🔥 1st MBBS Biochem Viva - EMERGENCY CHEAT SHEET

Read the bolded lines. Say those words confidently. That's your marks.

VIVA I TOPICS

1. CELL

• Basic structural & functional unit of life
• Cell organelles: Nucleus (DNA storage), Mitochondria ("powerhouse" - ATP via oxidative phosphorylation), ER (rough = ribosomes + protein synthesis; smooth = lipid synthesis), Golgi (packaging + secretion), Lysosomes ("suicide bags" - contain hydrolytic enzymes)
• Plasma membrane: Fluid mosaic model (Singer & Nicolson) - lipid bilayer with embedded proteins
• Cell cycle: G1 → S (DNA replication) → G2 → M (mitosis)

2. PROTEIN CHEMISTRY & METABOLISM

• Amino acids: 20 standard; 9 essential (cannot be synthesized - must be in diet): His, Ile, Leu, Lys, Met, Phe, Thr, Trp, Val (mnemonic: "HiL MiPTTV")
• Protein structure levels:
  • Primary = amino acid sequence (peptide bonds)
  • Secondary = α-helix or β-sheet (H-bonds)
  • Tertiary = 3D folding (disulfide bonds, hydrophobic interactions)
  • Quaternary = multiple subunits (e.g., hemoglobin = 2α + 2β)
• Protein denaturation: Loss of 3D structure without breaking peptide bonds
• Metabolism: Proteins degraded → amino acids → transamination/deamination → urea cycle (liver) → urea excreted in urine
• Nitrogen balance: Positive (growing child, pregnancy), Negative (starvation, burns, fever)

3. ENZYMES

• Definition: Biological catalysts - proteins (except ribozymes which are RNA)
• Active site: Where substrate binds; fits like a "lock and key" (Fischer) or induced fit (Koshland) model
• Km: Substrate concentration at half maximal velocity (Vmax/2) - measure of enzyme-substrate affinity. Low Km = high affinity
• Enzyme inhibition:
  • Competitive: Inhibitor resembles substrate; Km increases, Vmax unchanged. Example: Methotrexate inhibits DHFR
  • Non-competitive: Inhibitor binds allosteric site; Km unchanged, Vmax decreases
  • Irreversible: Inhibitor binds covalently. Example: Aspirin irreversibly inhibits COX
• Coenzymes vs Cofactors: Cofactors = inorganic (Mg2+, Zn2+); Coenzymes = organic (NAD+, FAD, CoA - derived from vitamins)
• Isoenzymes (Isozymes): Same reaction, different forms. LDH-1 (heart), LDH-5 (liver) - diagnostic importance
• 6 IUB classes: Oxidoreductases, Transferases, Hydrolases, Lyases, Isomerases, Ligases

4. VITAMINS

• Vitamin B12 absorption: Requires intrinsic factor (from gastric parietal cells). Deficiency → pernicious anemia

5. PURINES & PYRIMIDINES

• Purines: Adenine (A), Guanine (G) - double ring structure
• Pyrimidines: Cytosine (C), Thymine (T), Uracil (U) - single ring structure
• DNA: A=T, G≡C | RNA: A=U, G≡C
• De novo synthesis: Purines built on ribose-5-phosphate backbone (PRPP is key precursor). Pyrimidines ring built first, then attached to ribose
• Salvage pathway: Reuses free bases - important in brain and RBCs
• Purine catabolism → Uric acid (end product in humans) → Gout (hyperuricemia, MSU crystal deposition in joints)
• Allopurinol treats gout by inhibiting xanthine oxidase (the enzyme that makes uric acid)
• Pyrimidine catabolism → β-alanine (NOT uric acid)

6. NUCLEIC ACIDS

• DNA: Double helix (Watson & Crick, 1953) - antiparallel strands, right-handed B-form; sugar = deoxyribose
• RNA: Single stranded; sugar = ribose; Uracil instead of Thymine
• Types of RNA: mRNA (carries genetic code), tRNA (carries amino acids - anticodon), rRNA (structural component of ribosomes)
• Replication: Semiconservative (Meselson-Stahl); DNA polymerase reads 3'→5', synthesizes 5'→3'; needs RNA primer
• Transcription: DNA → RNA (RNA polymerase)
• Translation: mRNA → Protein (ribosomes); codons are triplets; AUG = start codon, UAA/UAG/UGA = stop codons
• Central Dogma: DNA → RNA → Protein

7. HEMOGLOBIN

• Structure: Globular protein, 4 subunits (2α + 2β in adult HbA), each with a heme group (porphyrin ring + Fe2+)
• Fe2+ carries oxygen (if oxidized to Fe3+ → methemoglobin, cannot carry O2)
• Oxygen dissociation curve: Sigmoid shape (cooperative binding - due to quaternary structure)
• Right shift (↑ O2 release to tissues): ↑ CO2, ↑ H+, ↑ temperature, ↑ 2,3-BPG = Bohr effect
• Left shift (↑ O2 affinity): ↓CO2, ↓H+, fetal Hb (HbF), CO poisoning
• HbF has γ-chains instead of β-chains; higher O2 affinity than HbA
• Abnormal Hb:
  • HbS (sickle cell) - Glu→Val at β6; HbC - Glu→Lys at β6
  • Thalassemia - quantitative defect (reduced chain synthesis)
• Myoglobin: Monomeric, hyperbolic O2 curve, stores O2 in muscle

8. BIOLOGICAL OXIDATION

• ETC (Electron Transport Chain): Inner mitochondrial membrane; 4 complexes (I, II, III, IV) + ATP synthase (Complex V)
• Complex I: NADH → CoQ (pumps 4H+)
• Complex II: FADH2 → CoQ (does NOT pump H+)
• Complex IV: Cytochrome c oxidase - final electron acceptor is O2 → H2O
• ATP yield: NADH = 2.5 ATP; FADH2 = 1.5 ATP; Complete glucose oxidation ≈ 30-32 ATP
• Chemiosmosis: H+ gradient drives ATP synthase (Mitchell's hypothesis)
• Uncouplers: DNP, thermogenin (brown fat) - dissipate proton gradient as heat without making ATP
• P:O ratio: Number of ATP made per oxygen atom consumed

9. GENETIC ENGINEERING

• Recombinant DNA technology: Cutting DNA (restriction endonucleases) + pasting into vectors (plasmids) + expressing in host cells
• Restriction enzymes: Cut DNA at specific palindromic sequences; produce "sticky ends"
• Vectors: Plasmids, bacteriophages, cosmids, BAC/YAC
• PCR (Polymerase Chain Reaction): Amplifies specific DNA sequences. Steps: Denaturation (94°C) → Annealing (50-65°C) → Extension (72°C). Uses Taq polymerase
• Gel electrophoresis: Separates DNA by size (smaller = migrates further)
• Southern blot: DNA; Northern blot: RNA; Western blot: Protein
• Gene therapy: Replacing defective genes (e.g., SCID, cystic fibrosis)
• CRISPR-Cas9: Modern precise gene editing tool

10. FREE RADICALS & ANTIOXIDANTS

• Free radical: Molecule with unpaired electron; highly reactive
• ROS (Reactive Oxygen Species): Superoxide (O2•-), Hydrogen peroxide (H2O2), Hydroxyl radical (•OH) - most dangerous
• Sources: Mitochondrial ETC, phagocytosis (respiratory burst), radiation, smoking
• Damage: Lipid peroxidation, DNA damage, protein oxidation → cell injury, aging, atherosclerosis, cancer
• Enzymatic antioxidants:
  • SOD (Superoxide dismutase): O2•- → H2O2
  • Catalase: H2O2 → H2O + O2
  • Glutathione peroxidase: H2O2 + GSH → H2O (requires selenium)
• Non-enzymatic antioxidants: Vitamin C, Vitamin E (most important lipid antioxidant), β-carotene, glutathione, uric acid

11. IMMUNE SYSTEM

• Innate: Non-specific; first line: skin, mucus, fever; cells: neutrophils, macrophages, NK cells; NO memory
• Adaptive: Specific; B cells (humoral - antibodies) + T cells (cell-mediated)
• Immunoglobulins (Antibodies): IgG (most abundant, crosses placenta), IgA (secretions - breast milk, saliva), IgM (first responder, pentamer), IgE (allergies, parasites), IgD (B cell surface receptor)
• MHC (HLA): MHC I - on all nucleated cells, presents to CD8+ cytotoxic T cells; MHC II - on APCs (macrophages, B cells, dendritic cells), presents to CD4+ helper T cells
• Complement system: C3b (opsonization), C5b-9 (MAC - membrane attack complex = cell lysis)
• Cytokines: IL-1 & TNF-α (fever, acute phase response); IL-2 (T cell proliferation); IFN-γ (activates macrophages)

12. NUTRITION

• Caloric values: Carbohydrates = 4 kcal/g, Proteins = 4 kcal/g, Fats = 9 kcal/g, Alcohol = 7 kcal/g
• BMR (Basal Metabolic Rate): Energy at rest; ~1800 kcal/day (male adult)
• Protein requirements: 0.8 g/kg/day adults; higher in growth, pregnancy, illness
• Malnutrition:
  • Marasmus: Calorie + protein deficiency; wasting, no edema
  • Kwashiorkor: Protein deficiency with adequate calories; edema, fatty liver, hypoalbuminemia
• Essential fatty acids: Linoleic acid (ω-6) and α-Linolenic acid (ω-3) - cannot be synthesized
• Dietary fiber: Not digested; reduces constipation, lowers LDL, reduces colon cancer risk

13. EXTRACELLULAR MATRIX (Collagen, Elastin)

• ECM components: Collagen, elastin, proteoglycans, fibronectin, laminin
• Collagen: Most abundant protein in human body (25-30% of total protein); triple helix (Gly-X-Y repeat; X=Pro, Y=Hydroxyproline); 28 types
  • Type I: Bone, skin, tendon (most abundant)
  • Type II: Cartilage
  • Type III: Blood vessels, skin (reticulin)
  • Type IV: Basement membrane
• Collagen synthesis: Fibroblasts → preprocollagen → procollagen (triple helix) → tropocollagen → collagen fibers. Needs Vitamin C for hydroxylation of Pro & Lys (deficiency → Scurvy)
• Elastin: Rubber-like; rich in Gly, Pro, Val; cross-linked by desmosine (unique); provides recoil (lung, arteries, skin)
• Marfan syndrome: FBN1 mutation (fibrillin-1) → defective microfibril scaffolding for elastin; tall stature, aortic aneurysm
• Ehlers-Danlos syndrome: Collagen synthesis/processing defects → hyperelastic skin, hypermobile joints

VIVA II TOPICS

1. CARBOHYDRATES

• Monosaccharides: Glucose, fructose, galactose (C6H12O6)
• Disaccharides: Sucrose = Glu+Fru; Lactose = Glu+Gal; Maltose = Glu+Glu
• Glycolysis: Glucose → 2 Pyruvate; in cytoplasm; net 2 ATP (anaerobic)
• TCA (Krebs) cycle: Acetyl-CoA → 3 NADH + 1 FADH2 + 1 GTP per turn; in mitochondria
• Key regulatory enzymes: Hexokinase/Glucokinase, PFK-1 (rate-limiting of glycolysis), Pyruvate kinase
• Glycogen metabolism: Glycogen synthase (synthesis); Glycogen phosphorylase (breakdown). Liver = maintains blood glucose; Muscle = fuel for itself
• Gluconeogenesis: Synthesis of glucose from non-glucose precursors (lactate, amino acids, glycerol) - mainly in liver, bypasses 3 irreversible steps of glycolysis
• HMP Shunt (Pentose Phosphate Pathway): Produces NADPH (antioxidant defense, fatty acid synthesis) + ribose-5-phosphate (nucleotide synthesis). G6PD deficiency → hemolytic anemia with oxidant drugs

2. LIPIDS

• Fatty acid oxidation (β-oxidation): Occurs in mitochondria; each cycle removes 2C as Acetyl-CoA + 1 NADH + 1 FADH2; palmitate (16C) → 8 Acetyl-CoA = 106 ATP net
• Ketone bodies: Acetoacetate, β-hydroxybutyrate, acetone; synthesized in liver (starvation, DM); used by brain during starvation
• Fatty acid synthesis: Cytoplasm; acetyl-CoA → malonyl-CoA (ACC enzyme, rate-limiting); NADPH needed
• Cholesterol: Synthesized from Acetyl-CoA; HMG-CoA reductase is rate-limiting enzyme (inhibited by statins)
• Lipoproteins:
  • Chylomicrons: Transport dietary fat from gut
  • VLDL: Transport endogenous triglycerides from liver
  • LDL: "Bad" cholesterol, delivers cholesterol to tissues
  • HDL: "Good" cholesterol, reverse cholesterol transport
• Atherosclerosis: LDL oxidation → foam cells → plaque

3. MINERAL METABOLISM

• Calcium: 99% in bone; regulated by PTH (↑Ca), Calcitonin (↓Ca), Vitamin D (↑Ca absorption); Hypocalcemia → Tetany (Chvostek sign, Trousseau sign)
• Phosphorus: Bone mineral, ATP, nucleic acids; inversely related to Ca in blood
• Iron: Absorbed as Fe2+ in duodenum; transported by transferrin; stored as ferritin/hemosiderin; deficiency → microcytic hypochromic anemia
• Zinc: Cofactor for >300 enzymes; deficiency → poor wound healing, hypogonadism, anosmia
• Iodine: Required for thyroid hormone synthesis; deficiency → goiter, cretinism

4. FUNCTION TESTS (KFT, LFT, TFT, AdFT)

• Serum creatinine (N: 0.6-1.2 mg/dL), BUN (N: 7-20 mg/dL), BUN:Creatinine ratio
• GFR (glomerular filtration rate) - best overall indicator of kidney function
• Urinalysis: protein, glucose, casts

• Bilirubin: Direct (conjugated) + Indirect (unconjugated); Total N <1.0 mg/dL
• Enzymes: AST, ALT (hepatocellular damage); ALP, GGT (cholestasis)
• Synthetic function: Serum albumin, PT/INR (clotting factors)

• TSH (most sensitive - elevated in hypothyroidism, low in hyperthyroidism)
• T3, T4 (free)
• Hypothyroid: ↑TSH, ↓T3/T4; Hyperthyroid: ↓TSH, ↑T3/T4

• Cortisol (serum morning), ACTH
• Dexamethasone suppression test: Cushing's syndrome screening
• Urine 17-ketosteroids, VMA (pheochromocytoma)

5. INVESTIGATION TECHNIQUES

• Spectrophotometry: Measures light absorbance to quantify substances
• Chromatography: Separates mixtures (paper, TLC, HPLC, column)
• Electrophoresis: Separates by charge/size (serum proteins, Hb variants)
• ELISA: Antigen-antibody reaction + enzyme-linked color change; used for HIV diagnosis, hormone assays
• Immunofluorescence: Antibody labeled with fluorescent dye
• PCR: DNA amplification
• Centrifugation: Separates by density (e.g., serum from blood)

6. WATER & ELECTROLYTE BALANCE

• ICF: ~60% of body water; main cation K+
• ECF: ~40% of body water; main cation Na+
• Dehydration types: Isotonic, Hypertonic, Hypotonic
• ADH (Vasopressin): Increases water reabsorption in collecting duct; released by hypothalamus in response to ↑osmolality
• Aldosterone: Increases Na+ reabsorption + K+ excretion in distal tubule
• SIADH: Excess ADH → dilutional hyponatremia, concentrated urine despite low serum osmolality

7. ACID-BASE BALANCE

• Normal pH: 7.35-7.45 (arterial blood)
• Buffers: Bicarbonate/H2CO3 (most important in blood), Phosphate, Proteins, Hemoglobin
• Henderson-Hasselbalch: pH = pKa + log [HCO3-] / [H2CO3] (= 6.1 + log 20/1 = 7.4)
• 4 Disorders:

  Disorder	pH	Primary change	Compensation
  Metabolic acidosis	↓	↓HCO3-	↑Ventilation (↓pCO2)
  Metabolic alkalosis	↑	↑HCO3-	↓Ventilation (↑pCO2)
  Respiratory acidosis	↓	↑pCO2	Kidneys retain HCO3-
  Respiratory alkalosis	↑	↓pCO2	Kidneys excrete HCO3-

8. DETOXIFICATION

• Main organ: Liver
• Phase I reactions: Oxidation, reduction, hydrolysis - often via Cytochrome P450 enzymes; make drugs more polar (may make some more reactive/toxic)
• Phase II reactions: Conjugation (glucuronidation, sulfation, acetylation, methylation) - makes compounds water soluble for excretion
• Ammonia detoxification: Urea cycle (liver) - NH3 → urea → excreted in urine; liver failure → hepatic encephalopathy
• Conjugation of bilirubin: Indirect bilirubin + glucuronic acid → direct bilirubin → excreted in bile

9. MODE OF HORMONE ACTION

• Receptor location based on hormone type:
  • Lipid-soluble hormones (steroids, thyroid): Intracellular receptors → act on DNA directly → gene expression changes (slow, long-lasting)
  • Water-soluble hormones (peptides, catecholamines): Cell surface receptors → second messengers (fast effects)
• Second messengers:
  • cAMP: Epinephrine, glucagon, TSH, PTH, LH/FSH (adenylyl cyclase - Gs protein)
  • IP3/DAG: Oxytocin, TRH, GNRH, α1 agonists (phospholipase C - Gq protein)
  • cGMP: ANP, nitric oxide
  • Ca2+: Also a second messenger (calmodulin pathway)

10. CANCER

• Oncogenes: Normal proto-oncogenes become oncogenes (accelerator stuck - promotes uncontrolled growth)
• Tumor suppressor genes: Brake genes; loss causes cancer. p53 ("guardian of the genome") most important - mutated in >50% of cancers; Rb (retinoblastoma)
• Key oncogenes: ras (most commonly mutated), myc, Her2/neu (breast cancer), BCR-ABL (CML - target of imatinib)
• Carcinogenesis steps: Initiation (DNA mutation) → Promotion → Progression
• Warburg effect: Cancer cells prefer aerobic glycolysis (lactic acid fermentation even in presence of O2)
• Tumor markers: AFP (hepatocellular ca, teratoma), CEA (colon), PSA (prostate), CA-125 (ovarian), β-hCG (choriocarcinoma)

11. STARVATION & INTEGRATION OF METABOLISM

• Well-fed state: Glucose → glycogen (liver/muscle) + triglycerides (adipose). Insulin dominant
• Fasting/Starvation phases:
  • Early fasting (hours): Glycogenolysis (liver glycogen depleted in ~24h)
  • Short-term starvation: Gluconeogenesis (from amino acids, lactate, glycerol); fat mobilization begins
  • Prolonged starvation: Ketone bodies become primary brain fuel; protein sparing; cortisol + glucagon dominant
• Metabolic interrelationships:
  • Liver: Central hub - glycolysis, gluconeogenesis, ketogenesis, urea cycle
  • Muscle: Uses glucose + fatty acids; produces alanine (alanine cycle) + lactate (Cori cycle)
  • Brain: Uses glucose normally; shifts to ketones in starvation
  • Adipose: Stores/releases fatty acids
• Cori cycle: Lactate (muscle) → liver → glucose → back to muscle

⚡ LAST-MINUTE GOLDEN RULES FOR THE VIVA

1. If asked anything about enzymes - mention Km, Vmax, competitive vs non-competitive inhibition
2. If asked about any vitamin - name the deficiency disease immediately
3. If asked about hemoglobin - mention cooperative binding, Bohr effect, 2,3-BPG
4. If asked about DNA - say "double helix, antiparallel, semiconservative replication, Watson & Crick 1953"
5. If asked about gout - link purines → uric acid → allopurinol → xanthine oxidase
6. For any metabolism - mention insulin (fed state) vs glucagon (fasting)
7. Stay calm - if you don't know, say "The key concept here is..." and relate it to something you do know

🧬 VITAMINS - FULL DETAIL (Viva Special)

THE BIG PICTURE FIRST (Say this if asked "classify vitamins")

"Vitamins are organic micronutrients required in small amounts for normal metabolic functions that the body cannot synthesize in adequate quantities. They are classified as fat-soluble (A, D, E, K) and water-soluble (B-complex and C). Fat-soluble vitamins are absorbed with dietary fat via lymphatics, stored in liver/adipose tissue, and can cause toxicity in excess. Water-soluble vitamins are not stored (except B12), excreted in urine, and act mainly as coenzymes."

FAT-SOLUBLE VITAMINS

🟡 VITAMIN A (Retinol)

1. Vision: Retinal + opsin → Rhodopsin (rod cells, night vision). Light bleaches rhodopsin → nerve impulse. Deficiency → night blindness (nyctalopia) = first sign
2. Epithelial integrity: Maintains differentiation of epithelial cells; deficiency → keratinization of epithelium
3. Immune function: Required for T-cell activation and antibody response
4. Reproduction: Spermatogenesis, fetal development
5. Gene expression: Retinoic acid binds nuclear receptors (RAR) → controls gene transcription

• Night blindness (earliest)
• Xerophthalmia (dry eye) → Bitot's spots (foamy, triangular white spots on conjunctiva)
• Keratomalacia (corneal ulceration/melting) → Blindness (late)
• Follicular hyperkeratosis (rough, dry skin - "toad skin")
• Increased infection susceptibility

🟡 VITAMIN D (Calciferol)

"Kidney is the organ that activates Vitamin D. PTH stimulates 1α-hydroxylase in the kidney."

1. Stimulates intestinal Ca2+ and phosphate absorption (via calbindin protein synthesis)
2. Promotes bone mineralization
3. Stimulates Ca2+ reabsorption in kidneys
4. Acts like a steroid hormone - binds VDR (Vitamin D Receptor) → nuclear receptor → gene transcription

• Children → Rickets: Soft bones, bow legs, knock knees, rachitic rosary (beaded costochondral junctions), craniotabes, Harrison's sulcus, delayed dentition
• Adults → Osteomalacia: Bone pain, fractures, muscle weakness, Looser zones on X-ray
• Elderly/Homebound: Most vulnerable (less sun + less skin synthesis)

🟡 VITAMIN E (Tocopherol)

• Most important lipid-soluble antioxidant - protects cell membranes (polyunsaturated fatty acids) from free radical damage (lipid peroxidation)
• Maintains RBC membrane integrity in newborns

• Hemolytic anemia in newborns
• Spinocerebellar ataxia, peripheral neuropathy (in adults with prolonged deficiency)
• Retinopathy

🟡 VITAMIN K (Phylloquinone / Menaquinone)

• Cofactor for γ-carboxylase enzyme → carboxylates glutamate residues on clotting factors II (Prothrombin), VII, IX, X → essential for their activation
• Also activates Protein C & Protein S (anticoagulants) and osteocalcin (bone)

• Bleeding tendency - Prolonged PT (Prothrombin Time) first sign
• Hemorrhagic disease of newborn (gut bacteria not yet colonized + no placental transfer)
• Fat malabsorption states (obstructive jaundice, celiac, Crohn's)

WATER-SOLUBLE VITAMINS (B-Complex + C)

🔵 VITAMIN B1 (Thiamine)

1. Pyruvate dehydrogenase (Pyruvate → Acetyl-CoA)
2. α-Ketoglutarate dehydrogenase (Krebs cycle)
3. Transketolase (HMP shunt / Pentose phosphate pathway)
4. Branched-chain keto-acid dehydrogenase

Key: TPP is essential for carbohydrate metabolism. Deficiency blocks energy production, especially affecting high-glucose-demanding tissues: brain and heart.

• Dry beriberi: Peripheral neuropathy (glove-stocking distribution), muscle weakness
• Wet beriberi: Dilated cardiomyopathy, edema, high-output cardiac failure
• Wernicke-Korsakoff syndrome (alcoholics): Wernicke's = confusion + ophthalmoplegia + ataxia (triad); Korsakoff's = anterograde amnesia + confabulation
• Infantile beriberi: Cardiac failure in breastfed infants of thiamine-deficient mothers

🔵 VITAMIN B2 (Riboflavin)

• Angular stomatitis (cracks at corners of mouth)
• Cheilosis (lip inflammation)
• Glossitis (magenta/purple tongue)
• Seborrheic dermatitis
• Corneal vascularization
• Normochromic normocytic anemia

🔵 VITAMIN B3 (Niacin / Nicotinic acid)

• NAD+ - predominantly in catabolism (accepts H in glycolysis, TCA cycle, β-oxidation)
• NADP+ - predominantly in anabolism (fatty acid synthesis, HMP shunt)

• 4 Ds: Dermatitis (photosensitive, symmetrical, "Casal's necklace"), Diarrhea, Dementia, Death
• Also in Hartnup disease (tryptophan absorption defect) and Carcinoid syndrome (tryptophan diverted to serotonin)

🔵 VITAMIN B5 (Pantothenic acid)

🔵 VITAMIN B6 (Pyridoxine)

1. Transamination (amino acid metabolism - aminotransferases)
2. Decarboxylation of amino acids → neurotransmitter synthesis: DOPA → Dopamine, 5-HTP → Serotonin, Glutamate → GABA, Histidine → Histamine
3. Heme synthesis (ALA synthase - rate-limiting enzyme needs PLP)
4. Glycogen phosphorylase (glycogenolysis)
5. Tryptophan → Niacin conversion

• Sideroblastic anemia (↓heme synthesis → iron accumulates in mitochondria of developing RBCs = ring sideroblasts)
• Peripheral neuropathy (↓neurotransmitters)
• Glossitis, seborrheic dermatitis
• Convulsions in infants (↓GABA)
• Antagonized by isoniazid (INH) - TB drug - so give B6 supplementation with INH

🔵 VITAMIN B7 (Biotin)

1. Pyruvate carboxylase (Pyruvate → Oxaloacetate - gluconeogenesis)
2. Acetyl-CoA carboxylase (Acetyl-CoA → Malonyl-CoA - fatty acid synthesis, rate-limiting)
3. Propionyl-CoA carboxylase

• Alopecia (hair loss), dermatitis, glossitis, CNS symptoms

🔵 VITAMIN B9 (Folic Acid / Folate)

1. DNA synthesis - carries 1C units needed for purine and thymidylate (dTMP) synthesis
2. Amino acid metabolism - Homocysteine → Methionine (with B12)
3. Cell division - rapidly dividing cells most affected

• Megaloblastic anemia (large, immature RBCs - macro-ovalocytes, hypersegmented neutrophils)
• Neural tube defects (spina bifida, anencephaly) - deficiency in early pregnancy
• No neurological symptoms (unlike B12 deficiency - key distinction!)
• Glossitis, diarrhea

🔵 VITAMIN B12 (Cobalamin)

1. Methylcobalamin: Cofactor for Methionine synthase - converts Homocysteine → Methionine using 5-methyl-THF (folate trap mechanism)
2. Adenosylcobalamin: Cofactor for Methylmalonyl-CoA mutase → Methylmalonyl-CoA → Succinyl-CoA (odd-chain FA metabolism, important in myelin)

• Pernicious anemia (autoimmune destruction of parietal cells or anti-IF antibodies)
• Strict vegans
• Gastrectomy, ileal disease (Crohn's), terminal ileum resection
• Fish tapeworm (Diphyllobothrium latum)

• Megaloblastic anemia (same as folate deficiency)
• Subacute Combined Degeneration of Spinal Cord (SACD): Demyelination of posterior columns (vibration/position sense loss) + lateral corticospinal tracts (upper motor neuron signs) - NOT seen in folate deficiency
• Glossitis (beefy red tongue)
• Peripheral neuropathy
• Raised Homocysteine AND raised Methylmalonic acid (MMA) in blood - MMA helps distinguish B12 from folate deficiency (in folate def, MMA is normal)

KEY EXAM POINT: Giving folic acid to a B12-deficient patient can correct the anemia but worsen the neurological damage ("masking" effect). This is why B12 must be ruled out before giving folate.

🔵 VITAMIN C (Ascorbic acid)

1. Collagen synthesis: Hydroxylation of Proline and Lysine residues in procollagen → needed for triple helix stability. Deficiency → defective collagen → scurvy
2. Antioxidant: Scavenges free radicals; regenerates Vitamin E
3. Iron absorption: Reduces Fe3+ → Fe2+ in gut (ferrous form is absorbed)
4. Immune function: Required for neutrophil function
5. Carnitine synthesis: Required for fatty acid transport into mitochondria
6. Norepinephrine synthesis: Dopamine β-hydroxylase requires Vit C
7. Bile acid synthesis: Cholesterol → bile acids (hydroxylation)

• Perifollicular hemorrhage (bleeding around hair follicles) - classic
• Bleeding gums (gingivitis), loosening of teeth
• Corkscrew hairs (swan-neck deformity of hair follicles)
• Poor wound healing
• Hemarthrosis (bleeding into joints)
• "Woody leg" (subperiosteal hemorrhage) in children
• Scorbutic rosary (in children - different from rachitic rosary of Vit D)
• Anemia (due to bleeding + impaired iron absorption + impaired folate metabolism)

🎯 THE VIVA GOLD TABLE - Common Coenzyme Connections

⚡ LIKELY VIVA QUESTIONS & ANSWERS