamino-sis A

Structure and chemical properties of vitamin A

Vitamin D Dietary sources of vitamin D3.Synthesis in the body. Conversion to calcitriol. Biochemical functions Role in bone mineralization and calcium homeostasis. Daily requirement, deficiency (rickets and osteomalacia) – causes, manifestations, Biochemical findings in blood and principles of treatment.

Structure and chemical properties of vitamin D

Vitamin E Dietary sources Role as an antioxidant. Relationship to action of glutathione peroxidase. Deficiency leading to fragility of RBCs

Structure and chemical properties of vitamin E

Vitamin K Sources,Intestinal synthesis, Absorption from GIT, Forms (K1, K2 and K3), Biochemical role, Vitamin K cycle. Basis of action of dicumarol, Requirement. Deficiency – causes, manifestations (including hemorrhagic disease of the new born), and principles of treatment

Structure and chemical properties of vitamin K

Water soluble vitamins

Thiamine Dietary sources. Functions (coenzyme form, physiologically most important reactions in which it is required). Requirement. Deficiency – causes, manifestations (including Wernickes Korsakoff syndrome - causes, clinical features and principles of treatment).

Assessment of thiamine status by assaying the activity of RBC transketolase

Riboflavin Dietary sources. Functions (coenzyme forms, physiologically most important reactions in which they are required). Requirement. Deficiency – causes and manifestations

Niacin Sources (including from tryptophan).Functions (coenzyme forms, physiologically most

important reactions in which they are required). Requirement. Deficiency – causes and manifestations

Pyridoxine Dietary sources. Functions (coenzyme forms, physiologically most important reactions in which they are required) Requirement. Deficiency – causes and manifestations. Rationale for supplementation in treatment of tuberculosis

Mechanism of transamination reactions

Biotin Sources.Role in carboxylation reactions. Examples of most important enzymes that require biotin

Folic acid Dietary sources. Functions (coenzyme forms, physiologically most important reactions in which they are required Role of folic acid in 1C metabolism - 1C donor reactions (serine hydroxymethyl transferase) and 1C acceptor reactions (methionine synthase, thymidylate synthase, and purine synthesis) Relationship with Vit. B12. Folate trap. Requirement. Deficiency – causes and manifestations. Importance of supplementation in periconceptual period.Folate antagonists (actions of methotrexate, aminopterin,

sulphonamides)

Vitamin B12 Dietary sources. Absorption and role of intrinsic factor. functions (coenzyme forms, reactions for which they are required).Role in RBC maturation. Requirement Deficiency – causes and manifestations (megaloblastic and pernicious anemia, anemia) Importance of combined B12and folic acid administration in treatment of megloblastic anemia

Vitamin C Dietary sources. Functions (in collagen synthesis, iron absorption and as an antioxidant). Requirement. Deficiency – causes and manifestations

Role of vitamin C in the conversion of tyrosine to catecholamines, cholesterol to bile acids and catabolism of tyrosine

Vitamin-likesubstances

Lipoic acid Role in reactions involving pyruvate and alpha ketoglutarate in the citric acid cycle

Mechanism of the role of lipoic acid in these reactions

7 NUCLEOTIDE CHEMISTRY AND METABOLISM

Nucleotidechemistry

Purine and pyrimidine bases found in DNA and RNA Definition and examples of nucleosides and nucleotides. Functions of physiologically important nucleotides Examples of synthetic analogues of purine/pyrimidine bases and nucleosides used as

Structures of purine and pyrimidine bases.

therapeutic agents (anti-cancer drugs, anti-viral drugs and allopurinol)

Nucleotidemetabolism

Overview of the pathway of de novo synthesis of purine nucleotides, with names of only important intermediates, regulatory enzyme involved, salvage pathway for purine bases and nucleosides. Lesch- Nyhan syndrome (cause, biochemical basis of clinical features), overview of the pathway of degradation of purines to form uric acid. Hyperuricemia and gout (causes, clinical features, principles of treatment, including mechanism of action of allopurinol and probenecid).

Overview of pathway of pyrimidine nucleotide synthesis, regulatory enzyme, synthesis of thymidylate from dUMP (thymidylate syntase), salvage pathway for pyrimidines bases and nucleosides.

Mechanism of action of methotrexate and 5-flurouracil (anti-cancer drugs)

Pathways of de novo synthesis of purines and pyrimidines

Pathways of degradation of purines and pyrimidines.

8 BIOENERGETICS

Role of ATP Role of ATP as the “energy currency” of the cell. Role of high energy phosphates in energy capture and transfer e.g., role of

Concept of free energy, enthalpy, entropy, endergonic and exergonic reactions.

creatine in muscle. First and second laws of thermodynamics

Details of free energy, enthalpy, entropy

The respiratory chain and oxidativephosphorylation

Sources of reducing equivalents in the cell (NADH and FADH2).Role of mitochondria as the “power house” of the cell Substrate level and oxidative phosphorylationSchematic representation of the electron transport chain Role of the respiratory chain as an electron transporter and a proton pump Overview of chemiosmotic theory of oxidative phosphorylationExamples of inhibitors of electron transport chain and uncouplers of oxidative phosphorylation(physiological and pharmacological) Role of brown fat (non-shivering thermogenesis and role of uncoupling protein/ thermogenin). Transport of cytosolic NADH into the mitochondria (mitochondrial shuttle systems)

Concept of redox potentials and proton motive force (pmf)

Role of ADP in regulatin g ATP synthesis(respiratorycontrol)

Transporterspresent on the innermitochondrial membrane

Structure of complex V

Details of mechanism of electron transfer in each electron transport complex

Q cycle

“Binding change” mechanism of ATP synthesis in complex V

9 HOMEOSTATIC MECHANISMS IN THE BODY

Acid base balance

Definition of acid, base and buffer Normal pH of body fluid and importance of maintaining normal pH Sources of hydrogen ions in the body. Buffers of body fluids Henderson – Hassalbalch

equationMaintenance of acid – base balance

Role of buffers (with emphasis on the bicarbonate buffer system)

Role of the lungs Role of the kidneys

Simple acid-base disorders: Major causes and clinical features of: Metabolic acidosis

(including importance of anion gap) and alkalosis

Respiratory acidosis and alkalosis

Assessment and interpretation of arterial blood gas (ABG)Rules of compensation in metabolic/respiratory acidosis/alkalosis

Fluid and electrolyte balance

Distribution of water in various body compartments. Intra- and extracellular fluid composition (sodium and potassium) Blood volume and osmalality Regulation of osmolality

– role of anti-diuretic hormone (ADH)

Major causes and clinical features of dehydration

Composition of commonly used intravenous fluids and their indications.

Sodium: normal levels in the

blood physiological functions regulation (renin-

angiotensin-aldosterone

system) major causes, clinical

features and basic principles of treatment of:

hyponatremia hypernatremia

Potassium: normal levels in the

blood physiological

functions regulation major causes, clinical

features and basic principles of treatment of:

hypokalemia hyperkalemia

Chloride : normal levels in the

blood physiological functions regulation

Immunology: Concepts of innate and adaptive immunity Types of immune responses – Humoral and cell-mediated Types and functions of immunoglobulinsStructure of IgG (diagrammatic representation)Multiple myeloma – biochemical abnormalities and laboratory diagnosis. Immunoassays – principles Basic concepts of congenital and acquired immunodeficiency syndrome (AIDS)

Cell-mediated immunity

Majorhistocompatibility complex

Complement system

Cell-mediated immunity

Majorhistocompatibility complex

Complement system

MINERALS Concept of macro and micro minerals and examples.

Calcium:Sources and daily requirement FunctionsAbsorption (and regulation of absorption)Regulation (only role of PTH and Vitamin D)Major causes, clinical features, laboratory diagnosis and principles of treatment of hypocalcemia and hypercalcemia

Iron:Sources and daily requirement FunctionsAbsorption (and regulation of absorption).Overview of role of divalent metal transporter-1 (DMT-1), duodenal cytochrome b (dcytb), haephestin, ferroportin and hepcidin.Storage and transport (role of ferritin and transferrin) Major causes, clinical features, laboratory diagnosis and principles of treatment of iron deficiency and overload states

Copper:Sources and daily requirement FunctionsRole of ceruloplasmin Wilson’s and Menke’s disease

Zinc: Sources and daily

requirement Functions (inc. role of metallothionein) Causes and clinical features of zinc deficiency

Magnesium:Sources and daily requirement Functions

Iodine:Sources and daily requirement FunctionsCauses and clinical features of iodine deficiency.

Flourine:Sources and daily requirement FunctionsCauses and clinical features of fluorosis

Functions of selenium, molybdenum

HAEM METABOLISM

Importance of haem (heme-containing proteins – hemoglobin, myoglobin, cytochromes) Basic features of structure. Heme synthesis

Overview of heme synthesis and its regulationPorphyria: major types (acute intermittent porphyria (AIP) and congenitalerythropoietic porphyria (CEP)) – causes, basis of clinical features in each type. Acquired porphyria: lead poisoning.

Heme degradation: Pathway of formation of bilirubin

Pathway of synthesis of haemTypes and causes of other porphyrias

Pathway of synthesis of haem Types and causes of other porphyrias

Conjugation and excretion of bilirubin (incl. congenital disorders)Hyperbilirubinemia – causes and differential diagnosisImportant physiological and pathological causes of jaundice in the newborn

FUNCTION TESTS:

Renal function test:

Functions of the kidney Estimation of non-protein nitrogenous substances in blood (urea and creatinine) Estimation of creatinine clearance and its importance Tests to assess tubular function – measurement of plasma and urine osmolality, basic principles of water deprivation test (ADH test) and urinary acidification test. Urinalysis:

Physicalcharacteristics and composition of normal urine. Major causes for presence of protein, reducing sugar, blood, ketone bodies, bile salts and bile pigments in urine Principles of important tests to detect the above mentioned substances in the urine(Sulphosalicylic acid

Liver function tests:

Thyroidfunction test:

test for proteins, Benedict’s test for reducing sugar, Benzidine test for blood, Rothera’s test for ketone bodies, Hay’s test for bile salts and Fouchet’s test for bile pigmens).

Functions of the liver. List the tests done to assess liver function in clinical practice Importance of estimation of common tests done to assess liver function:

1. Detoxification: Conjugated and unconjugated bilirubin (van den Bergh’s test) 2. Synthetic functions: Total protein and serum albumin levels, Prothrombin time 3. Markers of liver injury: alanine transaminase (ALT), aspartate transaminase (AST),Markers of cholestasis: alkaline phosphatase (ALP).

Differential diagnosis of the causes of jaundice using liver function tests.

Regulation of secretion of thyroid hormones Thyroid function tests (TSH and thyroxine levels).Importance of estimation of TSH in assessment of thyroid function tests.Measurement of total and

Adrenalfunction tests:

free thyroxine levels. Basic principles behind the laboratory diagnosis of hypothyroidism and hyperthyroidism

Functions of the adrenal cortex and medulla. Regulation of secretion of adrenocortical hormones. Basic test done for the laboratory diagnosis of adrenal hypofunction and hyperfunction (including principles for suppression and stimulation tests)

MOLECULAR BIOLOGY

The cell cycle, DNA and RNA structure,replication and repair:

Overview of the cell cycle (including overview of mitosis and meiosis) Modes of inheritance: autosomal (dominant and recessive), X-linked inheritance.Watson and Crick model of DNA structure Structure and functions of different types of RNA. Differences between nuclear and mitochondrial DNA. Structure of nucleosomes and function of histone proteins.Overview of organization of DNA in a chromosome. Semi-conservative mechanism of DNA replication (basic concept only)Overview of DNA replication in prokaryotes and eukaryotes (including important differences between the two):

Role of DNA

Details of eukaryoticreplication

Details of structure and types of chromosomes

Details of DNA repairmechanisms and other disorders of DNA repair.

Details of eukaryotic replication

Details of structure and types of chromosomes

Details of DNA repair mechanisms and other disorders of DNA repair.

Transcription

polymerase (including proof reading function), helicase, primase, topoisomerase and DNA ligase Diagrammatic representation of the events at the replication fork Okazaki fragments and its importance in replication.

Overview of role of major DNA repair mechanisms – mismatch repair, base excision repair, nucleotide excision repair and double strand break repair. Diseases associated with abnormalities of DNA repair systems – xeroderma pigmentosum and hereditary non-polyposis colon cancer (HNPCC) Structure and function of telomeres and role of telomerase (including end-replication problem and role of telomerase in cancer cells and stem cells)

Structure of a gene - concepts of exons and introns (concepts of mono- and polycistronic mRNA)Overview of the process of transcription in prokaryotes and eukaryotes – initiation, elongation and termination (including important differences)Regulation of initiation of transcription – role of

Generearrangement in

Details of eukaryotic transcription.

Details of splicing reactions,spliceosomes and ribozymes (“snurps”)

Translation and genetic code:

Mutations and regulation of gene expression

transcription factors, promoter, enhancers/repressors and response elementsPost-transcriptionalprocessing – capping, tailing and splicing (no details)

The genetic code and itscharacteristics (universal, unambiguous, degenerate, continuous/commaless), basis of degeneracy of the genetic code (wobble hypothesis).

Basic structure of prokaryotic and eukaryotic ribosomes. Structure of tRNA (diagram of clover leaf model of tRNA structure) and its function in protein synthesis.Function of aminoacyl tRNA synthase. Overview of the process of translation – initiation, elongation and termination (including important differences between prokaryotic and eukaryotic translation). Inhibitors of prokaryotic translation – antibiotics Post-translationalmodifications – five examples and physiological importance. Overview of protein folding and role of chaperones.

Mutagens with examples of physical, chemical and biological mutagens.

immunoglobulinheavy chain

Intracellular protein trafficking

Details of the process of translation

Regulation of geneexpression

RecombinantDNAtechnology and techniques in molecular biology:

Mutations (definition, types of mutations [point mutation{ substitution - transition and transversion}], deletion, insertion, frame shift mutation, mis-sense mutation, non-sense mutation and silent mutation), chromosomal mutations (deletion, inversion and translocation).Relationship with specific diseases – sickle cell anemia and chronic myeloid leukemia.

Prokaryotes - operon concept in prokaryotes using lac operon as an example.

Eukaryotes - Regulation of initiation of eukaryotic transcription: role of general and gene specific transcription factors Small interference RNA (siRNA) and micro RNA (miRNA).

Concepts of recombinant DNA, genetic engineering, biotechnology, cloning Restriction endonucleases Vectors for cloning – plasmids and phages Genomic and cDNA libraries Human genome project. Applications of recombinant DNA technology in medicine:

Production of therapeutic proteins Gene therapy Diagnosis of genetic

Regulation of gene expression by: 1. Alternative

splicing 2. DNA methylation 3. Histone

acetylation / deacetylation

4. RNA editing 5. Alterations of

RNA stability

Other operon models e.g., Tryptophan operon

The lytic – lysogenic genetic switch in lambda phage.

diseases and genetic counselingForensic investigation DNA vaccines Transgenic animals as models of human diseases

Principles and applications of techniques in molecular biology:

Polymerase chain reaction (PCR) Southern, northern and western blotting Restriction fragment length polymorphism (RFLP)DNA fingerprinting DNA sequencing Microarrays Fluorescent in situ hybridization (FISH)

METABOLISM OF XENOBIOTICS

Xenobiotics (definition andexamples), biochemical importance of the two phases of xenobiotic metabolism. Cytochrome P450 enzyme system (functions, properties [especially induction by drugs], its role in conversion of procarcinogens to carcinogens.Conjugation reactions(biochemical role, examples of glucuronidation and sulfation, conjugation with glutathione, acetylation and methylation)

Poisoning and environmental hazards

Causes, mechanism of toxicity, clinical features and principles of treatment of poisoning by lead,

organophosphates, mercury, cyanide and arsenic.

Environmental hazards (insecticides and pesticides,air pollutants, industrial hazards: e.g., Bhopal gas tragedy)

Mechanisms of actions of hormones

Classification and nature of hormones in each category, mechanism of action of hormones.

Carcinogenesis Biomedical importance of cancers. General features of tumours. Characteristics of benign and malignant tumours. Properties of cancer cells, molecular events involved in carcinogenesis (non-lethal DNA damage involving oncogenes, tumour suppressor genes, DNA repair genes and genes involved in apoptosis and clonal origin). Role of radiation, chemicals and viruses in carcinogenesis.Examples of cancer produced by each type of agent. Conditions with defective DNA repair that predispose to development of cancer, mutagens.Involvement of oncogenes and tumour suppressor genes in development of cancers, including examples and mechanisms of activation of oncogenes.Examples, functions and consequences of mutations in tumour suppressor genes.

Ames test for mutagenicity of a chemical

Role of genes involved in apoptosis and DNA repair in carcinogenesisImportant biochemical characteristics of malignant cells. Telomeres and telomerase and their importance in cancer cells. Tumour markers -characteristics of an ideal marker, examples and uses. Examples of drugs used in chemotherapy of malignancies and the biochemical mechanism of action of these drugs.

Nutrition Importance. Components and importance of each. Concept of balanced diet, glycemic index of food. Importance of dietary fibre. Basal metabolic rate. Specific dynamic action. Biological value of proteins. Concept of limiting amino acids. Nitrogen balance. PEM states. Obesity (including calculation and interpretation of BMI). Nutritional requirements in diabetes mellitus, coronary artery disease, pregnancy, childhood,