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MBBS 1st year biochemistry viva spots important topics key facts

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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!)

PathwayRate-Limiting Enzyme
GlycolysisPhosphofructokinase-1 (PFK-1)
TCA cycleIsocitrate dehydrogenase
GluconeogenesisFructose-1,6-bisphosphatase
Glycogen synthesisGlycogen synthase
GlycogenolysisGlycogen phosphorylase
Urea cycleCarbamoyl phosphate synthetase I (CPS I)
Fatty acid synthesisAcetyl CoA carboxylase
Beta-oxidationCarnitine acyltransferase I
HMP shuntGlucose-6-phosphate dehydrogenase (G6PD)
Cholesterol synthesisHMG-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")

  1. P - hexokinase/glucokinase (Glucose → G6P)
  2. PFK-1 (F6P → F1,6BP) - the KEY regulated step
  3. 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

EnzymeSubstrate → Product
Citrate synthaseOAA + Acetyl CoA → Citrate
Isocitrate dehydrogenase (rate-limiting)Isocitrate → α-Ketoglutarate + CO₂
α-Ketoglutarate dehydrogenaseα-KG → Succinyl CoA + CO₂
Succinyl CoA synthetaseSuccinyl CoA → Succinate (GTP formed)
Succinate dehydrogenaseSuccinate → 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

TypeKmVmaxLineweaver-Burk
CompetitiveIncreasedUnchangedSame Y-intercept, different X-intercept
Non-competitiveUnchangedDecreasedSame X-intercept, different Y-intercept
UncompetitiveDecreasedDecreasedParallel 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!)

EnzymeClinical Use
LDH-1 (heart)Elevated in MI (heart attacks)
LDH-5 (liver)Elevated in liver disease
CK-MBMost specific for MI
CK-MMSkeletal muscle damage
Alkaline phosphatase (ALP)Liver/bone disease, pregnancy
Gamma-GT (GGT)Alcoholic liver disease

4. PROTEINS & AMINO ACIDS

Protein Structure

LevelBonds/Interactions
PrimaryPeptide bonds (covalent)
Secondary (α-helix, β-sheet)Hydrogen bonds
TertiaryDisulfide bonds, hydrophobic, ionic, H-bonds
QuaternarySame 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

  1. CPS I (rate-limiting, mitochondria): NH₃ + CO₂ → Carbamoyl phosphate
  2. OTC (mitochondria): Carbamoyl phosphate + Ornithine → Citrulline
  3. ASS (cytosol): Citrulline + Aspartate → Argininosuccinate
  4. ASL (cytosol): Argininosuccinate → Arginine + Fumarate
  5. 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 SynthesisBeta-Oxidation
LocationCytosolMitochondria
CarrierAcyl carrier protein (ACP)CoA
CoenzymeNADPHFAD + NAD⁺
RegulationAcetyl 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!)

LipoproteinMain LipidFunction
ChylomicronsTriglycerides (dietary)Transport dietary fat from gut
VLDLTriglycerides (endogenous)Transport liver-made TG
IDLTG + CholesterolIntermediate
LDLCholesterol"Bad" - delivers cholesterol to tissues
HDLProtein (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)

VitaminActive FormFunctionDeficiencyToxicity
ARetinol, Retinoic acidVision (rhodopsin), epithelial integrityNight blindness, Xerophthalmia, KeratomalaciaTeratogenic, liver damage
D1,25-dihydroxycholecalciferol (Calcitriol)Ca²⁺ & phosphate absorptionRickets (children), Osteomalacia (adults)Hypercalcemia
Eα-tocopherolAntioxidant (prevents lipid peroxidation)Hemolytic anemia, spinocerebellar degenerationRare
KMenaquinone/PhylloquinoneCofactor for γ-carboxylation of clotting factors (II, VII, IX, X)Bleeding, prolonged PTHemolysis in G6PD deficiency

Water-Soluble Vitamins

VitaminCoenzymeFunctionDeficiency
B1 (Thiamine)TPPPyruvate dehydrogenase, α-KGD, TransketolaseBeriberi (wet=cardiac, dry=peripheral neuropathy), Wernicke-Korsakoff
B2 (Riboflavin)FAD, FMNElectron 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)CoAAcyl transfer reactionsBurning feet syndrome (rare)
B6 (Pyridoxine)PLP (pyridoxal phosphate)Transamination, decarboxylation, heme synthesisPeripheral neuropathy, convulsions (sideroblastic anemia)
B7 (Biotin)BiotinCO₂ fixation (carboxylations)Dermatitis, alopecia (raw egg white = avidin blocks biotin)
B9 (Folate)THF (tetrahydrofolate)One-carbon transfers, purine synthesis, thymidylate synthesisMegaloblastic anemia (NO neurological symptoms)
B12 (Cobalamin)Methylcobalamin, AdenosylcobalaminMethionine synthesis, fatty acid metabolismMegaloblastic anemia + subacute combined degeneration of spinal cord
C (Ascorbic acid)-Collagen synthesis (hydroxylation of proline/lysine), antioxidant, iron absorptionScurvy (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

TypeChainsWhen Present
HbAα₂β₂Adults (major, ~97%)
HbA₂α₂δ₂Adults (minor, ~2.5%) - increased in β-thalassemia
HbFα₂γ₂Fetus/newborn (higher O₂ affinity)
HbA1cGlycated HbAReflects 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)

FeatureProkaryotesEukaryotes
Origin of replicationSingleMultiple
DirectionBidirectionalBidirectional
DNA polymeraseDNA Pol III (main)DNA Pol α, δ, ε
Proofreading3'→5' exonuclease3'→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

DiseaseDeficient EnzymeAccumulatesFindings
Phenylketonuria (PKU)Phenylalanine hydroxylase (PAH)PhenylalanineMusty/mousy odor, intellectual disability, fair skin/hair; Rx: low Phe diet + tyrosine
AlkaptonuriaHomogentisate oxidaseHomogentisic acidDark urine on standing, ochronosis (dark pigment in cartilage), arthritis
AlbinismTyrosinaseNo melaninLack of pigment, photosensitivity (NOT associated with neurological issues)
Maple Syrup Urine DiseaseBranched-chain α-keto acid dehydrogenaseLeucine, Isoleucine, ValineMaple syrup smell in urine, neurological damage; Rx: restrict branched-chain AAs
HomocystinuriaCystathionine β-synthase (most common)HomocysteineMarfanoid body habitus, lens subluxation (downward & inward), thrombosis
GalactosemiaGalactose-1-phosphate uridyltransferaseGalactose-1-PJaundice, cataracts, intellectual disability; Rx: galactose-free diet
G6PD deficiencyG6PDLow glutathioneHemolytic anemia precipitated by oxidant stress (drugs, infection, fava beans)
Gaucher diseaseGlucocerebrosidaseGlucocerebrosideHepatosplenomegaly, Gaucher cells (crumpled tissue paper appearance)
Tay-SachsHexosaminidase AGM2 gangliosideCherry-red spot on macula, progressive neurodegeneration; no hepatosplenomegaly
Niemann-PickSphingomyelinaseSphingomyelinCherry-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 TestNormal ValueClinical 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/dLPrimary target in dyslipidemia
Serum albumin3.5-5.5 g/dLLow in malnutrition, liver disease, nephrotic syndrome
Uric acid3.5-7.2 mg/dLElevated in gout (purine metabolism disorder)
Serum urea (BUN)7-20 mg/dLElevated in renal failure, high protein diet
Serum creatinine0.6-1.2 mg/dLMarker of GFR (renal function)

MASTER MNEMONICS SUMMARY

MnemonicFor
"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
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