Important Questions from KUHS MBBS Biochemistry Previous Years' Papers

Paper 1 Topics

Most Frequent and Important Questions:

• Enzymes

  • Enzyme inhibition: Define different types (competitive, non-competitive, suicide) with examples and their significance. This is a very common Long Essay (LE) or Short Essay (SE) topic.

  • Isoenzymes and their clinical/diagnostic significance: Especially focusing on their role as cardiac markers. This is a highly recurring theme for SE, SN, and GPA.

  • Definition, classification, factors affecting enzyme activity, and mechanisms of enzyme regulation: These concepts are central and often form part of LEs or SEs.

  • Km value and its significance.

• Carbohydrate Chemistry & Metabolism

  • Regulation of blood glucose levels: Including normal reference ranges, hormones involved, and homeostasis in fed and starvation states. This is a frequent LE or SE question, often presented as a case study.

  • HMP Shunt pathway: Its significance, products (e.g., NADPH), and importance in erythrocytes. This topic is consistently asked as an SE or SN.

  • Glycogen metabolism: Explain glycogenesis and glycogenolysis, including their regulation.

  • Glycogen storage diseases: Particularly Von Gierke's disease (enzyme defect, clinical features). These often appear as SN, GPA questions, or within case studies.

• Lipid Chemistry & Metabolism

  • Beta Oxidation: Define the process, describe its steps, regulation, and calculate the energetics (e.g., for palmitic acid). This is a very common LE question.

  • Ketone bodies: Names, synthesis (ketogenesis), utilization (ketolysis), and causes of ketosis/ketoacidosis. This topic frequently appears as an SE or SN.

  • Reverse cholesterol transport: A frequent Short Note.

• Protein Chemistry & Metabolism

  • Phenylalanine and Tyrosine metabolism: Catabolism, synthesis of biologically important compounds, and associated inborn errors (e.g., Phenylketonuria, Alkaptonuria, Albinism). This topic is frequently a Long Essay, often presented as a case study.

  • Urea cycle: Describe the reactions, regulation, and associated disorders of ammonia disposal/toxicity. This is a very common SE or LE.

  • Glycine metabolism: Synthesis and biologically important compounds formed from it.

• Minerals

  • Iron metabolism: Absorption, transport, storage, regulation of homeostasis, biochemical functions, and associated disorders (e.g., anemia). This is a highly significant topic, often appearing as an LE or SE, frequently with case studies.

  • Calcium metabolism: Plasma regulation, hormonal regulation, and biochemical functions. Also a very frequent LE or SE, sometimes with case studies.

• Vitamins

  • Vitamin D: Synthesis, sources, daily requirements, biochemical functions, and deficiency manifestations. Consistently asked as an LE or SE.

  • Vitamin A: Sources, biochemical functions, and deficiency manifestations. Frequent SE.

  • Thiamine: Sources, biochemical functions, and deficiency manifestations. Frequent SE.

  • Folate and Vitamin B12: Their biochemical role, deficiency manifestations (e.g., megaloblastic anemia), and concepts like "folate trap". These are important SE and SN topics.

• TCA Cycle & Biological Oxidation

  • Electron Transport Chain (ETC): Components, diagram, chemiosmotic hypothesis, and inhibitors. This is a very common LE or SE.

  • TCA Cycle: Reactions, amphibolic role, and energetics.

• Nutrition

  • Protein energy malnutrition: Causes, clinical features, biochemical manifestations, and treatment of Kwashiorkor and Marasmus. Frequently appears as SE or SN.

  • Dietary fibre: Definition, examples, and biomedical importance/hypocholesterolemic effect.

Other Important Questions:

• Cell & Sub-cellular Organelles: Mitochondria (structure and functions), Active transport, Peroxisomes, Biochemical basis of Zellweger’s syndrome, Golgi complex and its marker enzyme, Ribosomes, Endoplasmic Reticulum, Lysosomes, Components of membrane altering fluidity.

• Enzymes: Cardiac markers (specific names), Therapeutically important enzymes, Km value and its significance, IUMB classification, Diagnostic importance of enzymes.

• Carbohydrate Chemistry & Metabolism: Polysaccharides (classification, clinical applications), Fate of pyruvate, Glucose transporters, Galactosemia (enzyme defect), Digestion and absorption of carbohydrates, Glycolysis (energetics, regulation), Hypoglycemia, Cori's cycle and its significance, Renal glycosuria, Sucrose as non-reducing sugar, 2,3 BPG significance.

• Lipid Chemistry & Metabolism: Cholesterol metabolism (regulation of synthesis, functions), Essential fatty acids (names, deficiency features), Phospholipids (structure, classification, functions), Fatty liver, Lipotropic factors. Digestion and absorption of lipids.

• Protein Chemistry & Metabolism: Essential amino acids, Biologically important peptides, Protein digestion/absorption, Protein structure (primary, secondary, denaturation), Nitrogen balance, Homocystinuria, Alkaptonuria.

• Minerals: Copper and zinc (functions, containing enzymes, Wilson's disease), Functions of iodine, Selenium functions, Fluoride functions.

• Vitamins: Vitamin C (sources, daily requirement, deficiency), Vitamin K (biological role), Vitamin B6 (functions).

• TCA Cycle & Biological Oxidation: Substrate level phosphorylation, Amphibolic role of TCA cycle, Inhibitors of ETC.

• Nutrition: Dietary fibre importance.

• Integration of Metabolism: Role of Liver in integration of metabolism.

Paper 2 Topics

Most Frequent and Important Questions:

• Nucleotide Chemistry & Metabolism

  • Gout: Clinical features, biochemical basis, diagnosis, causes (primary gout), and biochemical basis of management (e.g., allopurinol). This is an extremely common topic, often appearing as an LE or SE, frequently in case study format.

  • Purine catabolism: Outline the pathway, regulation, and significance of the salvage pathway. Salvage pathway is consistently asked.

  • Lesch-Nyhan syndrome: Enzyme defect and clinical features. This is a very frequent GPA question.

• Acid-Base & Fluid-Electrolyte Balance

  • Acid-base homeostasis: Explain the mechanisms of maintaining blood pH, especially the role of kidneys (renal regulation) and buffer systems. This is a consistently high-yield topic, frequently appearing as an LE or SE, often within a complex clinical case study.

  • Metabolic acidosis/alkalosis and Respiratory acidosis/alkalosis: Definition, causes, biochemical findings, and compensatory mechanisms.

• Heme & Hemoglobin

  • Bilirubin formation and excretion/catabolism of Heme: Detailed explanation. This is a very common SE or LE.

  • Jaundice: Types (hemolytic, hepatocellular, obstructive), biochemical alterations in blood and urine, laboratory findings, and differential diagnosis. Frequently presented as LEs or SEs with case studies.

  • Heme synthesis and its regulation.

  • Porphyrias: Definition, classification, salient features, and specific focus on acute intermittent porphyria. This is a recurring SN or SA question.

• Function Tests

  • Renal Function Tests: Classification, detail on clearance tests (e.g., Creatinine clearance) and their clinical significance. This is a highly recurring topic, often as an SE or SA.

  • Thyroid function tests and their significance.

• Genetics & Molecular Biology

  • Translation: Definition, steps involved, inhibitors, and post-translational modifications. This is an extremely common LE topic.

  • Transcription: Definition, steps (in prokaryotes and eukaryotes), inhibitors, and post-transcriptional modifications. Also an extremely common LE.

  • Polymerase Chain Reaction (PCR): Principle, applications (including in diagnosis of COVID-19), and significance. This is a very common SE or SN.

  • Tumor markers: Names, clinical relevance, oncogenes, and tumor suppressor genes. This is a very frequent SA or SN.

  • Genetic Code: Definition and salient features (e.g., degeneracy, wobble effect).

• Detoxification (Xenobiotics)

  • Detoxification reactions: Definition, phases (Phase I & II), and specific examples of detoxification by conjugation (e.g., glucuronic acid, amino acids used). This is a very common SE or SA topic.

• Free Radicals & Anti-oxidants

  • Antioxidants: Definition, classification (chain-breaking, preventive), and examples (antioxidant vitamins and enzymes). This is a frequent SE or SA.

• Immunology

  • Immunoglobulins: Types, structure, and functions. This is a highly significant LE or SE topic.

Other Important Questions:

• Nucleotide Chemistry & Metabolism: Orotic aciduria (enzyme defect), Two conditions of hyperuricemia.

• Acid-Base & Fluid-Electrolyte Balance: Electrolyte balance (normal levels of serum sodium, potassium, chloride), Hyperkalemia (causes, significance), Anion gap.

• Heme & Hemoglobin: Hemoglobinopathies (Molecular basis and diagnosis of Sickle cell anemia and Thalassemia), Van den Bergh test.

• Function Tests: Renal clearance tests (Creatinine clearance definition), Microalbuminuria, Thyroid function tests.

• Genetics & Molecular Biology: DNA Replication (principles, stages, inhibitors, DNA repair mechanisms), Recombinant DNA technology (applications, vectors), Genetic Code (features like degeneracy, wobble effect), Oncogenes and tumor suppressor genes, Blotting techniques (Southern, Western), Mutation (types, causes).

• Extracellular Matrix: Collagen (structure, functions), Keratin, Prion disease, Contractile proteins, Elastin.

• Immunology: Active vs. passive immunity, Monoclonal antibodies.

• Laboratory Tests: Electrophoresis (principle, applications, A/G ratio), ELISA (principle, applications), Glucose Tolerance Test (GTT: indications, responses), C-peptide.

Key for Answering 2-Mark Questions (Consolidated & Expanded)

I. Proteins, Amino Acids & Enzymes

1. Plasma Transport Proteins

   • Years: Sep 2011, Aug 2013

   • Question: Name two plasma transport proteins and mention their role.

   • Key:

     • Albumin: It is the most abundant plasma protein. It transports various substances including free fatty acids, bilirubin, calcium, and many drugs. It is a non-specific transporter.

     • Transferrin: This is the specific transport protein for iron. It transports iron safely in the ferric (Fe³⁺) state from the sites of absorption and storage to the bone marrow for hemoglobin synthesis.

2. Functions of Albumin

   • Years: Mar 2012

   • Question: Mention four functions of albumin.

   • Key:

     • Maintains Colloid Osmotic Pressure: Albumin is responsible for ~80% of the plasma's osmotic pressure, which holds fluid within the capillaries.

     • Transport: It acts as a non-specific carrier for substances like fatty acids, bilirubin, hormones, calcium, and drugs.

     • Nutritional Role: It serves as a source of amino acids for tissues during protein deprivation.

     • Buffering Action: Albumin has a minor role in buffering the blood pH due to its ionizable groups.

3. Albumin-Globulin (A/G) Ratio

   • Years: Aug 2013, Jan 2018

   • Question: Mention the normal albumin-globulin ratio and a condition where it is reversed.

   • Key:

     • Normal Ratio: The normal A/G ratio is approximately 1.2:1 to 1.5:1 (or simply >1), as albumin is more abundant than globulins.

     • Reversal (<1) is seen in:

       1. Cirrhosis of the Liver: Decreased albumin synthesis by the damaged liver.

       2. Multiple Myeloma: Massive overproduction of monoclonal globulins (antibodies).

4. Ketogenic Amino Acids

   • Years: Aug 2013

   • Question: Mention ketogenic amino acids.

   • Key:

     • Definition: Amino acids whose carbon skeletons are degraded to form acetyl-CoA or acetoacetyl-CoA. These can be converted into ketone bodies but not glucose.

     • Exclusively Ketogenic: Leucine and Lysine.

5. Essential Amino Acids

   • Years: Aug 2019

   • Question: Enumerate essential amino acids.

   • Key:

     • Definition: Amino acids that cannot be synthesized by the human body and therefore must be supplied in the diet.

     • Examples: Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Leucine, Lysine. (Mnemonic: PVT TIM HALL).

6. Polyamines

   • Years: Feb 2014

   • Question: Name the polyamines and mention their functions.

   • Key:

     • Names: Spermidine and Spermine (synthesized from Putrescine).

     • Functions: They are positively charged molecules that bind to DNA and are essential for cell growth, proliferation, and differentiation.

7. Specialized Products of Tryptophan

   • Years: Feb 2016

   • Question: Mention specialized products of tryptophan.

   • Key:

     • Niacin (Vitamin B3): A small fraction of dietary tryptophan can be converted to niacin.

     • Serotonin: A neurotransmitter that regulates mood, appetite, and sleep.

     • Melatonin: A hormone synthesized in the pineal gland that regulates the sleep-wake cycle.

8. Sources of Ammonia

   • Years: Aug 2015

   • Question: Mention the sources of ammonia.

   • Key:

     • Transdeamination of Amino Acids: This is the major source, where amino groups are removed from amino acids, primarily in the liver.

     • Action of Intestinal Bacteria: Gut bacteria act on urea and undigested protein to produce ammonia.

     • Catabolism of Purines and Pyrimidines.

9. Proteolytic Enzymes

   • Years: Aug 2018

   • Question: Mention proteolytic enzymes.

   • Key:

     • Definition: Enzymes that catalyze the breakdown of proteins into smaller polypeptides or single amino acids by hydrolyzing peptide bonds.

     • Examples: Pepsin (in the stomach), Trypsin and Chymotrypsin (secreted by the pancreas into the small intestine).

10. Exopeptidases

    • Years: Jan 2019

    • Question: What are exopeptidases and mention examples.

    • Key:

      • Definition: Proteolytic enzymes that cleave peptide bonds at the terminal ends of a polypeptide chain.

      • Examples: Carboxypeptidases (which cleave from the C-terminus) and Aminopeptidases (which cleave from the N-terminus).

11. Protein Denaturation

    • Years: Mar 2021

    • Question: Define protein denaturation.

    • Key:

      • Definition: The process by which a protein loses its native three-dimensional structure (secondary, tertiary, and quaternary) due to disruption of weak non-covalent bonds like hydrogen bonds and hydrophobic interactions.

      • Effect: This leads to a loss of the protein's biological function. The primary structure (peptide bonds) remains intact.

12. Non-Covalent Bonds in Protein Structure

    • Years: Aug 2019

    • Question: Name the non-covalent bonds responsible for protein structure.

    • Key:

      • Hydrogen Bonds: Crucial for stabilizing secondary structures like α-helices and β-sheets.

      • Hydrophobic Interactions: The tendency of nonpolar side chains to cluster together in the protein's interior.

      • Ionic Bonds (Salt Bridges): Formed between oppositely charged side chains.

      • Van der Waals Forces: Weak, short-range attractions between all atoms.

13. Isoelectric pH (pI)

    • Years: Aug 2013, Jan 2020, Aug 2015

    • Question: Define isoelectric pH and state the properties of a protein at its isoelectric pH.

    • Key:

      • Definition: The specific pH at which a molecule (like a protein) has a net electrical charge of zero.

      • Properties at pI: At this pH, the protein has minimum solubility (and may precipitate out of solution) and does not migrate in an electric field.

14. Km value

    • Years: Feb 2014, Feb 2015, Aug 2018

    • Question: Define Km value and state its importance/significance.

    • Key:

      • Definition: The Michaelis constant (Km) is numerically equal to the substrate concentration at which the reaction velocity is half of its maximum value (Vmax).

      • Significance: It is an inverse measure of the affinity of an enzyme for its substrate. A low Km indicates high affinity, while a high Km indicates low affinity.

15. Optimum pH of Enzymes

    • Years: Mar 2012

    • Question: Define optimum pH and give one example.

    • Key:

      • Definition: The specific pH at which an enzyme exhibits its maximum catalytic activity. Extreme changes in pH can cause denaturation and loss of function.

      • Examples: Pepsin (in the stomach) has an optimum pH of 1.5–2.5. Trypsin (in the small intestine) has an optimum pH of ~8.0.

16. Allosteric Enzymes

    • Years: Aug 2015

    • Question: Define allosteric enzymes.

    • Key:

      • Definition: Enzymes that possess a regulatory site (the allosteric site) in addition to their active site.

      • Mechanism: The binding of a modulator (activator or inhibitor) to the allosteric site causes a conformational change that alters the enzyme's catalytic activity.

17. Isomerases

    • Years: Mar 2012

    • Question: What are isomerases and give an example indicating the reaction catalysed?

    • Key:

      • Definition: Isomerases are a class of enzymes that catalyze the structural rearrangement of isomers (molecules with the same chemical formula but different atomic arrangements).

      • Example: The enzyme Phosphohexose Isomerase catalyzes the interconversion of Glucose-6-phosphate and Fructose-6-phosphate in the glycolysis pathway.

18. Pro-enzymes (Zymogens)

    • Years: Aug 2016

    • Question: Define pro-enzymes.

    • Key:

      • Definition: Inactive precursors of enzymes. They require a specific biochemical change, such as proteolytic cleavage, to become active enzymes.

      • Significance: This mechanism prevents the enzyme from causing damage at the site of its synthesis. For example, pepsinogen is safely produced in stomach cells and is only activated to the digestive enzyme pepsin in the stomach lumen.

19. Enzyme Specificity

    • Years: Aug 2019

    • Question: Mention the types of specificity of enzymes.

    • Key:

      • Absolute Specificity: The enzyme acts on only one specific substrate (e.g., Urease acts only on urea).

      • Group Specificity: The enzyme acts on a group of structurally similar substrates (e.g., Pepsin cleaves peptide bonds adjacent to aromatic amino acids).

      • Stereospecificity: The enzyme acts on only one stereoisomer of a substrate (e.g., L-amino acid oxidase acts only on L-amino acids).

20. Uncouplers of Oxidative Phosphorylation

    • Years: Aug 2012, Feb 2016, Jan 2019

    • Question: What are uncouplers of oxidative phosphorylation? Give examples.

    • Key:

      • Definition: Uncouplers are chemical agents or proteins that disrupt the coupling between the electron transport chain (ETC) and ATP synthesis. They dissipate the proton gradient across the inner mitochondrial membrane, allowing electron transport to continue without producing ATP.

      • Examples: 2,4-Dinitrophenol (DNP) (a synthetic chemical) and Thermogenin (uncoupling protein-1, UCP1) found in brown adipose tissue.

21. Substrate-Level Phosphorylation

    • Years: Feb 2013, Aug 2016, Aug 2018

    • Question: What is substrate-level phosphorylation? Mention examples.

    • Key:

      • Definition: The direct synthesis of ATP (or GTP) by transferring a high-energy phosphate group from a substrate molecule to ADP (or GDP). This process does not involve the electron transport chain.

      • Examples:

        1. Conversion of Phosphoenolpyruvate to Pyruvate in glycolysis.

        2. Conversion of 1,3-Bisphosphoglycerate to 3-Phosphoglycerate in glycolysis.

        3. Conversion of Succinyl-CoA to Succinate in the TCA cycle (produces GTP).

II. Carbohydrates, Lipids & Metabolism

1. Epimers

   • Years: Mar 2012, Aug 2013, Mar 2021

   • Question: Define epimers and give two examples.

   • Key:

     • Definition: Epimers are carbohydrate isomers (monosaccharides) that differ in their configuration around only one specific carbon atom.

     • Examples:

       1. Glucose and Galactose are C-4 epimers.

       2. Glucose and Mannose are C-2 epimers.

2. Invert Sugar

   • Years: Aug 2016

   • Question: What is invert sugar?

   • Key:

     • Definition: An equimolar mixture of glucose and fructose.

     • Formation: It is produced by the enzymatic (invertase) or acidic hydrolysis of sucrose. The name "invert" comes from the change in optical rotation from dextrorotatory (+) for sucrose to levorotatory (-) for the mixture.

3. Cori's Cycle

   • Years: Feb 2017, Nov 2020

   • Question: What is Cori's cycle?

   • Key:

     • Definition: A metabolic pathway that links anaerobic glycolysis in muscles with gluconeogenesis in the liver.

     • Process: Lactate, produced in muscles during strenuous exercise, is transported via the blood to the liver. The liver converts the lactate back into glucose, which can then return to the muscles to be used for energy or stored as glycogen.

4. HMP Shunt Significance

   • Years: Aug 2012, Aug 2015, Jan 2018

   • Question: Mention the significance of the HMP shunt pathway.

   • Key:

     • Production of NADPH: This is crucial for reductive biosynthesis (e.g., fatty acid and steroid synthesis) and for antioxidant defense, as it is required to regenerate reduced glutathione.

     • Production of Ribose-5-phosphate: This pentose sugar is an essential precursor for the synthesis of nucleotides (ATP, GTP) and nucleic acids (DNA, RNA).

5. Rapaport-Leubering Cycle

   • Years: Feb 2014, Feb 2016

   • Question: List the functions of the Rapaport-Leubering cycle.

   • Key:

     • Location: A shunt pathway in glycolysis that occurs specifically in red blood cells (RBCs).

     • Function: Its primary function is to produce 2,3-Bisphosphoglycerate (2,3-BPG). 2,3-BPG binds to deoxyhemoglobin, decreases its affinity for oxygen, and facilitates the release of oxygen to peripheral tissues.

6. Functions of Cholesterol

   • Years: Aug 2012, Feb 2013

   • Question: Mention four functions of cholesterol.

   • Key:

     • Cell Membrane Structure: It is a vital component of cell membranes, where it modulates fluidity.

     • Precursor for Bile Acids: It is converted to bile acids in the liver, which are essential for fat digestion.

     • Precursor for Steroid Hormones: It is the precursor for all steroid hormones, including glucocorticoids, mineralocorticoids, and sex hormones.

     • Precursor for Vitamin D: It is converted to 7-dehydrocholesterol, which is then converted to Vitamin D in the skin upon exposure to UV light.

7. Regulation of Cholesterol Synthesis

   • Years: Aug 2013

   • Question: Explain the regulation of cholesterol synthesis.

   • Key:

     • The key regulatory and rate-limiting enzyme is HMG-CoA Reductase.

     • Regulation Mechanisms:

       1. Feedback Inhibition: High levels of intracellular cholesterol inhibit the enzyme.

       2. Hormonal Regulation: Insulin upregulates the enzyme, while glucagon downregulates it.

       3. Drug Inhibition: Statin drugs act as competitive inhibitors of HMG-CoA Reductase.

8. LDL Receptor

   • Years: Aug 2013

   • Question: What is the LDL receptor?

   • Key:

     • Definition: A cell-surface receptor protein that recognizes and binds to Low-Density Lipoprotein (LDL) particles in the blood.

     • Function: It mediates the endocytosis (uptake) of LDL into the cell, which delivers cholesterol to peripheral tissues. A defect in this receptor causes Familial Hypercholesterolemia.

9. Reverse Cholesterol Transport

   • Years: Jan 2018

   • Question: What is reverse cholesterol transport?

   • Key:

     • Definition: The process of transporting excess cholesterol from peripheral tissues back to the liver for excretion.

     • Mediator: This crucial pathway is primarily mediated by High-Density Lipoprotein (HDL), often referred to as "good cholesterol."

10. Lipotropic Factors

    • Years: Feb 2013, Jan 2020, Nov 2020

    • Question: What are lipotropic factors? Name any two.

    • Key:

      • Definition: Substances that prevent the accumulation of excess fat in the liver, a condition known as fatty liver or steatosis.

      • Examples: Choline and Methionine. They are essential for the synthesis of phospholipids required for the transport of triglycerides out of the liver as VLDL.

11. Functions of Phospholipids

    • Years: Feb 2014, Jul 2017, Nov 2020

    • Question: Mention four functions of phospholipids.

    • Key:

      • Structural Components: They are the main building blocks of all biological membranes, forming the lipid bilayer.

      • Lung Surfactant: Dipalmitoylphosphatidylcholine (Lecithin) is the major component, preventing alveolar collapse.

      • Signal Transduction: Phosphatidylinositol is a precursor for second messengers like IP3 and DAG.

      • Emulsification: They aid in the digestion and absorption of dietary fats.

12. Role of Bile Salts

    • Years: Feb 2015

    • Question: What is the role of bile salts in fat digestion and absorption?

    • Key:

      • Emulsification: Bile salts are amphipathic molecules that break down large dietary fat globules into smaller, microscopic micelles.

      • Increased Surface Area: This emulsification process vastly increases the surface area available for the digestive enzyme pancreatic lipase to act upon, allowing for efficient fat digestion and absorption.

13. Role of Carnitine

    • Years: Aug 2015

    • Question: Explain the role of carnitine.

    • Key:

      • Function: Carnitine is essential for the transport of long-chain fatty acids from the cytoplasm into the mitochondrial matrix, where they undergo β-oxidation for energy production.

      • Mechanism: This process, known as the carnitine shuttle, is a rate-limiting step in fatty acid oxidation.

14. TCA Cycle Amphibolic Nature

    • Years: Feb 2013

    • Question: Why is the TCA cycle called amphibolic?

    • Key:

      • The TCA cycle is described as amphibolic because it participates in both catabolism (breaking down molecules) and anabolism (building up molecules).

      • Catabolic Role: It oxidizes acetyl-CoA to CO₂ and H₂O, producing energy (ATP, NADH, FADH₂).

      • Anabolic Role: Its intermediates are used as precursors for biosynthesis (e.g., citrate for fatty acids, α-ketoglutarate for amino acids).

15. Anaplerotic Role of TCA Cycle

    • Years: Jan 2019

    • Question: What is the anaplerotic role of the TCA cycle?

    • Key:

      • Definition: Anaplerotic reactions are those that replenish the intermediates of the TCA cycle that have been removed for biosynthetic purposes.

      • Example: The most important anaplerotic reaction is the conversion of Pyruvate to Oxaloacetate, catalyzed by the enzyme pyruvate carboxylase.

III. Inborn Errors of Metabolism & Clinical Conditions

1. Glycogen Storage Diseases (GSDs)

   • Years: Sep 2011

   • Question: Mention two glycogen storage diseases with their deficient enzyme.

   • Key:

     • Von Gierke's Disease (Type I): Caused by a deficiency of Glucose-6-phosphatase. Characterized by severe fasting hypoglycemia.

     • McArdle's Disease (Type V): Caused by a deficiency of Muscle Glycogen Phosphorylase. Characterized by exercise-induced muscle cramps and fatigue.

2. Cori's Disease (GSD Type III)

   • Years: Mar 2012, Jul 2017

   • Question: What is Cori's disease and mention the enzyme defect in it?

   • Key:

     • Definition: A glycogen storage disease (Type III) where abnormal glycogen with short outer branches accumulates.

     • Enzyme Defect: Amylo-1,6-glucosidase (debranching enzyme). It leads to mild hypoglycemia and hepatomegaly.

3. Von Gierke's Disease (GSD Type I)

   • Years: Aug 2016, Mar 2021

   • Question: Describe Von Gierke's disease.

   • Key:

     • Definition: A glycogen storage disease (Type I) caused by a deficiency of the enzyme Glucose-6-phosphatase.

     • Features: This enzyme is required for both gluconeogenesis and glycogenolysis. Its absence leads to severe fasting hypoglycemia, lactic acidosis, hyperuricemia, and hepatomegaly.

4. Phenylketonuria (PKU)

   • Years: Feb 2015, Feb 2016

   • Question: What is phenylketonuria and name the enzymatic defect/abnormal metabolites?

   • Key:

     • Definition: An inborn error of metabolism where the body cannot convert the amino acid phenylalanine to tyrosine.

     • Enzyme Defect: Phenylalanine hydroxylase.

     • Abnormal Metabolites: Leads to the accumulation of phenylalanine and its byproducts (phenylpyruvate, phenylacetate) in the blood and urine, causing a "mousy" odor and severe intellectual disability if untreated.

5. Hartnup's Disease

   • Years: Aug 2012, Aug 2014

   • Question: What is Hartnup's disease?

   • Key:

     • Definition: An autosomal recessive disorder caused by a defect in the transporter for neutral amino acids (like Tryptophan) in the small intestine and kidneys.

     • Features: Leads to decreased absorption and increased excretion of these amino acids. The lack of tryptophan results in niacin deficiency, causing pellagra-like symptoms (dermatitis, diarrhea, dementia).

6. Alkaptonuria

   • Years: Aug 2014, Jul 2017

   • Question: What is Alkaptonuria?

   • Key:

     • Definition: An inborn error of tyrosine metabolism.

     • Enzyme Defect: Deficiency of the enzyme homogentisate oxidase.

     • Features: This leads to the accumulation of homogentisic acid, which causes urine to turn dark on standing, and ochronosis (dark pigmentation of cartilage and connective tissues), leading to arthritis.

7. Albinism

   • Years: Aug 2013, Feb 2017

   • Question: What is Albinism?

   • Key:

     • Definition: A group of inherited disorders characterized by a complete or partial absence of melanin pigment in the skin, hair, and eyes.

     • Enzyme Defect: The most common form is caused by a deficiency of the enzyme Tyrosinase, which is required for melanin synthesis from tyrosine.

8. Gaucher's Disease

   • Years: Sep 2011

   • Question: What is Gaucher's disease? Mention two clinical features.

   • Key:

     • Definition: A lysosomal storage disease caused by a deficiency of the enzyme Glucocerebrosidase. This leads to the accumulation of the lipid glucocerebroside in macrophages.

     • Clinical Features:

       1. Hepatosplenomegaly (massive enlargement of the liver and spleen).

       2. Bone abnormalities, including bone pain and fractures. Anemia and thrombocytopenia are also common.

9. Tay-Sachs Disease

   • Years: Aug 2016

   • Question: Mention the enzyme deficient in Tay-Sachs disease.

   • Key:

     • Definition: A devastating lysosomal storage disease that causes progressive neurodegeneration.

     • Enzyme Defect: Deficiency of the enzyme Hexosaminidase A, leading to the accumulation of GM2 gangliosides in the brain.

10. Lesch-Nyhan Syndrome & Orotic Aciduria Enzyme Defects

    • Years: Feb 2014

    • Question: Mention the enzyme defect in Lesch-Nyhan syndrome and orotic aciduria.

    • Key:

      • Lesch-Nyhan Syndrome: Deficiency of HGPRT (Hypoxanthine-Guanine Phosphoribosyltransferase) in the purine salvage pathway.

      • Orotic Aciduria: Deficiency of UMP Synthase (orotate phosphoribosyltransferase and OMP decarboxylase activities) in the pyrimidine synthesis pathway.

11. Orotic Aciduria

    • Years: Aug 2013

    • Question: What is orotic aciduria?

    • Key:

      • Definition: A rare inherited disorder of pyrimidine synthesis.

      • Cause & Features: Caused by a deficiency of UMP Synthase, it leads to poor growth, megaloblastic anemia, and the excretion of large amounts of orotic acid in the urine.

12. Wilson's Disease

    • Years: Sep 2011, Feb 2013, Aug 2016

    • Question: What is Wilson's disease?

    • Key:

      • Definition: An autosomal recessive disorder of copper metabolism.

      • Cause: Caused by a mutation in the gene for copper-transporting ATPase (ATP7B), which impairs copper excretion into bile and its incorporation into ceruloplasmin.

      • Features: Copper accumulates in the liver, brain, and eyes, leading to liver disease, neurological symptoms, and characteristic Kayser-Fleischer rings in the cornea.

13. Metabolic Acidosis

    • Years: Sep 2011, Feb 2013

    • Question: What is metabolic acidosis? Give one example of a disease associated with it.

    • Key:

      • Definition: An acid-base disorder characterized by a primary decrease in plasma bicarbonate (HCO₃⁻) concentration, resulting in a low blood pH (<7.35).

      • Example: Diabetic Ketoacidosis (DKA), where the overproduction of acidic ketone bodies consumes bicarbonate, leading to a high anion gap metabolic acidosis.

14. Respiratory Acidosis

    • Years: Jan 2018

    • Question: What is respiratory acidosis and mention one example.

    • Key:

      • Definition: An acid-base disorder caused by hypoventilation (inadequate removal of CO₂ by the lungs). This leads to an increase in blood pCO₂ (hypercapnia) and a decrease in blood pH.

      • Example: Chronic Obstructive Pulmonary Disease (COPD) or severe asthma.

15. Post-Hepatic Jaundice

    • Years: Sep 2011, Feb 2013

    • Question: What is post-hepatic jaundice? How is it diagnosed biochemically?

    • Key:

      • Definition: Jaundice caused by an obstruction of the biliary tract, which prevents the flow of conjugated bilirubin from the liver to the intestine.

      • Biochemical Diagnosis:

        1. Markedly elevated serum conjugated (direct) bilirubin.

        2. Markedly elevated serum Alkaline Phosphatase (ALP).

        3. Presence of bilirubin and bile salts in the urine.

16. Pellagra

    • Years: Mar 2012, Aug 2019

    • Question: Mention the cause and clinical features of pellagra.

    • Key:

      • Cause: A systemic disease caused by a severe deficiency of Niacin (Vitamin B3) or its precursor, tryptophan.

      • Clinical Features: The classic "3 Ds": Dermatitis (a photosensitive, pigmented rash), Diarrhea, and Dementia.

17. Gout

    • Years: Mar 2012, Aug 2013, Jan 2020

    • Question: What is gout? Mention clinical features and drugs used to treat it.

    • Key:

      • Definition: A form of inflammatory arthritis caused by hyperuricemia (high levels of uric acid in the blood) and the subsequent deposition of monosodium urate crystals in joints and tissues.

      • Features: Recurrent attacks of severe pain, swelling, and redness, typically affecting the big toe (podagra).

      • Drugs: Allopurinol (inhibits uric acid synthesis), Colchicine (anti-inflammatory), and NSAIDs.

18. Thalassemia

    • Years: Aug 2012

    • Question: Define thalassemia and mention the different types.

    • Key:

      • Definition: A group of inherited hemolytic anemias characterized by a defect in the synthesis of one or more globin chains of hemoglobin.

      • Types:

        1. Alpha (α)-thalassemia: Caused by deficient synthesis of α-globin chains.

        2. Beta (β)-thalassemia: Caused by deficient synthesis of β-globin chains.

19. Abnormal Hemoglobins

    • Years: Mar 2021

    • Question: List two clinical conditions of abnormal hemoglobin.

    • Key:

      • Sickle Cell Anemia: Caused by Hemoglobin S (HbS), where glutamic acid is replaced by valine in the β-chain. It leads to sickling of red blood cells and vaso-occlusive crises.

      • Hemoglobin C Disease: Caused by Hemoglobin C (HbC), where glutamic acid is replaced by lysine in the β-chain. It causes a mild chronic hemolytic anemia.

20. Bence Jones Protein

    • Years: Feb 2015

    • Question: What are Bence Jones proteins?

    • Key:

      • Definition: Monoclonal immunoglobulin light chains (either kappa or lambda) that are produced in excess by neoplastic plasma cells.

      • Significance: They are small enough to be filtered by the glomerulus and are found in the urine. Their presence is a hallmark of Multiple Myeloma.

IV. Vitamins & Minerals

1. Functions of Biotin (Vitamin B7)

   • Years: Aug 2012

   • Question: Mention the functions of biotin.

   • Key:

     • Coenzyme Role: Biotin acts as a coenzyme for carboxylation reactions, where it functions as a carrier of activated CO₂.

     • Key Reactions: It is essential for enzymes like Pyruvate carboxylase (in gluconeogenesis) and Acetyl-CoA carboxylase (in fatty acid synthesis).

2. Functions of Thiamine (Vitamin B1)

   • Years: Feb 2016

   • Question: Mention the biochemical functions of thiamine.

   • Key:

     • Active Form: Thiamine's active coenzyme form is Thiamine Pyrophosphate (TPP).

     • Functions: TPP is a crucial coenzyme for key enzymes in carbohydrate metabolism, including:

       1. Pyruvate Dehydrogenase Complex (links glycolysis to the TCA cycle).

       2. α-Ketoglutarate Dehydrogenase Complex (in the TCA cycle).

       3. Transketolase (in the HMP shunt).

3. Role of Thiamine Pyrophosphate (TPP)

   • Years: Aug 2019, Jan 2019

   • Question: What is the biochemical role/functions of thiamine pyrophosphate?

   • Key: (Same as Q.58)

4. Folate Antagonists

   • Years: Feb 2014

   • Question: What are folate antagonists?

   • Key:

     • Definition: Drugs that interfere with the function of folic acid, typically by inhibiting the enzyme dihydrofolate reductase.

     • Example & Use: Methotrexate is a folate antagonist used in cancer chemotherapy and as an immunosuppressant because it blocks DNA synthesis in rapidly dividing cells.

5. Folate Trap

   • Years: Feb 2015, Aug 2019

   • Question: What is the folate trap?

   • Key:

     • Definition: A condition that occurs in Vitamin B12 deficiency.

     • Mechanism: Folic acid gets metabolically "trapped" as N5-methyltetrahydrofolate because the B12-dependent enzyme methionine synthase is required to remove the methyl group. This leads to a functional folate deficiency, causing megaloblastic anemia.

6. Function & Deficiency of Vitamin E

   • Years: Feb 2017

   • Question: Mention the function and deficiency manifestations of vitamin E.

   • Key:

     • Function: Vitamin E (tocopherol) is the major lipid-soluble antioxidant in the body. It protects cell membranes, particularly polyunsaturated fatty acids (PUFAs), from damage by free radicals.

     • Deficiency: Rare in humans, but can lead to hemolytic anemia (due to increased RBC fragility) and neurological symptoms.

7. Functions of Vitamin K

   • Years: Aug 2016

   • Question: Mention the functions of vitamin K.

   • Key:

     • Coenzyme Role: Vitamin K acts as a coenzyme for the enzyme gamma-glutamyl carboxylase.

     • Function: This enzyme catalyzes the post-translational gamma-carboxylation of glutamic acid residues in several blood clotting factors (II, VII, IX, X), which is essential for their activation and ability to bind calcium.

8. Functions of Magnesium

   • Years: Aug 2016

   • Question: Mention the functions of magnesium.

   • Key:

     • Enzyme Cofactor: Magnesium is a cofactor for over 300 enzymes, especially kinases and other enzymes that involve ATP, as it helps stabilize the negative charges on the phosphate groups.

     • Neuromuscular Function: It is essential for normal muscle contraction and nerve impulse transmission.

9. Role of Zinc

   • Years: Jan 2020

   • Question: What is the role of zinc?

   • Key:

     • Enzyme Cofactor: Zinc is a vital cofactor for a wide range of enzymes, including carbonic anhydrase and alcohol dehydrogenase.

     • Structural Role: It is a component of "zinc finger" motifs in transcription factors, allowing them to bind to DNA. It is also crucial for wound healing and immune function.

10. Factors Affecting Iron Absorption

    • Years: Aug 2013, Jul 2017

    • Question: Mention factors affecting/influencing iron absorption.

    • Key:

      • Enhancers: Vitamin C (Ascorbic acid) enhances absorption by reducing ferric iron (Fe³⁺) to the more soluble ferrous iron (Fe²⁺). An acidic pH in the stomach also aids absorption.

      • Inhibitors: Phytates (found in cereals and grains) and Tannins (found in tea and coffee) chelate iron and reduce its bioavailability.

11. Transport of Iron

    • Years: Jan 2019

    • Question: How is iron transported?

    • Key:

      • Iron is transported in the bloodstream bound to a specific plasma protein called transferrin.

      • Transferrin binds to ferric iron (Fe³⁺) and delivers it to cells throughout the body, particularly to the bone marrow for hemoglobin synthesis.

V. Molecular Biology & Genetics

1. Point Mutation

   • Years: Aug 2012

   • Question: Define point mutation.

   • Key:

     • Definition: A genetic mutation where a single nucleotide base is changed, inserted, or deleted from a sequence of DNA or RNA.

     • Types: Substitution (missense, nonsense, silent), Insertion, and Deletion.

2. Effects of Mutation

   • Years: Jan 2019

   • Question: What are the effects of mutation?

   • Key:

     • Mutations can have various effects on the resulting protein:

       1. Loss of Function: The protein may become non-functional or have reduced activity.

       2. Gain of Function: The protein may acquire a new or enhanced activity.

       3. No Effect (Silent Mutation): The mutation may not change the amino acid sequence or the protein's functio

     • These effects can lead to genetic diseases or provide the basis for evolution.

3. Wobble Hypothesis (See Q.58)

4. Base-Pairing Rule

   • Years: Jan 2018

   • Question: What is the base-pairing rule?

   • Key:

     • Also known as Chargaff's rule, it describes the specific pairing of nitrogenous bases in DNA.

     • Rule: Adenine (A), a purine, always pairs with Thymine (T), a pyrimidine, via two hydrogen bonds. Guanine (G), a purine, always pairs with Cytosine (C), a pyrimidine, via three hydrogen bonds.

5. Genetic Code

   • Years: Aug 2012, Nov 2020

   • Question: Define genetic code.

   • Key:

     • Definition: The set of rules used by living cells to translate the information encoded within genetic material (DNA or mRNA sequences) into proteins.

     • Features: It is a triplet code (a sequence of three nucleotides, called a codon, specifies one amino acid), degenerate (most amino acids are coded by more than one codon), and nearly universal.

6. Unusual Bases in tRNA

   • Years: Mar 2012

   • Question: Mention a few unusual bases and where they are present.

   • Key:

     • These are modified purine or pyrimidine bases found primarily in transfer RNA (tRNA) that are created post-transcriptionally.

     • Examples: Dihydrouracil is found in the D-loop of tRNA, and Pseudouridine is found in the TΨC loop.

7. Spliceosomes

   • Years: Jan 2018

   • Question: Mention the function of spliceosomes.

   • Key:

     • Definition: Large and complex molecular machines found in the nucleus of eukaryotic cells.

     • Function: They assemble on pre-mRNA and carry out splicing, which is the process of removing non-coding regions called introns and joining the coding regions called exons to produce mature mRNA.

8. Post-Translational Modifications

   • Years: Feb 2017

   • Question: What are post-translational modifications?

   • Key:

     • Definition: The covalent and enzymatic modification of proteins following protein biosynthesis. These modifications are crucial for the protein's function, stability, and localization.

     • Examples: Phosphorylation (to activate/deactivate enzymes), Glycosylation (adding sugars for stability and targeting), and Hydroxylation (e.g., of proline and lysine in collagen).

9. Post-Transcriptional Modifications

   • Years: Jul 2017

   • Question: What are post-transcriptional modifications?

   • Key:

     • Definition: The chemical modifications that a primary RNA transcript (pre-mRNA) undergoes in eukaryotes to become a mature, functional RNA molecule.

     • Key Processes:

       1. 5' Capping: Addition of a 7-methylguanosine cap to the 5' end.

       2. 3' Polyadenylation: Addition of a poly-A tail to the 3' end.

       3. Splicing: Removal of introns.

10. Oncogenes

    • Years: Feb 2014, Jan 2018

    • Question: What are oncogenes?

    • Key:

      • Definition: Genes that have the potential to cause cancer. They are typically mutated versions of normal genes called proto-oncogenes, which regulate cell growth and differentiation.

      • Mechanism: The mutation leads to a protein that is overactive or produced in excess, driving uncontrolled cell proliferation. Examples: Ras, Myc.

11. Tumor Suppressor Genes

    • Years: Aug 2012

    • Question: Name two tumor suppressor genes.

    • Key:

      • Definition: Genes that create proteins that slow down cell division, repair DNA mistakes, or tell cells when to die (apoptosis). When they don't work properly, cells can grow out of control, which can lead to cancer.

      • Examples: p53 (the "guardian of the genome") and the Retinoblastoma (Rb) gene.

12. Tumor Markers

    • Years: Jan 2019

    • Question: What are tumor markers?

    • Key:

      • Definition: Substances, often proteins, that are produced by cancer cells or by the body in response to cancer. Their levels can be measured in the blood, urine, or body tissues.

      • Use: They are used for cancer screening, diagnosis, and monitoring the effectiveness of treatment. Examples: PSA (prostate cancer), AFP (liver cancer).

13. Apoptosis

    • Years: Jul 2017

    • Question: Define apoptosis.

    • Key:

      • Definition: Programmed cell death, often referred to as "cellular suicide."

      • Characteristics: It is a highly regulated and orderly process involving cell shrinkage, chromatin condensation, and formation of apoptotic bodies, which are then phagocytosed. Unlike necrosis, it does not elicit an inflammatory response.

14. Gene Therapy

    • Years: Nov 2020

    • Question: What is gene therapy?

    • Key:

      • Definition: A medical approach that treats or prevents disease by correcting the underlying genetic problem.

      • Mechanism: It typically involves introducing a new, correct copy of a gene into a patient's cells to replace a faulty, disease-causing gene, or by inactivating a mutated gene that is functioning improperly.

15. Recombinant DNA Technology Applications

    • Years: Aug 2016

    • Question: Mention four applications of recombinant DNA technology.

    • Key:

      • Production of Therapeutic Proteins: Manufacturing human proteins like insulin, growth hormone, and clotting factors in bacteria or yeast.

      • Development of Vaccines: Creating safer and more effective vaccines (e.g., Hepatitis B vaccine).

      • Diagnosis of Diseases: Developing diagnostic tests for genetic disorders and infectious diseases (e.g., PCR tests).

      • Agriculture: Creating genetically modified crops (GMOs) with improved traits like pest resistance or higher nutritional value.

16. DNA Fingerprinting

    • Years: Aug 2013

    • Question: What is DNA fingerprinting?

    • Key: (See Q.38)

17. Blotting Techniques (Southern & Western)

    • Years: Jul 2017, Feb 2017

    • Question: What are the Southern blot and Western blot techniques?

    • Key:

      • Southern Blotting: A technique used to detect a specific DNA sequence in a DNA sample. It involves separating DNA fragments by electrophoresis and identifying the target sequence with a labeled probe.

      • Western Blotting: A technique used to detect a specific protein in a sample. It involves separating proteins by electrophoresis and identifying the target protein with a specific antibody.

VI. Clinical & Analytical Biochemistry

1. ELISA (Enzyme-Linked Immunosorbent Assay)

   • Years: Feb 2014

   • Question: What is ELISA?

   • Key: (See Q.68)

2. Radioimmunoassay (RIA)

   • Years: Feb 2015

   • Question: What is the principle of radioimmunoassay?

   • Key: (See Q.90)

3. Serum Electrophoresis & Its Importance

   • Years: Nov 2020

   • Question: What is serum electrophoresis and its clinical importance?

   • Key:

     • Definition: A laboratory technique that separates the proteins in blood serum into distinct bands based on their size and electrical charge. The main fractions are albumin and globulins (alpha-1, alpha-2, beta, and gamma).

     • Clinical Importance: It is crucial for diagnosing conditions involving abnormal proteins, such as Multiple Myeloma, which shows a characteristic sharp monoclonal spike (M-band) in the gamma-globulin region.

4. Creatinine Clearance

   • Years: Aug 2014

   • Question: What is creatinine clearance?

   • Key: (See Q.60)

5. Urea Clearance Test

   • Years: Feb 2015

   • Question: What is the urea clearance test?

   • Key: (See Q.87)

6. Glomerular Function Tests

   • Years: Feb 2016

   • Question: Enumerate two glomerular function tests.

   • Key:

     • Estimation of Glomerular Filtration Rate (GFR): This is the best overall index of kidney function. It is commonly estimated using Creatinine Clearance.

     • Measurement of Serum Creatinine: An elevated serum creatinine level indicates impaired glomerular function.

7. Liver Function Tests (LFTs)

   • Years: Aug 2012

   • Question: Name the liver function tests.

   • Key: (See Q.18)

8. Diagnostic Enzymes in Liver Diseases

   • Years: Aug 2019

   • Question: Name four enzymes of diagnostic significance in liver diseases.

   • Key:

     • Alanine Transaminase (ALT): A sensitive marker for hepatocellular damage.

     • Aspartate Transaminase (AST): Another marker for hepatocellular damage.

     • Alkaline Phosphatase (ALP): A marker for cholestasis (bile duct obstruction).

     • Gamma-Glutamyl Transferase (GGT): A sensitive marker for cholestasis and alcohol-induced liver damage.

9. Clinical Significance of ALP

   • Years: Aug 2014

   • Question: What is the clinical significance of ALP?

   • Key: (See Q.54)

10. Detoxification by Conjugation

    • Years: Sep 2011, Feb 2013, Aug 2019

    • Question: Give two examples of detoxification by conjugation.

    • Key:

      • Definition: Phase II detoxification reactions where a xenobiotic or metabolite is made more water-soluble by conjugating it with an endogenous molecule.

      • Examples:

        1. Glucuronidation: Conjugation with glucuronic acid (e.g., detoxification of bilirubin).

        2. Sulfation: Conjugation with sulfate (e.g., detoxification of phenols).

11. Detoxification of Benzoic Acid & Sulfanilamide

    • Years: Aug 2015

    • Question: How are benzoic acid and sulfanilamide detoxified in the human body?

    • Key:

      • Benzoic Acid: Detoxified by conjugation with glycine to form hippuric acid, which is then excreted in the urine. This is a test of liver function.

      • Sulfanilamide: Primarily detoxified by acetylation (conjugation with an acetyl group).

12. Detoxification by Oxidation & Conjugation

    • Years: Feb 2016

    • Question: Give one example each of detoxification by oxidation and conjugation.

    • Key:

      • Oxidation (Phase I): The hydroxylation of aromatic compounds like benzene by the cytochrome P450 system to make them more reactive.

      • Conjugation (Phase II): The conjugation of bilirubin with glucuronic acid in the liver to form water-soluble bilirubin diglucuronide.

13. Detoxification by Reduction

    • Years: Aug 2016

    • Question: Mention two examples for detoxification by reduction.

    • Key:

      • Definition: A Phase I detoxification reaction where a xenobiotic is reduced, often making it more water-soluble or preparing it for Phase II.

      • Examples:

        1. The reduction of picric acid to picramic acid.

        2. The reduction of chloral hydrate to trichloroethanol.

14. Criteria to Diagnose Diabetes Mellitus

    • Years: Jan 2019

    • Question: What are the criteria to diagnose diabetes mellitus?

    • Key: (See Q.161 in previous detailed list)

15. Clinical Significance of Glycated Hemoglobin (HbA1c)

    • Years: Sep 2011, Jul 2017

    • Question: Write the clinical significance of glycated hemoglobin estimation.

    • Key: (See Q.3)

16. Insulin Receptor

    • Years: Jan 1900 (Note: this year is likely a typo in the source, but the question is valid)

    • Question: Describe the Insulin Receptor.

    • Key:

      • Type: The insulin receptor is a transmembrane receptor belonging to the receptor tyrosine kinase family.

      • Structure & Function: It consists of two alpha and two beta subunits. When insulin binds to the alpha subunits, it activates the tyrosine kinase activity of the beta subunits, leading to autophosphorylation and the initiation of intracellular signaling cascades.

VII. Integration, Bioenergetics & Miscellaneous

1. Buffer Systems in the Body
   * Years: Mar 2012
   * Question: Name the buffer systems in the body.
   * Key:

   • Bicarbonate Buffer System (H₂CO₃ / HCO₃⁻): The most important buffer system in the extracellular fluid (plasma). It is highly effective because its components can be regulated by the lungs (CO₂) and kidneys (HCO₃⁻).

   • Phosphate Buffer System (H₂PO₄⁻ / HPO₄²⁻): A major buffer system in the intracellular fluid and in urine, where its concentration is higher.

   • Protein Buffer System: Proteins, especially hemoglobin in red blood cells and albumin in plasma, act as buffers due to their ionizable amino acid side chains.

2. Chloride Shift
   * Years: Jan 2018
   * Question: What is the chloride shift?
   * Key:

   • Definition: An ionic exchange process that occurs across the red blood cell (RBC) membrane, also known as the Hamburger phenomenon.

   • Mechanism: In peripheral tissues, CO₂ enters RBCs and is converted to bicarbonate (HCO₃⁻). To maintain electrical neutrality, the HCO₃⁻ is transported out into the plasma in exchange for a chloride (Cl⁻) ion moving into the RBC. The process is reversed in the lungs.

3. Anion Gap
   * Years: Mar 2021
   * Question: Define the anion gap and mention its normal range.
   * Key:

   • Definition: The difference between the concentration of measured plasma cations (primarily Na⁺) and measured plasma anions (Cl⁻ and HCO₃⁻). It represents the concentration of unmeasured anions.

   • Formula & Range: Anion Gap = [Na⁺] – ([Cl⁻] + [HCO₃⁻]). The normal range is 8–16 mEq/L. An increased anion gap is a key feature of certain types of metabolic acidosis.

4. Distribution of Total Body Water
   * Years: Jan 2018
   * Question: Describe the distribution of total body water.
   * Key:

   • Total body water is divided into two major compartments:

   • Intracellular Fluid (ICF): The fluid within the cells, accounting for approximately two-thirds of the total body water.

   • Extracellular Fluid (ECF): The fluid outside the cells, accounting for the remaining one-third. The ECF is further subdivided into interstitial fluid and plasma.

5. Edema in Hypoalbuminemia
   * Years: Aug 2015
   * Question: Explain why edema develops in hypoalbuminemia.
   * Key:

   • Role of Albumin: Albumin is the primary determinant of colloid osmotic pressure (or oncotic pressure) in the plasma. This pressure is crucial for holding fluid within the blood vessels.

   • Mechanism of Edema: In hypoalbuminemia (low serum albumin), the colloid osmotic pressure decreases. This allows fluid to shift from the intravascular compartment into the interstitial space, leading to the accumulation of excess fluid in tissues, which is known as edema.

6. Antioxidants
   * Years: Nov 2020
   * Question: What are antioxidants?
   * Key:

   • Definition: Molecules that inhibit the oxidation of other molecules, thereby protecting cells from damage caused by free radicals and other reactive oxygen species (ROS).

   • Examples:

     1. Enzymatic: Superoxide dismutase, Catalase, Glutathione peroxidase.

     2. Non-enzymatic: Vitamin C, Vitamin E, Glutathione.

7. Biological Action of Glutathione
   * Years: Aug 2014, Feb 2017
   * Question: Mention the biological action of glutathione.
   * Key:

   • Major Antioxidant: In its reduced form (GSH), it is the most abundant intracellular antioxidant. It directly neutralizes free radicals and is a cofactor for the enzyme glutathione peroxidase.

   • Detoxification: It participates in Phase II detoxification by conjugating with drugs and xenobiotics, making them more water-soluble for excretion.

8. Immunoglobulin Classes & Function
   * Years: Aug 2015
   * Question: List the different classes of immunoglobulins and mention the functional role of any one.
   * Key:

   • Classes: The five main classes of immunoglobulins (antibodies) are IgG, IgA, IgM, IgD, and IgE.

   • Functional Role (Example: IgG): IgG is the most abundant immunoglobulin in the blood. It provides long-term immunity against pathogens, activates the complement system, and is the only class that can cross the placenta to provide passive immunity to the fetus.

9. Hypergammaglobulinemia Conditions
   * Years: Feb 2016
   * Question: Mention two clinical conditions of hypergammaglobulinemia.
   * Key:

   • Definition: A condition characterized by elevated levels of gamma globulins (antibodies) in the blood.

   • Conditions:

     1. Polyclonal Hypergammaglobulinemia: Seen in chronic infections (like tuberculosis), autoimmune diseases (like rheumatoid arthritis), and chronic liver disease.

     2. Monoclonal Hypergammaglobulinemia: A hallmark of Multiple Myeloma, where a single clone of plasma cells produces a massive amount of one specific antibody.

10. Primary Hyperoxaluria
    * Years: Jan 2018
    * Question: What is primary hyperoxaluria?
    * Key:

    • Definition: A group of rare, inherited metabolic disorders characterized by the overproduction of oxalate.

    • Consequence: The excess oxalate combines with calcium to form insoluble calcium oxalate crystals, which deposit in the kidneys and other tissues, leading to recurrent kidney stones, nephrocalcinosis, and progressive renal failure.

11. Fluorosis
    * Years: Jan 2018
    * Question: What is fluorosis?
    * Key:

    • Definition: A chronic condition caused by the excessive ingestion of fluoride.

    • Features: It primarily affects the teeth and bones. Dental fluorosis causes mottling and discoloration of tooth enamel. Skeletal fluorosis can lead to joint pain, stiffness, and bone deformities.

12. Beri-Beri
    * Years: Nov 2020
    * Question: What is Beri-Beri?
    * Key:

    • Cause: A disease caused by a severe deficiency of Thiamine (Vitamin B1).

    • Types:

      1. Dry Beri-Beri: Primarily affects the nervous system, causing peripheral neuropathy and muscle wasting.

      2. Wet Beri-Beri: Primarily affects the cardiovascular system, causing high-output cardiac failure and edema.

13. Dietary Fiber
    * Years: Feb 2015, Jan 2018
    * Question: What is dietary fiber?
    * Key:

    • Definition: The portion of plant-derived food that cannot be completely broken down by human digestive enzymes. It is a type of complex carbohydrate.

    • Functions: It adds bulk to the stool, promoting regular bowel movements (insoluble fiber), and can help lower cholesterol and blood sugar levels (soluble fiber).

14. Principles of Colorimetry
    * Years: Aug 2015
    * Question: What are the principles of colorimetry?
    * Key:

    • Colorimetry is a technique used to determine the concentration of a colored compound in a solution.

    • It is based on the Beer-Lambert Law, which states that the absorbance (A) of light by a solution is directly proportional to the concentration (c) of the absorbing substance and the path length (l) of the light through the solution (A = εcl).

15. Vanden Bergh Reaction
    * Years: Jan 2018
    * Question: What is the Vanden Bergh reaction?
    * Key:

    • Purpose: A chemical test used to differentiate between conjugated and unconjugated bilirubin in serum.

    • Reaction: It uses the Diazo reagent. Conjugated (direct) bilirubin is water-soluble and reacts immediately to form a colored product. Unconjugated (indirect) bilirubin is water-insoluble and requires an accelerator like methanol or caffeine to react.

16. Compare Starch and Glycogen
    * Years: Aug 2018
    * Question: Compare and contrast starch with glycogen.
    * Key:

    • Similarities: Both are storage polysaccharides composed of glucose units linked by glycosidic bonds.

    • Differences:

      1. Source: Starch is the storage form of glucose in plants, while glycogen is the storage form in animals.

      2. Structure: Glycogen is more highly branched than starch, which allows for more rapid mobilization of glucose when needed.

17. Active Methionine
    * Years: Aug 2014
    * Question: What is active methionine?
    * Key:

    • Name: S-Adenosylmethionine (SAM).

    • Function: It is formed from methionine and ATP. SAM is the body's primary methyl group donor and is essential for numerous transmethylation reactions, including the synthesis of creatine and epinephrine.

18. Calcitriol
    * Years: Aug 2014
    * Question: What is calcitriol?
    * Key:

    • Name: The hormonally active form of Vitamin D, also known as 1,25-dihydroxycholecalciferol.

    • Function: It functions as a steroid hormone to regulate calcium and phosphate homeostasis. Its primary action is to increase blood calcium levels by promoting absorption from the intestine, reabsorption from the kidney, and mobilization from bone.

19. Ceruloplasmin
    * Years: Jan 2018
    * Question: What is ceruloplasmin?
    * Key: (See Q.146)

Key for Answering 5-Mark Questions

I. Enzymes & Proteins

1. Enzyme Classification

   • Years: Sep 2011

   • Question: Define and classify enzymes. Give one example for each class and mention the reaction catalysed.

   • Key:

     1. Definition: Define enzymes as biological catalysts, typically proteins, that increase the rate of biochemical reactions without being consumed.

     2. Classification (IUBMB): List the 6 major classes with a brief description.

     3. Examples (One for each class):

        • Oxidoreductases: Lactate Dehydrogenase (Lactate ↔ Pyruvate).

        • Transferases: Alanine Transaminase (ALT) (Transfers amino group).

        • Hydrolases: Urease (Urea + H₂O → CO₂ + 2NH₃).

        • Lyases: Aldolase (Fructose-1,6-bisphosphate ↔ DHAP + G3P).

        • Isomerases: Phosphohexose Isomerase (Glucose-6-P ↔ Fructose-6-P).

        • Ligases: DNA Ligase (Joins DNA fragments).

2. Enzyme Inhibition

   • Years: Aug 2016

   • Question: Explain different types of enzyme inhibition giving suitable examples.

   • Key:

     1. Introduction: Define enzyme inhibition as the process where a substance (inhibitor) binds to an enzyme and decreases its activity.

     2. Competitive Inhibition:

        • Mechanism: Inhibitor resembles the substrate and competes for the active site. Can be overcome by increasing substrate concentration.

        • Effect on Kinetics: Increases Km, Vmax remains unchanged.

        • Example: Statin drugs inhibiting HMG-CoA reductase.

     3. Non-competitive Inhibition:

        • Mechanism: Inhibitor binds to a site other than the active site (allosteric site), changing the enzyme's conformation.

        • Effect on Kinetics: Decreases Vmax, Km remains unchanged.

        • Example: Lead inhibiting ALA dehydratase.

     4. Uncompetitive Inhibition: (Mention briefly) Binds only to the enzyme-substrate (ES) complex. Decreases both Vmax and Km.

3. Isoenzymes & Diagnostic Importance

   • Years: Jan 2018

   • Question: What are isoenzymes? Discuss the diagnostic importance of isoenzymes.

   • Key:

     1. Definition: Define isoenzymes (or isozymes) as different molecular forms of an enzyme that catalyze the same reaction but differ in their physical and chemical properties (like amino acid sequence, electrophoretic mobility, and kinetics).

     2. Creatine Kinase (CK):

        • Isoenzymes: CK-MM (muscle), CK-BB (brain), CK-MB (heart).

        • Diagnostic Importance: The level of CK-MB is a highly specific marker for diagnosing Myocardial Infarction (Heart Attack). It rises within 4-6 hours, peaks at 12-24 hours, and returns to normal in 2-3 days.

     3. Lactate Dehydrogenase (LDH):

        • Isoenzymes: LDH1 to LDH5. LDH1 and LDH2 are predominant in the heart.

        • Diagnostic Importance: A "flipped ratio" (LDH1 > LDH2) is also indicative of a myocardial infarction, though it is less specific than CK-MB and Troponins.

4. Diagnostic Significance of Serum Enzymes

   • Years: Aug 2015

   • Question: Discuss the diagnostic significance of serum enzymes.

   • Key:

     1. Introduction: Explain that intracellular enzymes are normally present at low levels in the plasma. Tissue damage or disease causes these enzymes to leak into the bloodstream, and their elevated levels can be used as diagnostic markers.

     2. Cardiac Markers: CK-MB and LDH1 for Myocardial Infarction.

     3. Liver Markers:

        • ALT and AST for hepatocellular damage (e.g., hepatitis).

        • ALP and GGT for cholestasis (bile duct obstruction).

     4. Pancreatic Marker: Amylase and Lipase for acute pancreatitis.

     5. Bone Marker: Alkaline Phosphatase (ALP) for bone disorders like rickets and Paget's disease.

5. Secondary Structure of Proteins (α-helix)

   • Years: Mar 2012

   • Question: Define secondary structure of proteins and mention its types. Describe the α-helix.

   • Key:

     1. Definition: Define secondary structure as the local, regular, folded arrangement of the polypeptide backbone, stabilized by hydrogen bonds.

     2. Types: The two major types are the α-helix and the β-pleated sheet.

     3. α-helix Description:

        • Structure: A right-handed, coiled or spiral conformation.

        • Stabilization: Stabilized by intramolecular hydrogen bonds between the C=O group of one amino acid and the N-H group of the amino acid four residues ahead in the chain.

        • Characteristics: Each turn contains 3.6 amino acid residues. The R-groups (side chains) project outwards from the helix.

        • Disruptors: Proline (the "helix breaker") and electrostatic repulsion between charged R-groups can disrupt the helix.

6. Transamination

   • Years: Jul 2017, Aug 2019

   • Question: Define transamination and explain by giving two examples.

   • Key:

     1. Definition: The transfer of an amino group (-NH₂) from an amino acid to a keto acid, thereby forming a new amino acid and a new keto acid.

     2. Coenzyme: This reaction is catalyzed by transaminases (or aminotransferases) and requires Pyridoxal Phosphate (PLP) (from Vitamin B6) as a coenzyme.

     3. Significance: It is a key reaction for the synthesis of non-essential amino acids and for funneling amino groups towards urea synthesis.

     4. Examples (with equations):

        • Alanine + α-ketoglutarate ⇌ Pyruvate + Glutamate (Catalyzed by ALT)

        • Aspartate + α-ketoglutarate ⇌ Oxaloacetate + Glutamate (Catalyzed by AST)

7. Digestion & Absorption of Proteins

   • Years: Feb 2017

   • Question: Explain the digestion and absorption of proteins.

   • Key:

     1. Stomach:

        • HCI: Denatures proteins and activates pepsinogen.

        • Pepsin: An endopeptidase that hydrolyzes proteins into smaller polypeptides.

     2. Small Intestine (Pancreatic Enzymes):

        • Trypsin & Chymotrypsin: Endopeptidases that break down polypeptides.

        • Carboxypeptidases: Exopeptidases that remove amino acids from the C-terminus.

     3. Small Intestine (Intestinal Enzymes):

        • Aminopeptidases & Dipeptidases: Located on the brush border, they complete the digestion into free amino acids, dipeptides, and tripeptides.

     4. Absorption: Free amino acids are absorbed via Na⁺-dependent secondary active transport. Di- and tripeptides are absorbed via a separate H⁺-cotransporter (PepT1) and are then hydrolyzed to amino acids inside the enterocyte.

II. Carbohydrate & Lipid Metabolism

1. TCA Cycle

   • Years: Aug 2014

   • Question: Describe the Tricarboxylic Acid Cycle.

   • Key:

     1. Definition & Location: The final common oxidative pathway for carbohydrates, fats, and amino acids. Occurs in the mitochondrial matrix.

     2. Reactions: Draw the cycle, starting from the condensation of Acetyl-CoA and Oxaloacetate to form Citrate. Label all 8 intermediates and the key enzymes.

     3. Energy Yield: State the products per cycle: 3 NADH, 1 FADH₂, 1 GTP (or ATP), which equals 10 ATP via oxidative phosphorylation.

     4. Regulation: Mention the three key regulatory enzymes: Citrate Synthase, Isocitrate Dehydrogenase, and α-Ketoglutarate Dehydrogenase. Note their activators (ADP, Ca²⁺) and inhibitors (ATP, NADH).

2. Gluconeogenesis

   • Years: Aug 2015, Nov 2020

   • Question: Describe gluconeogenesis.

   • Key:

     1. Definition & Site: The synthesis of new glucose from non-carbohydrate precursors (like lactate, glycerol, glucogenic amino acids). Occurs primarily in the liver.

     2. Bypass Reactions: Explain that it is not a simple reversal of glycolysis. Describe the four key bypass enzymes that circumvent the three irreversible steps of glycolysis:

        • Pyruvate Carboxylase & PEPCK (bypass Pyruvate Kinase).

        • Fructose-1,6-bisphosphatase (bypasses PFK-1).

        • Glucose-6-phosphatase (bypasses Glucokinase/Hexokinase).

     3. 
        

     4. Regulation: Explain that it is hormonally regulated. Glucagon and Cortisol stimulate it, while Insulin inhibits it.

     5. Significance: Crucial for maintaining blood glucose levels during fasting or starvation.

3. Glycogen Metabolism

   • Years: Aug 2013, Jan 2018

   • Question: Describe glycogen metabolism / regulation of glycogen metabolism.

   • Key:

     1. Introduction: Define glycogen as the storage form of glucose in animals, primarily in the liver and muscle.

     2. Glycogenesis (Synthesis):

        • Key Enzyme: Glycogen Synthase.

        • Steps: Glucose → G6P → G1P → UDP-Glucose → Glycogen.

     3. Glycogenolysis (Breakdown):

        • Key Enzyme: Glycogen Phosphorylase.

        • Steps: Glycogen → Glucose-1-Phosphate. Also mention the debranching enzyme.

     4. Reciprocal Regulation: Explain that the two pathways are reciprocally regulated by hormones.

        • Insulin (in fed state): Activates Glycogen Synthase and inhibits Glycogen Phosphorylase.

        • Glucagon (in liver) / Epinephrine (in muscle): Activate Glycogen Phosphorylase and inhibit Glycogen Synthase via a cAMP-dependent cascade.

4. Glycogen Storage Diseases (GSDs)

   • Years: Aug 2019

   • Question: Describe glycogen storage diseases.

   • Key:

     1. Definition: A group of inherited metabolic disorders caused by a defect in an enzyme required for either glycogen synthesis or degradation. This leads to the accumulation of abnormal quantity or quality of glycogen in tissues.

     2. Von Gierke's Disease (Type I):

        • Deficient Enzyme: Glucose-6-phosphatase.

        • Features: Affects the liver. Severe fasting hypoglycemia, hepatomegaly, lactic acidosis.

     3. Pompe's Disease (Type II):

        • Deficient Enzyme: Lysosomal α-1,4-glucosidase.

        • Features: A lysosomal storage disease leading to cardiomegaly and muscle weakness.

     4. McArdle's Disease (Type V):

        • Deficient Enzyme: Muscle Glycogen Phosphorylase.

        • Features: Affects muscle. Exercise intolerance, painful muscle cramps, and myoglobinuria.

5. Ketogenesis & Regulation

   • Years: Mar 2012, Feb 2014, Nov 2020

   • Question: Describe the process of ketogenesis, its regulation, and the conditions that lead to ketoacidosis.

   • Key:

     1. Definition: The synthesis of ketone bodies (acetoacetate, 3-hydroxybutyrate, and acetone) from acetyl-CoA.

     2. Site: Occurs in the liver mitochondria.

     3. Pathway: Describe the steps: 2 Acetyl-CoA → Acetoacetyl-CoA → HMG-CoA → Acetoacetate. Acetoacetate can then be reduced to 3-hydroxybutyrate or decarboxylated to acetone.

     4. Regulation: Regulated by the availability of acetyl-CoA and the activity of the rate-limiting enzyme HMG-CoA synthase. It is stimulated during periods of high fatty acid oxidation (fasting, uncontrolled diabetes).

     5. Ketoacidosis: Occurs in conditions like uncontrolled Type 1 Diabetes and prolonged starvation, where overproduction of acidic ketone bodies overwhelms the blood's buffering capacity, leading to a drop in pH.

6. Fatty Acid Synthase (FAS) Complex

   • Years: Aug 2012

   • Question: Describe the fatty acid synthase complex.

   • Key:

     1. Definition: A large, multienzyme protein complex found in the cytosol that catalyzes the synthesis of fatty acids.

     2. Structure: It is a dimer of two identical polypeptide chains. Each monomer has seven different enzyme activities and an Acyl Carrier Protein (ACP) domain.

     3. Key Domains: Mention the two key thiol (-SH) groups: one on the ACP and one on a cysteine residue of the condensing enzyme.

     4. Process: The growing fatty acid chain is shuttled between these two -SH groups as it is elongated two carbons at a time, using acetyl-CoA as the primer and malonyl-CoA for elongation. The final product is typically palmitate (16:0).

7. Beta-Oxidation of Fatty Acids

   • Years: Aug 2018

   • Question: Explain the steps of beta-oxidation of fatty acids.

   • Key:

     1. Definition & Location: The major pathway for fatty acid breakdown, where fatty acids are sequentially cleaved into two-carbon units of acetyl-CoA. Occurs in the mitochondrial matrix.

     2. Activation & Transport: Fatty acids are first activated to Fatty Acyl-CoA in the cytosol. They are then transported into the mitochondria via the carnitine shuttle.

     3. Four Recurring Steps: Describe the four steps of the β-oxidation spiral:

        • Oxidation by FAD (produces FADH₂).

        • Hydration (adds water).

        • Oxidation by NAD⁺ (produces NADH).

        • Thiolysis (cleavage by Coenzyme A to release acetyl-CoA and a shortened fatty acyl-CoA).

     4. End Products: The process repeats until the fatty acid is completely converted to acetyl-CoA molecules, which then enter the TCA cycle.

8. Essential Fatty Acids

   • Years: Feb 2013, Aug 2015

   • Question: What are essential fatty acids? Enumerate them, list two functions, and one deficiency manifestation.

   • Key:

     1. Definition: Polyunsaturated fatty acids that cannot be synthesized by the human body because we lack the enzymes to introduce double bonds beyond carbon-9. They must be obtained from the diet.

     2. Enumeration:

        • Linoleic Acid (Omega-6 family).

        • α-Linolenic Acid (Omega-3 family).

     3. 
        

     4. Functions:

        • They are essential components of cell membranes, maintaining membrane fluidity.

        • They serve as precursors for the synthesis of eicosanoids like prostaglandins, thromboxanes, and leukotrienes.

     5. 
        

     6. Deficiency Manifestation: Deficiency is rare but can lead to scaly dermatitis (phrynoderma or toad skin) and poor wound healing.

9. Lipoproteins & Cholesterol Transport

   • Years: Feb 2015

   • Question: Describe the role of lipoproteins in cholesterol transport.

   • Key:

     1. Introduction: Define lipoproteins as complexes of lipids and proteins (apolipoproteins) that transport insoluble lipids like cholesterol and triglycerides in the blood.

     2. Exogenous Pathway (Dietary Fat): Chylomicrons transport dietary lipids from the intestine to peripheral tissues.

     3. Endogenous Pathway (Forward Transport):

        • VLDL (Very Low-Density Lipoprotein): Transports endogenously synthesized triglycerides and cholesterol from the liver to peripheral tissues.

        • LDL (Low-Density Lipoprotein): Formed from VLDL, it is the primary carrier of cholesterol to peripheral tissues. High LDL is a risk factor for atherosclerosis ("bad cholesterol").

     4. 
        

     5. Reverse Cholesterol Transport:

        • HDL (High-Density Lipoprotein): Transports excess cholesterol from peripheral tissues back to the liver for excretion. This is a protective mechanism ("good cholesterol").

10. Digestion & Absorption of Lipids/Carbohydrates

    • Years: Aug 2013, Feb 2013

    • Question: Explain the digestion and absorption of lipids/carbohydrates.

    • Key (for Lipids):

      1. Mouth & Stomach: Limited digestion by lingual and gastric lipases.

      2. Small Intestine (Major Site):

         • Emulsification: Bile salts from the liver break down large fat globules into smaller micelles.

         • Enzymatic Digestion: Pancreatic lipase hydrolyzes triglycerides into free fatty acids and 2-monoacylglycerol.

      3. 
         

      4. Absorption: The products (fatty acids, monoacylglycerols) are absorbed by the intestinal cells (enterocytes).

      5. Re-synthesis & Packaging: Inside the enterocyte, they are re-esterified back into triglycerides and packaged with apolipoproteins to form chylomicrons, which are then secreted into the lymph.

    • Key (for Carbohydrates):

      1. Mouth: Digestion begins with salivary α-amylase, which breaks down starch into smaller oligosaccharides.

      2. Stomach: Amylase is inactivated by stomach acid; no carbohydrate digestion occurs.

      3. Small Intestine:

         • Pancreatic α-amylase continues the breakdown of starch.

         • Disaccharidases (lactase, sucrase, maltase) located on the intestinal brush border break down disaccharides into monosaccharides (glucose, fructose, galactose).

      4. Absorption: Monosaccharides are absorbed into the enterocytes. Glucose and galactose are absorbed via SGLT1 (a Na⁺-dependent cotransporter). Fructose is absorbed via GLUT5 (facilitated diffusion). All are then transported into the bloodstream via GLUT2.

III. Nucleic Acids & Molecular Biology

1. Salvage Pathway of Purine Synthesis

   • Years: Aug 2012, Mar 2012

   • Question: Describe the salvage pathway of purine nucleotide synthesis with its significance and associated disorder.

   • Key:

     1. Definition: A pathway that recycles free purine bases (adenine, guanine, hypoxanthine) obtained from the diet or from the breakdown of nucleic acids.

     2. Reactions:

        • APRT (Adenine phosphoribosyltransferase): Adenine + PRPP → AMP.

        • HGPRT (Hypoxanthine-guanine phosphoribosyltransferase): Guanine + PRPP → GMP; Hypoxanthine + PRPP → IMP.

     3. Significance: It is an energy-saving pathway, consuming less ATP than the de novo synthesis pathway. It is particularly important in tissues that cannot perform de novo synthesis.

     4. Associated Disorder: A deficiency of HGPRT causes Lesch-Nyhan Syndrome, a severe genetic disorder characterized by hyperuricemia, gout, and neurological problems including self-mutilation.

2. Purine Catabolism & Associated Abnormalities

   • Years: Feb 2015

   • Question: How are purine nucleotides degraded? Add a note on abnormalities due to excessive purine catabolism.

   • Key:

     1. Pathway of Degradation:

        • Describe the steps where AMP and GMP are degraded. Both pathways converge at the formation of Xanthine.

        • Mention key enzymes like adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP).

        • Final Step: Xanthine oxidase catalyzes the oxidation of hypoxanthine to xanthine, and then xanthine to Uric Acid, the final end product in humans.

     2. Abnormalities:

        • Hyperuricemia & Gout: Caused by overproduction or underexcretion of uric acid, leading to the deposition of urate crystals in joints.

        • Lesch-Nyhan Syndrome: Caused by HGPRT deficiency, leading to increased de novo synthesis and massive overproduction of uric acid.

        • Adenosine Deaminase (ADA) Deficiency: Causes Severe Combined Immunodeficiency (SCID) due to the toxic buildup of deoxyadenosine in lymphocytes.

3. Formation of Uric Acid

   • Years: Aug 2015

   • Question: Describe uric acid formation and mention the clinical significance of its estimation.

   • Key:

     1. Source: Uric acid is the final breakdown product of purine metabolism in humans.

     2. Pathway: (Same pathway as Q.19). Emphasize the role of Xanthine Oxidase as the key enzyme that converts hypoxanthine to xanthine and then to uric acid.

     3. Clinical Significance of Estimation:

        • Measuring serum uric acid levels is crucial for diagnosing and monitoring Gout.

        • Elevated levels (hyperuricemia) can also be seen in conditions with high cell turnover (like cancer chemotherapy) and in renal disease.

4. Structure and Functions of tRNA

   • Years: Aug 2012

   • Question: Describe the structure and functions of tRNA.

   • Key:

     1. Function: Transfer RNA (tRNA) acts as an adaptor molecule in protein synthesis. It reads a specific codon on the mRNA and carries the corresponding amino acid to the ribosome.

     2. Structure:

        • It is a small RNA molecule (73-93 nucleotides).

        • Secondary Structure: It folds into a cloverleaf structure with four main arms:

          • Acceptor Arm: Has the CCA sequence at the 3' end where the amino acid attaches.

          • Anticodon Arm: Contains the three-base anticodon that base-pairs with the mRNA codon.

          • D Arm: Contains dihydrouracil.

          • TΨC Arm: Contains pseudouridine.

        • Tertiary Structure: The cloverleaf folds into a compact, inverted L-shape.

5. DNA Replication

   • Years: Feb 2014

   • Question: Describe the process of DNA replication.

   • Key:

     1. Definition: The process by which a parent DNA molecule is duplicated to produce two identical daughter DNA molecules. It is semiconservative.

     2. Initiation:

        • Begins at a specific site called the origin of replication.

        • Helicase unwinds the DNA double helix, creating a replication fork. Single-strand binding proteins (SSBs) stabilize the separated strands.

     3. Elongation:

        • Primase synthesizes a short RNA primer.

        • DNA Polymerase III synthesizes the new DNA strand in the 5' to 3' direction.

        • Leading Strand: Synthesized continuously.

        • Lagging Strand: Synthesized discontinuously in short fragments called Okazaki fragments.

     4. Termination:

        • DNA Polymerase I removes the RNA primers and replaces them with DNA.

        • DNA Ligase joins the Okazaki fragments by forming phosphodiester bonds.

6. Transcription in Prokaryotes

   • Years: Aug 2013

   • Question: Discuss the process of transcription in prokaryotes.

   • Key:

     1. Definition: The synthesis of an RNA molecule from a DNA template, catalyzed by RNA polymerase.

     2. Initiation:

        • The sigma (σ) factor of RNA polymerase recognizes and binds to the promoter region (containing -10 and -35 consensus sequences) on the DNA.

        • The DNA helix unwinds, and the sigma factor is released once transcription begins.

     3. Elongation:

        • The core RNA polymerase moves along the DNA template, synthesizing an RNA chain in the 5' to 3' direction using ribonucleoside triphosphates (ATP, GTP, CTP, UTP).

     4. Termination:

        • Rho-independent termination: A stable hairpin loop forms in the nascent RNA, followed by a string of U residues, which causes the RNA to dissociate from the DNA.

        • Rho-dependent termination: A protein called the Rho factor binds to the RNA and moves towards the RNA polymerase, causing it to detach.

7. Post-Transcriptional Modifications

   • Years: Aug 2019

   • Question: Describe post-transcriptional modifications with examples.

   • Key:

     1. Definition: The chemical modifications that a primary RNA transcript (pre-mRNA) undergoes in eukaryotes to become a mature, functional RNA molecule. These modifications occur in the nucleus.

     2. 5' Capping: The addition of a 7-methylguanosine cap to the 5' end of the pre-mRNA. This cap protects the mRNA from degradation and is important for ribosome binding during translation.

     3. 3' Polyadenylation: The addition of a poly-A tail (a string of 50-250 adenine nucleotides) to the 3' end. This tail increases the stability of the mRNA and aids in its export from the nucleus.

     4. Splicing: The removal of non-coding intervening sequences called introns and the joining of the coding sequences called exons. This process is carried out by a large complex called the spliceosome.

8. Genetic Code

   • Years: Feb 2016

   • Question: Describe the genetic code.

   • Key:

     1. Definition: The set of rules by which the nucleotide sequence of a gene is translated into the amino acid sequence of a protein.

     2. Triplet Nature: The code is read in groups of three nucleotides, called a codon. Each codon specifies a particular amino acid.

     3. Degeneracy: The code is degenerate, meaning that most amino acids are specified by more than one codon (e.g., Leucine has 6 codons).

     4. Non-overlapping and Commaless: The code is read continuously from a fixed starting point without any punctuation between codons.

     5. Universality: The code is nearly universal, meaning that the same codons specify the same amino acids in almost all organisms, from bacteria to humans.

IV. Heme, Vitamins & Minerals

1. Heme Degradation & Bilirubin Fate

   • Years: Sep 2011, Feb 2013, Aug 2013

   • Question: Outline the degradation of heme. Add a note on the fate of conjugated bilirubin in the intestine.

   • Key:

     1. Site: Occurs in the reticuloendothelial cells of the liver, spleen, and bone marrow.

     2. Pathway:

        • Heme Oxygenase: Heme is cleaved to form Biliverdin (a green pigment), releasing iron and carbon monoxide.

        • Biliverdin Reductase: Biliverdin is reduced to Bilirubin (a yellow-orange pigment).

     3. Transport: Unconjugated bilirubin is transported to the liver bound to albumin.

     4. Conjugation in Liver: In the liver, bilirubin is conjugated with glucuronic acid by the enzyme UDP-glucuronyltransferase to form water-soluble bilirubin diglucuronide (conjugated bilirubin).

     5. Fate in Intestine: Conjugated bilirubin is excreted into the intestine via bile. Intestinal bacteria convert it into urobilinogen. Most urobilinogen is oxidized to stercobilin (giving stool its brown color). A small amount is reabsorbed, enters the enterohepatic circulation, and is excreted in the urine as urobilin (giving urine its yellow color).

2. Iron Storage and Absorption

   • Years: Sep 2011, Feb 2013, Mar 2021

   • Question: Write briefly on the storage and absorption of iron from the intestine.

   • Key:

     1. Dietary Iron: Iron exists in two forms: Heme iron (from animal sources) and Non-heme iron (from plant sources).

     2. Absorption Site: Primarily in the duodenum and upper jejunum.

     3. Mechanism of Absorption:

        • Non-heme iron (Fe³⁺) is reduced to ferrous iron (Fe²⁺) by enzymes like duodenal cytochrome b.

        • Fe²⁺ is transported into the enterocyte by the Divalent Metal Transporter 1 (DMT1). Heme iron is absorbed via a separate heme carrier protein.

     4. Fate inside Enterocyte: Iron can either be stored within the enterocyte bound to ferritin or transported out into the bloodstream.

     5. Regulation & Transport: The transport of iron out of the enterocyte is regulated by the hormone hepcidin. Once in the blood, iron binds to the transport protein transferrin.

     6. Storage: Iron is stored primarily in the liver, spleen, and bone marrow as ferritin and hemosiderin.

3. Co-enzyme Role of Thiamine (Vitamin B1)

   • Years: Aug 2014

   • Question: Discuss the co-enzyme role of thiamine and its deficiency disorder.

   • Key:

     1. Active Form: The active coenzyme form of thiamine is Thiamine Pyrophosphate (TPP).

     2. Role in Carbohydrate Metabolism: TPP is a crucial coenzyme for key enzymes involved in energy generation from carbohydrates:

        • Pyruvate Dehydrogenase Complex: Converts pyruvate to acetyl-CoA.

        • α-Ketoglutarate Dehydrogenase Complex: A key enzyme in the TCA cycle.

     3. Role in HMP Shunt: TPP is a coenzyme for Transketolase, an enzyme in the non-oxidative phase of the HMP shunt.

     4. Deficiency Disorder: Deficiency of thiamine leads to Beri-Beri.

        • Dry Beri-Beri: Characterized by peripheral neuropathy and muscle weakness.

        • Wet Beri-Beri: Characterized by cardiovascular symptoms like high-output cardiac failure and edema.

        • Wernicke-Korsakoff Syndrome: Seen in alcoholics, with neurological symptoms like confusion, ataxia, and memory loss.

4. Biochemical Functions & Deficiency of Vitamin B12

   • Years: Feb 2015

   • Question: Describe the biochemical functions and deficiency manifestations of vitamin B12.

   • Key:

     1. Active Forms: Cobalamin's active coenzyme forms are Methylcobalamin and Deoxyadenosylcobalamin.

     2. Biochemical Functions (Two key reactions):

        • Homocysteine to Methionine: Methylcobalamin is a coenzyme for methionine synthase. This reaction is linked to folate metabolism (prevents the "folate trap").

        • Methylmalonyl-CoA to Succinyl-CoA: Deoxyadenosylcobalamin is a coenzyme for methylmalonyl-CoA mutase, an important step in the metabolism of odd-chain fatty acids and some amino acids.

     3. Deficiency Manifestations:

        • Megaloblastic Anemia: Due to the functional folate deficiency (folate trap), impairing DNA synthesis in rapidly dividing hematopoietic cells.

        • Neurological Symptoms: Due to the accumulation of methylmalonyl-CoA, which interferes with myelin sheath formation, leading to subacute combined degeneration of the spinal cord.

5. Calcium Homeostasis & Hormonal Regulation

   • Years: Aug 2015, Mar 2021

   • Question: Explain the hormonal regulation of serum calcium.

   • Key:

     1. Introduction: State the normal serum calcium level (9-11 mg/dL) and mention that it is tightly regulated by three main hormones.

     2. Parathyroid Hormone (PTH):

        • Stimulus: Secreted in response to low blood calcium.

        • Actions:

          • Increases calcium resorption from bone.

          • Increases calcium reabsorption in the kidney.

          • Stimulates the kidney to synthesize the active form of Vitamin D (Calcitriol).

        • Overall Effect: Increases blood calcium.

     3. Calcitriol (Active Vitamin D):

        • Stimulus: Its synthesis is stimulated by PTH.

        • Actions:

          • Its primary action is to increase the absorption of dietary calcium from the intestine.

        • Overall Effect: Increases blood calcium.

     4. Calcitonin:

        • Stimulus: Secreted by the thyroid gland in response to high blood calcium.

        • Actions:

          • Inhibits calcium resorption from bone.

          • Increases calcium excretion by the kidney.

        • Overall Effect: Decreases blood calcium (has a weaker role in humans compared to PTH).

V. Clinical & General Biochemistry

1. Protein Energy Malnutrition (PEM)

   • Years: Mar 2012

   • Question: Define protein energy malnutrition and compare marasmus and kwashiorkor.

   • Key:

     1. Definition: PEM is a range of pathological conditions arising from a coincident lack of dietary protein and/or energy (calories) in varying proportions.

     2. Comparison Table:

Feature Marasmus Kwashiorkor

Primary Deficiency Severe deficiency of Calories (Energy) Severe deficiency of Protein

Age Usually infants (< 1 year) Usually older children (1-3 years)

Appearance Severe muscle wasting, "skin and bones" look Edema (especially in feet, face), pot belly

Subcutaneous Fat Lost Preserved

Appetite Good Poor

Serum Albumin Near normal Markedly reduced (causes edema)

Hepatomegaly Absent Present (due to fatty liver)

1. Acid-Base Balance (Blood Buffers & Renal Mechanism)

   • Years: Feb 2014

   • Question: Explain briefly on blood buffers and add a note on the renal mechanism of maintaining acid-base balance.

   • Key:

     1. Introduction: The body maintains blood pH in a narrow range of 7.35-7.45. This is achieved by buffer systems, the respiratory system, and the renal system.

     2. Blood Buffers (First line of defense):

        • Bicarbonate Buffer System (H₂CO₃ / HCO₃⁻): The most important extracellular buffer.

        • Phosphate Buffer System: More important intracellularly.

        • Protein Buffer System: Hemoglobin is a very important buffer inside red blood cells.

     3. Renal Mechanism (Long-term regulation):

        • Excretion of H⁺: The kidneys excrete excess acid (H⁺ ions), primarily in the form of titratable acids (like H₂PO₄⁻) and ammonium ions (NH₄⁺).

        • Reabsorption of HCO₃⁻: The kidneys reabsorb virtually all the filtered bicarbonate to conserve the body's buffer capacity.

        • Generation of New HCO₃⁻: During acidosis, the kidneys can generate new bicarbonate ions to replenish the buffer system.

2. Metabolic Acidosis

   • Years: Jul 2017

   • Question: Describe metabolic acidosis.

   • Key:

     1. Definition: A primary acid-base disorder characterized by a decrease in plasma bicarbonate (HCO₃⁻) concentration, which leads to a decrease in blood pH (<7.35).

     2. Causes (based on Anion Gap):

        • High Anion Gap Metabolic Acidosis: Caused by the addition of fixed acids. (Mnemonic: MUDPILES - Methanol, Uremia, Diabetic Ketoacidosis, Paraldehyde, Isoniazid, Lactic acidosis, Ethylene glycol, Salicylates).

        • Normal Anion Gap Metabolic Acidosis: Caused by the loss of bicarbonate (e.g., severe diarrhea) or impaired renal acid excretion.

     3. 
        

     4. Compensation: The primary compensatory mechanism is respiratory. The low pH stimulates chemoreceptors, leading to hyperventilation (Kussmaul breathing) to blow off CO₂ and raise the pH back towards normal.

     5. Biochemical Findings: Low serum HCO₃⁻, low blood pH, and a compensatory low pCO₂.

3. Porphyrias

   • Years: Jul 2017, Jan 2018

   • Question: Describe porphyrias / porphyrias presenting with photosensitivity.

   • Key:

     1. Definition: A group of inherited (or sometimes acquired) disorders caused by a deficiency of a specific enzyme in the heme synthesis pathway.

     2. Pathophysiology: The enzyme defect leads to the accumulation of porphyrin precursors (like ALA and PBG) or porphyrins.

     3. Classification & Features:

        • Acute Porphyrias: Characterized by the accumulation of precursors ALA and PBG, leading to neuropsychiatric symptoms (abdominal pain, confusion). Example: Acute Intermittent Porphyria (AIP). These are generally not photosensitive.

        • Cutaneous Porphyrias (Photosensitive): Characterized by the accumulation of porphyrins, which are photosensitizers. When exposed to light, they generate reactive oxygen species that damage the skin. Example: Porphyria Cutanea Tarda (PCT) or Congenital Erythropoietic Porphyria (CEP), leading to blistering and fragile skin.

4. Clearance & Its Estimation

   • Years: Feb 2016

   • Question: Define clearance and how it is estimated. Add a note on its diagnostic importance.

   • Key:

     1. Definition: Renal clearance of a substance is the hypothetical volume of blood plasma from which that substance is completely removed by the kidneys per unit of time.

     2. Formula: Clearance (C) = (U × V) / P

        • U: Concentration of the substance in urine.

        • V: Rate of urine flow (volume per minute).

        • P: Concentration of the substance in plasma.

     3. 
        

     4. Estimation of GFR: To measure the Glomerular Filtration Rate (GFR), we use a substance that is freely filtered by the glomerulus but is neither reabsorbed nor secreted by the tubules.

        • Gold Standard: Inulin clearance gives the true GFR.

        • Clinical Practice: Creatinine clearance is commonly used as a practical estimate of GFR.

     5. 
        

     6. Diagnostic Importance: The GFR is the best overall indicator of kidney function. A reduced clearance value indicates impaired renal function.

5. Detoxification (Ammonia)

   • Years: Jan 2020

   • Question: Discuss the detoxification of ammonia in the body. Mention two inborn errors associated with it.

   • Key:

     1. Toxicity: Ammonia is highly toxic, especially to the central nervous system. The body must have efficient mechanisms to detoxify it.

     2. Major Pathway (Urea Cycle): The primary mechanism for ammonia detoxification is its conversion to non-toxic urea in the liver via the Urea Cycle.

     3. Minor Pathways:

        • Synthesis of non-essential amino acids like glutamate and glutamine. The formation of glutamine from glutamate (catalyzed by glutamine synthetase) is particularly important in the brain for trapping ammonia.

     4. 
        

     5. Inborn Errors (Urea Cycle Defects):

        • Ornithine Transcarbamylase (OTC) Deficiency: The most common urea cycle disorder. Leads to hyperammonemia and orotic aciduria.

        • Carbamoyl Phosphate Synthetase I (CPS I) Deficiency: A severe defect in the first step of the cycle.

VI. General Metabolism & Bioenergetics

1. Chemiosmotic Mechanism of ATP Synthesis

   • Years: Feb 2015

   • Question: Describe the chemiosmotic mechanism of ATP synthesis.

   • Key:

     1. Theory: Proposed by Peter Mitchell, it explains how the energy from the electron transport chain (ETC) is used to synthesize ATP.

     2. Proton Pumping: As electrons pass through the ETC complexes (I, III, and IV) in the inner mitochondrial membrane, energy is used to pump protons (H⁺) from the mitochondrial matrix into the intermembrane space.

     3. Proton Motive Force: This pumping action creates an electrochemical gradient across the inner mitochondrial membrane, consisting of both a pH gradient (chemical potential) and a voltage gradient (electrical potential). This gradient is called the proton-motive force.

     4. ATP Synthase: The protons flow back down their concentration gradient into the matrix through a specific channel in the ATP synthase (also known as Complex V) enzyme.

     5. ATP Synthesis: The energy released by this proton flow drives the conformational changes in the ATP synthase enzyme, catalyzing the synthesis of ATP from ADP and Pi.

2. Electron Transport Chain (ETC)

   • Years: Jul 2017

   • Question: Give a diagrammatic representation of the mitochondrial electron transport chain and location of ATP synthesis.

   • Key:

     1. Location: The components of the ETC are located in the inner mitochondrial membrane.

     2. Diagram: Draw a clear diagram of the inner mitochondrial membrane.

        • Label the five complexes (I, II, III, IV, and V).

        • Show the mobile carriers: Coenzyme Q (Ubiquinone) and Cytochrome c.

        • Illustrate the flow of electrons: from NADH (at Complex I) and FADH₂ (at Complex II) down the chain to Oxygen (the final electron acceptor at Complex IV), which is reduced to water.

     3. Proton Pumping: Indicate with arrows that Complexes I, III, and IV pump protons (H⁺) from the matrix to the intermembrane space.

     4. Location of ATP Synthesis: Clearly label Complex V (ATP Synthase) as the site where protons re-enter the matrix, driving the synthesis of ATP.

3. HMP Shunt Pathway & Its Importance

   • Years: Jan 2020

   • Question: Mention the major functions of the HMP shunt pathway. Explain its importance in erythrocytes.

   • Key:

     1. Definition: The Hexose Monophosphate (HMP) Shunt, or Pentose Phosphate Pathway, is an alternative pathway for glucose oxidation.

     2. Major Functions:

        • Production of NADPH: This is the primary function. NADPH is essential for reductive biosynthesis (e.g., fatty acid synthesis) and for antioxidant defense.

        • Production of Ribose-5-phosphate: This pentose sugar is a vital precursor for the synthesis of nucleotides and nucleic acids (DNA, RNA).

     3. Importance in Erythrocytes (RBCs):

        • RBCs lack mitochondria and rely entirely on the HMP shunt for their supply of NADPH.

        • Antioxidant Role: NADPH is crucial in RBCs for maintaining a high level of reduced glutathione (GSH) via the enzyme glutathione reductase.

        • Protection: GSH protects the red blood cell from oxidative damage by detoxifying reactive oxygen species. A deficiency of the HMP shunt enzyme G6PD leads to a lack of NADPH, causing oxidative stress and hemolytic anemia.

VII. Miscellaneous & Applied Topics

1. Copper Metabolism

   • Years: Aug 2018

   • Question: Explain briefly on absorption, transport, and functions of copper.

   • Key:

     1. Absorption: Copper is absorbed in the stomach and upper small intestine.

     2. Transport: In the portal blood, it is transported to the liver bound to albumin. The liver incorporates copper into ceruloplasmin, which is then secreted into the blood. Ceruloplasmin is the main copper-carrying protein in the plasma.

     3. Functions: Copper is an essential trace element that functions as a cofactor for several important enzymes (metalloenzymes):

        • Cytochrome c Oxidase: The terminal enzyme of the electron transport chain.

        • Superoxide Dismutase (SOD): An antioxidant enzyme.

        • Lysyl Oxidase: Essential for the cross-linking of collagen and elastin.

        • Tyrosinase: Involved in melanin synthesis.

     4. Excretion: Excess copper is excreted from the body via bile. This process is impaired in Wilson's disease.

2. DNA Repair Mechanisms

   • Years: Aug 2018

   • Question: Explain the DNA repair mechanisms.

   • Key:

     1. Introduction: Define DNA repair as a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome.

     2. Base Excision Repair (BER):

        • Function: Repairs damage to a single base (e.g., deamination, oxidation).

        • Mechanism: A DNA glycosylase removes the damaged base, and then an endonuclease, DNA polymerase, and ligase fill the gap.

     3. Nucleotide Excision Repair (NER):

        • Function: Repairs bulky, helix-distorting lesions, such as thymine dimers caused by UV light.

        • Mechanism: A segment of the damaged strand is excised and then resynthesized using the intact strand as a template. A defect in this pathway causes Xeroderma Pigmentosum.

     4. Mismatch Repair (MMR):

        • Function: Corrects mismatched bases that arise during DNA replication.

        • Mechanism: The system identifies the newly synthesized strand, removes the mismatched nucleotide, and replaces it. A defect causes Lynch syndrome (HNPCC).

3. Glucose Transporters (GLUTs)

   • Years: Feb 2016

   • Question: Describe glucose transporters.

   • Key:

     1. Definition: Glucose transporters are a family of membrane proteins that facilitate the transport of glucose across cell membranes. They primarily function via facilitated diffusion.

     2. GLUT1: Found in most tissues, including red blood cells and the brain. Responsible for basal glucose uptake.

     3. GLUT2: Found in the liver, pancreatic β-cells, and intestine. It is a high-capacity, low-affinity transporter, acting as a "glucose sensor" in the pancreas.

     4. GLUT3: The primary glucose transporter in neurons.

     5. GLUT4: The insulin-dependent glucose transporter, found in adipose tissue and skeletal muscle. In response to insulin, GLUT4 vesicles move to the cell surface to increase glucose uptake.

     6. SGLT1: A sodium-glucose cotransporter (not a GLUT) found in the intestine and kidney, responsible for secondary active transport of glucose.

4. Recombinant DNA Technology & Applications

   • Years: Jan 2020, Nov 2020

   • Question: Describe recombinant DNA technology and its applications.

   • Key:

     1. Definition: A set of techniques used to join together DNA segments from different sources and transfer the resulting recombinant DNA molecule into a host organism to produce new genetic combinations.

     2. Key Tools:

        • Restriction Enzymes: To cut DNA at specific sites.

        • DNA Ligase: To join DNA fragments.

        • Vectors: Plasmids or viruses used to carry the recombinant DNA into a host cell.

        • Host Organism: Typically bacteria (like E. coli) or yeast.

     3. Applications:

        • Production of Therapeutics: Mass production of human proteins like insulin, growth hormone, and interferons.

        • Vaccine Production: Development of subunit vaccines (e.g., Hepatitis B vaccine).

        • Diagnosis: Creation of DNA probes and PCR-based tests for diagnosing genetic and infectious diseases.

        • Gene Therapy: Correcting defective genes to treat genetic disorders.

5. Metabolism of Tryptophan

   • Years: Mar 2021

   • Question: Describe the metabolism of tryptophan.

   • Key:

     1. Introduction: Tryptophan is an essential, aromatic amino acid that is both glucogenic and ketogenic.

     2. Major Catabolic Pathway (Kynurenine Pathway):

        • The primary pathway for tryptophan breakdown.

        • Leads to the formation of Alanine (glucogenic) and Acetyl-CoA (ketogenic).

        • This pathway is also important because it can lead to the de novo synthesis of Niacin (Vitamin B3).

     3. Synthesis of Serotonin:

        • Tryptophan is hydroxylated and then decarboxylated to form the neurotransmitter Serotonin, which regulates mood and sleep.

     4. Synthesis of Melatonin:

        • In the pineal gland, serotonin is further converted into Melatonin, the hormone that regulates the sleep-wake cycle.

     5. Clinical Correlation: Hartnup's disease, a defect in neutral amino acid transport, can lead to tryptophan deficiency and pellagra-like symptoms.

6. Prostaglandins: Functional & Therapeutic Role

   • Years: Jan 2019

   • Question: What are the functional and therapeutic roles of prostaglandins?

   • Key:

     1. Definition: Prostaglandins are lipid compounds derived from the essential fatty acid arachidonic acid via the cyclooxygenase (COX) pathway. They act locally as hormone-like signaling molecules.

     2. Functional Roles:

        • Inflammation: They are potent mediators of inflammation, causing pain, fever, and vasodilation.

        • Stomach: They protect the stomach lining by increasing mucus secretion and decreasing acid production.

        • Blood Clotting: Thromboxane A₂ (a related eicosanoid) promotes platelet aggregation, while Prostacyclin (PGI₂) inhibits it.

        • Reproduction: They are involved in uterine contractions during labor.

     3. 
        

     4. Therapeutic Role:

        • NSAIDs (Non-steroidal anti-inflammatory drugs) like aspirin and ibuprofen work by inhibiting the COX enzymes, thereby blocking prostaglandin synthesis. This reduces pain and inflammation.

        • Synthetic prostaglandins are used to induce labor and to treat peptic ulcers.

7. Structure of DNA

   • Years: Jan 2019

   • Question: Describe the structure of DNA.

   • Key:

     1. Watson-Crick Model: DNA exists as a right-handed double helix.

     2. Components of a Strand: Each strand is a polymer of deoxyribonucleotides. Each nucleotide consists of a deoxyribose sugar, a phosphate group, and a nitrogenous base (Adenine, Guanine, Cytosine, or Thymine). The nucleotides are linked by phosphodiester bonds.

     3. Two Strands: The two polynucleotide strands are coiled around a central axis.

        • They are antiparallel, meaning they run in opposite directions (one is 5' to 3', the other is 3' to 5').

        • The sugar-phosphate backbones are on the outside of the helix, and the bases are on the inside.

     4. 
        

     5. Base Pairing: The strands are held together by hydrogen bonds between complementary bases: Adenine pairs with Thymine (2 H-bonds), and Guanine pairs with Cytosine (3 H-bonds). This is known as Chargaff's rule.

     6. Grooves: The helix has a major groove and a minor groove, which are important for the binding of regulatory proteins.

8. Catabolism of Purines

   • Years: Jan 2019

   • Question: Describe the catabolism of purines.

   • Key: (This is very similar to Q.19 but with a different focus)

     1. Introduction: Purine nucleotides (AMP, GMP) from the breakdown of nucleic acids are degraded to the final end product, Uric Acid, in humans.

     2. Pathway for AMP:

        • AMP is deaminated to IMP or converted to Adenosine.

        • Adenosine is deaminated by Adenosine Deaminase (ADA) to Inosine.

        • Inosine is converted to Hypoxanthine.

     3. Pathway for GMP:

        • GMP is converted to Guanosine.

        • Guanosine is converted to Guanine.

        • Guanine is deaminated to Xanthine

     4. Common Final Steps:

        • Xanthine Oxidase oxidizes Hypoxanthine to Xanthine.

        • Xanthine Oxidase then oxidizes Xanthine to Uric Acid.

     5. Clinical Correlation: A defect in ADA causes SCID. Inhibition of Xanthine Oxidase by allopurinol is the treatment for Gout.

9. Regulation of Blood Glucose Level

   • Years: Aug 2018

   • Question: Describe the regulation of blood glucose level.

   • Key:

     1. Introduction: The blood glucose level is tightly maintained within a narrow range (70-100 mg/dL in fasting state) by the coordinated action of several hormones.

     2. Hyperglycemic Hormones (Raise blood glucose):

        • Glucagon: The primary hormone of the fasting state. It stimulates hepatic glycogenolysis and gluconeogenesis.

        • Epinephrine (Adrenaline): Released during stress, it stimulates glycogenolysis in both the liver and muscle.

        • Cortisol & Growth Hormone: Have a slower, more prolonged effect, generally promoting gluconeogenesis and decreasing glucose uptake by peripheral tissues.

     3. Hypoglycemic Hormone (Lowers blood glucose):

        • Insulin: The primary hormone of the fed state. It is secreted by pancreatic β-cells in response to high blood glucose.

        • Actions of Insulin:

          • Increases glucose uptake into muscle and adipose tissue (via GLUT4).

          • Stimulates glycolysis and glycogen synthesis.

          • Inhibits glycogenolysis and gluconeogenesis.