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🧪 MBBS 1st Year Biochemistry - Viva Spots
A high-yield, exam-ready collection of key facts, mnemonics, and must-know points across all major topics.
1. CARBOHYDRATES & GLYCOLYSIS
Key Facts
- Glycolysis occurs in the cytoplasm (cytosol) of ALL cells
- Net ATP from glycolysis: 2 ATP (aerobic or anaerobic)
- Total ATP from 1 glucose (aerobic): 30-32 ATP
Rate-Limiting Enzyme (most asked!)
| Pathway | Rate-Limiting Enzyme |
|---|
| Glycolysis | Phosphofructokinase-1 (PFK-1) |
| TCA cycle | Isocitrate dehydrogenase |
| Gluconeogenesis | Fructose-1,6-bisphosphatase |
| Glycogen synthesis | Glycogen synthase |
| Glycogenolysis | Glycogen phosphorylase |
| Urea cycle | Carbamoyl phosphate synthetase I (CPS I) |
| Fatty acid synthesis | Acetyl CoA carboxylase |
| Beta-oxidation | Carnitine acyltransferase I |
| HMP shunt | Glucose-6-phosphate dehydrogenase (G6PD) |
| Cholesterol synthesis | HMG-CoA reductase |
Viva tip: "What activates PFK-1?" → AMP (low energy signal). "What inhibits PFK-1?" → ATP and citrate (high energy signals).
Irreversible Steps of Glycolysis (mnemonic: "PEP")
- P - hexokinase/glucokinase (Glucose → G6P)
- PFK-1 (F6P → F1,6BP) - the KEY regulated step
- P - pyruvate kinase (PEP → Pyruvate)
Gluconeogenesis bypass enzymes (reverse the irreversible steps):
- Pyruvate kinase → Pyruvate carboxylase + PEPCK
- PFK-1 → Fructose-1,6-bisphosphatase
- Hexokinase → Glucose-6-phosphatase (liver only - so liver can release free glucose)
2. TCA CYCLE (Krebs Cycle)
- Location: Mitochondrial matrix
- Per turn of cycle yields: 3 NADH, 1 FADH₂, 1 GTP, 2 CO₂
- Starting substrate: Acetyl CoA (2C) + OAA (4C) → Citrate (6C)
Key Enzymes
| Enzyme | Substrate → Product |
|---|
| Citrate synthase | OAA + Acetyl CoA → Citrate |
| Isocitrate dehydrogenase (rate-limiting) | Isocitrate → α-Ketoglutarate + CO₂ |
| α-Ketoglutarate dehydrogenase | α-KG → Succinyl CoA + CO₂ |
| Succinyl CoA synthetase | Succinyl CoA → Succinate (GTP formed) |
| Succinate dehydrogenase | Succinate → Fumarate (uses FAD) |
Mnemonic for TCA intermediates: "Clever Student In Study Generates Feelings Marvelously Or Accept" - Citrate, aconitase → Isocitrate, α-Ketoglutarate, Succinyl-CoA, Succinate, Fumarate, Malate, OAA
3. ENZYMES - HIGH YIELD VIVA SPOTS
Michaelis-Menten Kinetics
- Km = substrate concentration at which reaction velocity = ½ Vmax
- Low Km = HIGH affinity for substrate
- High Km = LOW affinity for substrate
Types of Inhibition
| Type | Km | Vmax | Lineweaver-Burk |
|---|
| Competitive | Increased | Unchanged | Same Y-intercept, different X-intercept |
| Non-competitive | Unchanged | Decreased | Same X-intercept, different Y-intercept |
| Uncompetitive | Decreased | Decreased | Parallel lines |
Classic competitive inhibitor example: Methotrexate inhibits dihydrofolate reductase (DHFR) - competes with folate
Irreversible Inhibitors
- Aspirin - irreversibly inhibits COX-1/COX-2 (acetylates serine)
- Organophosphates - irreversibly inhibit acetylcholinesterase
- Lead - inhibits ferrochelatase (heme synthesis) and ALA dehydratase
- Penicillin - suicide inhibitor of transpeptidase
Isoenzymes (exam favourite!)
| Enzyme | Clinical Use |
|---|
| LDH-1 (heart) | Elevated in MI (heart attacks) |
| LDH-5 (liver) | Elevated in liver disease |
| CK-MB | Most specific for MI |
| CK-MM | Skeletal muscle damage |
| Alkaline phosphatase (ALP) | Liver/bone disease, pregnancy |
| Gamma-GT (GGT) | Alcoholic liver disease |
4. PROTEINS & AMINO ACIDS
Protein Structure
| Level | Bonds/Interactions |
|---|
| Primary | Peptide bonds (covalent) |
| Secondary (α-helix, β-sheet) | Hydrogen bonds |
| Tertiary | Disulfide bonds, hydrophobic, ionic, H-bonds |
| Quaternary | Same as tertiary (between subunits) |
Essential Amino Acids (mnemonic: "PVT TIM HaLL")
Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Leucine, Lysine
- Conditionally essential: Arginine, Tyrosine, Cysteine, Glutamine, Proline
- Only purely ketogenic: Leucine and Lysine
Amino Acid Characteristics
- Only amino acid with imidazole ring: Histidine (acts as buffer at physiological pH)
- Only amino acid without chiral center: Glycine
- Only amino acid with disulfide bonds: Cysteine (→ Cystine when oxidized)
- Amino acid with indole ring: Tryptophan
- Amino acid precursor to serotonin: Tryptophan → 5-hydroxytryptamine
- Amino acid precursor to dopamine/epinephrine: Tyrosine
- Amino acid precursor to NO (nitric oxide): Arginine
5. UREA CYCLE
- Location: Liver (both mitochondria and cytosol)
- Purpose: Convert toxic ammonia (NH₃) to non-toxic urea
Steps & Enzymes
- CPS I (rate-limiting, mitochondria): NH₃ + CO₂ → Carbamoyl phosphate
- OTC (mitochondria): Carbamoyl phosphate + Ornithine → Citrulline
- ASS (cytosol): Citrulline + Aspartate → Argininosuccinate
- ASL (cytosol): Argininosuccinate → Arginine + Fumarate
- Arginase (cytosol): Arginine + H₂O → Urea + Ornithine
Key: CPS I is activated by N-acetylglutamate (NAG), which is synthesized from acetyl CoA + glutamate.
Hyperammonemia - Enzyme Defects
- Most common urea cycle disorder: OTC deficiency (X-linked)
- Presents with: Elevated ammonia, low urea, neurological symptoms
6. LIPIDS & LIPOPROTEINS
Fatty Acid Synthesis vs Beta-Oxidation
| Fatty Acid Synthesis | Beta-Oxidation |
|---|
| Location | Cytosol | Mitochondria |
| Carrier | Acyl carrier protein (ACP) | CoA |
| Coenzyme | NADPH | FAD + NAD⁺ |
| Regulation | Acetyl CoA carboxylase (rate-limiting) | Carnitine shuttle |
Cholesterol Synthesis
- Rate-limiting step: HMG-CoA → Mevalonate (by HMG-CoA reductase)
- Statins inhibit HMG-CoA reductase
- Synthesis occurs mainly in liver (cytosol/ER)
- Cholesterol is a precursor to: bile acids, steroid hormones, vitamin D
Lipoproteins (high yield!)
| Lipoprotein | Main Lipid | Function |
|---|
| Chylomicrons | Triglycerides (dietary) | Transport dietary fat from gut |
| VLDL | Triglycerides (endogenous) | Transport liver-made TG |
| IDL | TG + Cholesterol | Intermediate |
| LDL | Cholesterol | "Bad" - delivers cholesterol to tissues |
| HDL | Protein (highest) | "Good" - reverse cholesterol transport |
Mnemonic for lipoprotein density (highest → lowest): "Horrible Villain LDL" → HDL > LDL > IDL > VLDL > Chylomicron
Key Apolipoproteins
- Apo B-48: Chylomicrons
- Apo B-100: VLDL, IDL, LDL (LDL receptor ligand)
- Apo E: VLDL, IDL, HDL (receptor-mediated uptake)
- Apo C-II: Activates lipoprotein lipase (LPL)
- Apo A-I: HDL (activates LCAT)
7. VITAMINS - COMPLETE SPOT TABLE
Fat-Soluble Vitamins (A, D, E, K)
| Vitamin | Active Form | Function | Deficiency | Toxicity |
|---|
| A | Retinol, Retinoic acid | Vision (rhodopsin), epithelial integrity | Night blindness, Xerophthalmia, Keratomalacia | Teratogenic, liver damage |
| D | 1,25-dihydroxycholecalciferol (Calcitriol) | Ca²⁺ & phosphate absorption | Rickets (children), Osteomalacia (adults) | Hypercalcemia |
| E | α-tocopherol | Antioxidant (prevents lipid peroxidation) | Hemolytic anemia, spinocerebellar degeneration | Rare |
| K | Menaquinone/Phylloquinone | Cofactor for γ-carboxylation of clotting factors (II, VII, IX, X) | Bleeding, prolonged PT | Hemolysis in G6PD deficiency |
Water-Soluble Vitamins
| Vitamin | Coenzyme | Function | Deficiency |
|---|
| B1 (Thiamine) | TPP | Pyruvate dehydrogenase, α-KGD, Transketolase | Beriberi (wet=cardiac, dry=peripheral neuropathy), Wernicke-Korsakoff |
| B2 (Riboflavin) | FAD, FMN | Electron carrier (oxidation-reduction) | Cheilitis, glossitis, corneal vascularization |
| B3 (Niacin) | NAD⁺, NADP⁺ | Redox reactions (> 400 enzymes) | Pellagra (4 Ds: Dermatitis, Diarrhea, Dementia, Death) |
| B5 (Pantothenic acid) | CoA | Acyl transfer reactions | Burning feet syndrome (rare) |
| B6 (Pyridoxine) | PLP (pyridoxal phosphate) | Transamination, decarboxylation, heme synthesis | Peripheral neuropathy, convulsions (sideroblastic anemia) |
| B7 (Biotin) | Biotin | CO₂ fixation (carboxylations) | Dermatitis, alopecia (raw egg white = avidin blocks biotin) |
| B9 (Folate) | THF (tetrahydrofolate) | One-carbon transfers, purine synthesis, thymidylate synthesis | Megaloblastic anemia (NO neurological symptoms) |
| B12 (Cobalamin) | Methylcobalamin, Adenosylcobalamin | Methionine synthesis, fatty acid metabolism | Megaloblastic anemia + subacute combined degeneration of spinal cord |
| C (Ascorbic acid) | - | Collagen synthesis (hydroxylation of proline/lysine), antioxidant, iron absorption | Scurvy (bleeding gums, perifollicular hemorrhage, corkscrew hair) |
Key B12 vs Folate difference: Both cause megaloblastic anemia, but ONLY B12 deficiency causes neurological symptoms (subacute combined degeneration).
Viva Trap: Biotin deficiency is caused by consuming raw eggs (avidin in raw egg white binds biotin). Cooking denatures avidin.
8. HEMOGLOBIN
Types of Normal Hemoglobin
| Type | Chains | When Present |
|---|
| HbA | α₂β₂ | Adults (major, ~97%) |
| HbA₂ | α₂δ₂ | Adults (minor, ~2.5%) - increased in β-thalassemia |
| HbF | α₂γ₂ | Fetus/newborn (higher O₂ affinity) |
| HbA1c | Glycated HbA | Reflects 3-month blood glucose control |
Oxygen Dissociation Curve - Shifts
Right Shift = Decreased O₂ affinity = More O₂ delivery to tissues (CADET, face Right!)
- CO₂ increase
- Acid (low pH)
- DPG (2,3-DPG) increase
- Exercise
- Temperature increase
Left Shift = Increased O₂ affinity (HbF, CO poisoning, alkalosis, low 2,3-DPG)
Hemoglobinopathies
- Sickle cell disease: Glu → Val substitution at position 6 of β-chain (HbS)
- Autosomal recessive; crisis triggered by acidosis, dehydration, infection
- Sickle crisis confirmed by: Hb electrophoresis (HbSS)
- β-Thalassemia: Deficient β-chain synthesis → microcytic hypochromic anemia + increased HbA₂ & HbF
- HbA1c >6.5% = diagnostic of diabetes mellitus
9. DNA, RNA & MOLECULAR BIOLOGY
DNA Replication (Prokaryotes vs Eukaryotes)
| Feature | Prokaryotes | Eukaryotes |
|---|
| Origin of replication | Single | Multiple |
| Direction | Bidirectional | Bidirectional |
| DNA polymerase | DNA Pol III (main) | DNA Pol α, δ, ε |
| Proofreading | 3'→5' exonuclease | 3'→5' exonuclease |
Key Enzymes in Replication
- Helicase: Unwinds double helix
- Topoisomerase: Relieves tension ahead of replication fork (inhibited by fluoroquinolones)
- Primase: Lays RNA primer
- DNA polymerase: Synthesizes new strand (5'→3' direction only)
- DNA ligase: Joins Okazaki fragments
Transcription
- Template strand (antisense): read 3'→5'
- mRNA product: synthesized 5'→3'
- RNA Pol I: rRNA; RNA Pol II: mRNA (pre-mRNA); RNA Pol III: tRNA, 5S rRNA
- α-amanitin (Amanita mushroom toxin) inhibits RNA Pol II
Translation
- Start codon: AUG (codes for Methionine)
- Stop codons: UAA, UAG, UGA ("U Are Away, U Are Gone, U Go Away")
- Ribosomes: 80S (eukaryotes) = 60S + 40S; 70S (prokaryotes) = 50S + 30S
- Prokaryotic 30S inhibitors: Aminoglycosides, Tetracyclines
- Prokaryotic 50S inhibitors: Macrolides, Chloramphenicol, Clindamycin
10. INBORN ERRORS OF METABOLISM
| Disease | Deficient Enzyme | Accumulates | Findings |
|---|
| Phenylketonuria (PKU) | Phenylalanine hydroxylase (PAH) | Phenylalanine | Musty/mousy odor, intellectual disability, fair skin/hair; Rx: low Phe diet + tyrosine |
| Alkaptonuria | Homogentisate oxidase | Homogentisic acid | Dark urine on standing, ochronosis (dark pigment in cartilage), arthritis |
| Albinism | Tyrosinase | No melanin | Lack of pigment, photosensitivity (NOT associated with neurological issues) |
| Maple Syrup Urine Disease | Branched-chain α-keto acid dehydrogenase | Leucine, Isoleucine, Valine | Maple syrup smell in urine, neurological damage; Rx: restrict branched-chain AAs |
| Homocystinuria | Cystathionine β-synthase (most common) | Homocysteine | Marfanoid body habitus, lens subluxation (downward & inward), thrombosis |
| Galactosemia | Galactose-1-phosphate uridyltransferase | Galactose-1-P | Jaundice, cataracts, intellectual disability; Rx: galactose-free diet |
| G6PD deficiency | G6PD | Low glutathione | Hemolytic anemia precipitated by oxidant stress (drugs, infection, fava beans) |
| Gaucher disease | Glucocerebrosidase | Glucocerebroside | Hepatosplenomegaly, Gaucher cells (crumpled tissue paper appearance) |
| Tay-Sachs | Hexosaminidase A | GM2 ganglioside | Cherry-red spot on macula, progressive neurodegeneration; no hepatosplenomegaly |
| Niemann-Pick | Sphingomyelinase | Sphingomyelin | Cherry-red spot + hepatosplenomegaly, "foamy" macrophages |
11. QUICK-FIRE VIVA SPOTS
- Glucokinase vs Hexokinase: Glucokinase is in liver only, high Km, not saturated at normal glucose → behaves as glucose sensor; not inhibited by G6P
- Cori cycle: Lactate from muscle → liver → glucose (via gluconeogenesis) → back to muscle
- Glucose-alanine cycle: Muscle alanine → liver → urea + glucose
- Respiratory quotient (RQ): Carbohydrates = 1.0; Fat = 0.7; Protein = 0.8
- Only fuel for RBCs: Glucose (no mitochondria, no fatty acid oxidation)
- Only fuel for brain during starvation: Ketone bodies (mainly β-hydroxybutyrate)
- 2,3-DPG is high in: Stored blood, anemia, high altitude (right shifts curve - more O₂ release)
- Hormone that activates glycogen phosphorylase: Glucagon (in liver), Epinephrine (liver + muscle)
- Hormone that activates glycogen synthase: Insulin
- Acetyl CoA cannot be converted to glucose (pyruvate dehydrogenase reaction is irreversible)
- Carbon source for fatty acid synthesis: Acetyl CoA (transported out of mitochondria as citrate)
- Substrate-level phosphorylation: Occurs in glycolysis (step 7 & 10) and TCA (succinyl CoA → succinate)
- Oxidative phosphorylation: Occurs in inner mitochondrial membrane via ATP synthase (Complex V)
12. CLINICAL BIOCHEMISTRY SPOTS
| Lab Test | Normal Value | Clinical Significance |
|---|
| Blood glucose (fasting) | 70-100 mg/dL | >126 mg/dL = diabetes (x2) |
| HbA1c | <5.7% | 5.7-6.4% = prediabetes; ≥6.5% = diabetes |
| Total cholesterol | <200 mg/dL | >240 = high risk |
| LDL | <100 mg/dL | Primary target in dyslipidemia |
| Serum albumin | 3.5-5.5 g/dL | Low in malnutrition, liver disease, nephrotic syndrome |
| Uric acid | 3.5-7.2 mg/dL | Elevated in gout (purine metabolism disorder) |
| Serum urea (BUN) | 7-20 mg/dL | Elevated in renal failure, high protein diet |
| Serum creatinine | 0.6-1.2 mg/dL | Marker of GFR (renal function) |
MASTER MNEMONICS SUMMARY
| Mnemonic | For |
|---|
| "PVT TIM HaLL" | Essential amino acids |
| "CADET face Right" | Right shift of O₂ dissociation curve |
| "UAA, UAG, UGA" | Stop codons |
| "Fat-soluble ADEK" | Fat-soluble vitamins (stored in body, can cause toxicity) |
| "Pellagra = 4 Ds" | Dermatitis, Diarrhea, Dementia, Death |
| "Beriberi = B1" | Thiamine deficiency |
| "Scurvy = no Collagen" | Vitamin C - hydroxylates Pro/Lys in collagen |
| "B12 = Brain + Blood" | Neurological + megaloblastic anemia |
| "Folate = just Blood" | Only megaloblastic anemia, NO neuro |
Sources: Lippincott's Illustrated Reviews: Biochemistry 8e; Harper's Illustrated Biochemistry 32e; Basic Medical Biochemistry: A Clinical Approach 6e; Harrison's Principles of Internal Medicine 22e; Robbins & Kumar Basic Pathology