Important viva questions an examiner may ask on vitamins anlog with the answers (biochemistry)

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Important Viva Questions on Vitamins - Biochemistry

(Based on Harper's Illustrated Biochemistry, 32nd Ed. and Basic Medical Biochemistry, 6th Ed.)

Part 1: General / Foundational Questions

Q1. Define a vitamin. A vitamin is an organic nutrient required in small amounts for a variety of biochemical functions that, generally, cannot be synthesized by the body (or not in sufficient amounts) and must therefore be supplied in the diet. They are distinct from energy-providing macronutrients.

Q2. How are vitamins classified? Vitamins are classified into two broad groups:

Fat-soluble vitamins: A, D, E, K - absorbed with dietary fat; stored in the liver and adipose tissue; toxicity possible with excess intake (A and D)
Water-soluble vitamins: B-complex (B1, B2, B3, B5, B6, B7, B9, B12) and vitamin C - function mainly as enzyme cofactors; not stored in large amounts; excess generally excreted in urine

Q3. What is the difference between a vitamin, a provitamin, and an antivitamin?

Vitamin: the biologically active form
Provitamin (precursor): an inactive precursor converted to the active vitamin in the body (e.g., beta-carotene → vitamin A; 7-dehydrocholesterol → vitamin D3)
Antivitamin: a compound that antagonizes the action of a vitamin (e.g., avidin antagonizes biotin; dicoumarol antagonizes vitamin K)

Part 2: Fat-Soluble Vitamins

Vitamin A (Retinol)

Q4. What are the active forms of vitamin A and their functions?

Retinol: alcohol form; required for reproduction and cell differentiation
Retinal (retinaldehyde): aldehyde form; essential for vision - it is the prosthetic group of rhodopsin in rod cells
Retinoic acid: acid form; acts like a steroid hormone, binding nuclear receptors (RAR/RXR) to regulate gene expression; involved in cell differentiation and growth

Q5. Explain the role of vitamin A in vision. In the rod cells of the retina, 11-cis-retinal is bound to the protein opsin to form the visual pigment rhodopsin. When light strikes the retina, 11-cis-retinal is isomerized to all-trans-retinal, causing a conformational change in rhodopsin that triggers the visual signal (nerve impulse). The all-trans-retinal is then released and recycled back to 11-cis-retinal. This is the visual cycle. Vitamin A deficiency impairs this cycle, causing night blindness (nyctalopia).

Q6. What are the clinical features of vitamin A deficiency?

Early: Night blindness (nyctalopia) - earliest sign
Xerophthalmia: conjunctival dryness → Bitot's spots (triangular foamy patches on conjunctiva) → corneal ulceration and scarring (keratomalacia) → blindness
Hyperkeratosis of skin (follicular keratosis - "toad skin")
Increased susceptibility to infections (impaired immunity due to loss of epithelial integrity)
In children: growth retardation

Q7. What is hypervitaminosis A? Vitamin A toxicity from excess intake. Acute toxicity: nausea, vomiting, headache, increased intracranial pressure. Chronic toxicity: alopecia, dry scaly skin, hepatomegaly, bone pain/fractures, hyperlipidemia. Teratogenic - contraindicated in pregnancy (causes neural tube and craniofacial defects).

Vitamin D (Calciferol)

Q8. What are the two major forms of vitamin D and their sources?

Vitamin D2 (ergocalciferol): derived from ergosterol in plants/fungi by UV irradiation
Vitamin D3 (cholecalciferol): synthesized in human skin from 7-dehydrocholesterol by UV-B radiation (sunlight)

Q9. Describe the metabolism (activation) of vitamin D. Vitamin D3 is biologically inactive and requires two hydroxylation steps:

First hydroxylation in the liver: 25-hydroxylase converts D3 → 25-hydroxycholecalciferol (25-OH-D3 = calcidiol) - this is the major circulating storage form
Second hydroxylation in the kidney: 1α-hydroxylase converts 25-OH-D3 → 1,25-dihydroxycholecalciferol (calcitriol) = the biologically active form

1α-hydroxylase is stimulated by PTH, low calcium, low phosphate and inhibited by FGF-23.

Q10. What are the functions of active vitamin D (calcitriol)?

Increases calcium and phosphate absorption from the intestine (stimulates calcium-binding protein/calbindin synthesis)
Stimulates calcium reabsorption in the renal tubules
Acts with PTH on bone to stimulate osteoclast activity (bone resorption) → raises serum calcium
Inhibits PTH secretion (negative feedback)
Promotes cell differentiation

Q11. What diseases result from vitamin D deficiency?

Rickets (in children): softening and deformity of bones - bowing of legs, rachitic rosary, craniotabes, delayed fontanelle closure, hypocalcemia, tetany
Osteomalacia (in adults): soft, painful bones due to undermineralization of osteoid
Hypocalcemic tetany

Q12. What is the difference between rickets and osteoporosis?

Rickets/Osteomalacia: defective mineralization of bone matrix (osteoid) - bone is soft; due to vitamin D or calcium deficiency
Osteoporosis: reduced bone mass but normally mineralized bone; due to estrogen deficiency, aging, inactivity

Vitamin E (Tocopherol)

Q13. What is the biological function of vitamin E? Vitamin E is the most important fat-soluble antioxidant. It protects polyunsaturated fatty acids (PUFAs) in membrane phospholipids from lipid peroxidation by free radicals. It donates a hydrogen atom to lipid peroxyl radicals, breaking the chain reaction of oxidative damage. Vitamin C can regenerate vitamin E from the tocopherol radical.

Q14. What are the clinical features of vitamin E deficiency?

Hemolytic anemia in newborns (especially premature infants) - due to fragility of RBC membranes
Neurological abnormalities: peripheral neuropathy, spinocerebellar degeneration, ataxia, loss of deep tendon reflexes
Retinopathy
Deficiency is rare in adults but occurs in conditions with fat malabsorption (e.g., abetalipoproteinemia, cholestatic liver disease)

Vitamin K

Q15. What are the forms of vitamin K?

K1 (phylloquinone): from green leafy vegetables
K2 (menaquinone): synthesized by intestinal bacteria
K3 (menadione): synthetic form

Q16. What is the biochemical role of vitamin K? Vitamin K is the coenzyme for γ-glutamyl carboxylase, an enzyme that carboxylates specific glutamate residues in vitamin K-dependent clotting factors (II, VII, IX, X) and anticoagulant proteins C and S. This gamma-carboxylation creates Gla (γ-carboxyglutamate) residues that are essential for calcium-binding and activation of these clotting factors. During this reaction, the reduced form (KH2) is oxidized to epoxide (K epoxide), which is then recycled by vitamin K epoxide reductase - the enzyme inhibited by warfarin.

Q17. What are the clinical features of vitamin K deficiency?

Prolonged bleeding, easy bruising
Hemorrhagic disease of the newborn (neonates lack gut bacteria, low stores)
Prolonged PT (prothrombin time) and aPTT
Treatment: vitamin K injection (prophylactically given to all newborns)

Part 3: Water-Soluble Vitamins

Vitamin B1 (Thiamine)

Q18. What is the active coenzyme form of thiamine and its role? Active form: Thiamine pyrophosphate (TPP) / Thiamine diphosphate (TDP)

TPP is the coenzyme for three key multienzyme complexes involved in oxidative decarboxylation:

Pyruvate dehydrogenase (pyruvate → acetyl-CoA)
α-Ketoglutarate dehydrogenase (in the TCA cycle)
Branched-chain α-keto acid dehydrogenase (metabolism of leucine, isoleucine, valine)

TPP is also the coenzyme for transketolase in the pentose phosphate pathway.

Q19. What are the clinical manifestations of thiamine deficiency? Three distinct syndromes:

Dry beriberi: Peripheral neuropathy (symmetric sensorimotor polyneuropathy), muscle weakness
Wet beriberi: High-output cardiac failure with edema (cardiomegaly, tachycardia, peripheral edema) due to increased cardiac demand from peripheral vasodilation
Wernicke-Korsakoff syndrome: Associated with alcoholism; Wernicke's encephalopathy (ophthalmoplegia, ataxia, confusion) + Korsakoff psychosis (anterograde amnesia, confabulation)

Q20. How is thiamine nutritional status assessed in the lab? Erythrocyte transketolase activation test - the activity of transketolase in RBC lysate is measured before and after addition of thiamine diphosphate. An activation coefficient >1.25 indicates deficiency.

Q21. Why does thiamine deficiency produce lactic acidosis? Thiamine diphosphate is required by pyruvate dehydrogenase. In deficiency, pyruvate cannot be converted to acetyl-CoA. This leads to accumulation of pyruvate, which is reduced to lactate, causing elevated blood lactate and lactic acidosis. This is particularly life-threatening in patients on high carbohydrate diets.

Vitamin B2 (Riboflavin)

Q22. What coenzymes are derived from riboflavin?

FMN (Flavin Mononucleotide): formed by ATP-dependent phosphorylation of riboflavin
FAD (Flavin Adenine Dinucleotide): formed by further reaction with ATP

Both FMN and FAD are electron carriers in oxidoreduction reactions in the mitochondrial respiratory chain, β-oxidation of fatty acids, amino acid oxidation, and the TCA cycle.

Q23. What are the features of riboflavin deficiency (ariboflavinosis)?

Cheilosis (cracking at corners of mouth)
Angular stomatitis
Glossitis (magenta tongue)
Seborrheic dermatitis (especially nasolabial folds)
Normochromic normocytic anemia (or sometimes arachnomic) Note: Riboflavin deficiency alone is not fatal due to efficient tissue conservation and recycling of the coenzyme.

Q24. How is riboflavin status assessed? Erythrocyte glutathione reductase activation test - the enzyme is assayed before and after addition of FAD in vitro.

Vitamin B3 (Niacin)

Q25. Why is niacin "not strictly a vitamin"? Because niacin can be synthesized endogenously from the essential amino acid tryptophan. 60 mg of tryptophan is equivalent to 1 mg of dietary niacin. The niacin content of foods is therefore expressed as "niacin equivalents" = mg preformed niacin + (1/60 × mg tryptophan).

Q26. What coenzymes are derived from niacin?

NAD (Nicotinamide Adenine Dinucleotide)
NADP (Nicotinamide Adenine Dinucleotide Phosphate)

Both function as electron carriers in oxidation-reduction reactions across metabolism. NAD is also the substrate for ADP-ribosylation of proteins and poly-ADP-ribosylation in DNA repair. Cyclic ADP-ribose derived from NAD acts as an intracellular second messenger for calcium signaling.

Q27. What is pellagra? What are its features ("3 Ds + 1 D")? Pellagra is caused by deficiency of both niacin and tryptophan. Classic features:

Dermatitis: photosensitive rash on sun-exposed areas (Casal's necklace around neck)
Diarrhea
Dementia (depression, psychosis)
Death (if untreated)

Q28. In what diseases does pellagra occur despite adequate niacin/tryptophan intake?

Hartnup disease: rare genetic defect in intestinal/renal membrane transporter for tryptophan → malabsorption + renal wasting of tryptophan
Carcinoid syndrome: metastatic enterochromaffin tumor diverts tryptophan to serotonin synthesis, depleting niacin precursor
Isoniazid therapy: isoniazid (TB drug) inhibits B6, which is required for synthesis of niacin from tryptophan

Vitamin B6 (Pyridoxine)

Q29. What is the active coenzyme form of vitamin B6 and its roles? Active form: Pyridoxal phosphate (PLP)

PLP is the coenzyme for:

All aminotransferases (transamination reactions) - e.g., AST, ALT
Decarboxylases involved in neurotransmitter synthesis (DOPA → dopamine; 5-HTP → serotonin; glutamate → GABA; histidine → histamine)
Glycogen phosphorylase (glycogenolysis)
Synthesis of heme (δ-aminolevulinic acid synthase - first and rate-limiting step)
Synthesis of niacin from tryptophan

Q30. What are the features of B6 deficiency?

Seborrheic dermatitis
Microcytic anemia (sideroblastic pattern - impaired heme synthesis)
Glossitis
Peripheral neuropathy
Epileptiform convulsions (reduced GABA synthesis)
Rarely: depression, confusion
Caused by isoniazid, oral contraceptives, penicillamine (all bind PLP)

Q31. What is the toxicity of excess vitamin B6? Sensory neuropathy and peripheral neuropathy at doses of 2-7 g/day (pharmacological doses). Even 100-200 mg/day may cause neurological damage. This is notable because most water-soluble vitamins are considered non-toxic.

Q32. How is vitamin B6 status assessed? Erythrocyte transaminase activation test - measuring activation of erythrocyte AST or ALT by PLP added in vitro.

Vitamin B9 (Folic Acid / Folate)

Q33. What is the active coenzyme form of folate? Tetrahydrofolate (THF) - formed by two sequential reductions of folate by dihydrofolate reductase (DHFR), requiring NADPH. THF is the carrier of one-carbon units (methyl, methylene, formyl groups) in various metabolic reactions.

Q34. What are the key biochemical roles of folate?

Synthesis of purines (adenine, guanine) - provides formyl group
Synthesis of dTMP (thymidylate) from dUMP - methylene-THF donates methyl group via thymidylate synthase; DHFR regenerates THF
Remethylation of homocysteine to methionine (requires methyl-THF and vitamin B12)
Interconversion of serine and glycine

Q35. What are the consequences of folate deficiency?

Megaloblastic anemia: impaired DNA synthesis causes cells (especially rapidly dividing RBCs) to enlarge without dividing → large oval macrocytes, hypersegmented neutrophils
Neural tube defects (NTDs): in embryogenesis - anencephaly, spina bifida
Elevated homocysteine (risk factor for cardiovascular disease)
Note: No neurological symptoms (unlike B12 deficiency)

Q36. Why is folic acid supplementation important in pregnancy? Folate demand increases dramatically in early pregnancy for rapidly dividing fetal cells. Deficiency in the first 4 weeks of pregnancy (often before the woman knows she is pregnant) causes neural tube defects. Supplementation of 400 μg/day before conception and in the first trimester reduces NTD risk by ~70%.

Vitamin B12 (Cobalamin)

Q37. Describe the structure of vitamin B12. Vitamin B12 is a cobalt-containing compound with a corrin ring (similar to porphyrin but with one less methylene bridge). The central cobalt atom has four coordination bonds with the nitrogen atoms of the corrin ring, one with dimethylbenzimidazole nucleotide, and one variable - which may be cyano- (cyanocobalamin), methyl- (methylcobalamin), or 5'-deoxyadenosyl- (adenosylcobalamin).

Q38. What are the two active coenzyme forms of B12 and their roles?

Methylcobalamin (in cytosol): coenzyme for methionine synthase - transfers the methyl group from methyl-THF to homocysteine → methionine. This also regenerates THF (the "methyl-folate trap" concept)
Adenosylcobalamin (in mitochondria): coenzyme for methylmalonyl-CoA mutase - converts methylmalonyl-CoA → succinyl-CoA (part of odd-chain fatty acid and amino acid catabolism)

Q39. How is vitamin B12 absorbed? The pathway involves multiple binding proteins:

Gastric acid and pepsin release B12 from food
B12 binds cobalophilin (R-protein/haptocorrin) in saliva
In duodenum, pancreatic proteases hydrolyze cobalophilin, releasing B12
B12 binds intrinsic factor (IF) secreted by gastric parietal cells
The IF-B12 complex travels to the distal ileum where cubilin receptors absorb it
Inside enterocytes, B12 is transferred to transcobalamin II for blood transport

Q40. What are the features of B12 deficiency?

Megaloblastic anemia (identical to folate deficiency) - hypersegmented neutrophils, oval macrocytes
Subacute combined degeneration of the spinal cord (SACD): degeneration of posterior (dorsal) columns and lateral corticospinal tracts → loss of vibration sense, proprioception, spastic paraplegia. This is unique to B12 and does not occur in folate deficiency
Elevated methylmalonic acid (MMA) in urine - specific marker for B12 deficiency (not elevated in folate deficiency)
Elevated plasma homocysteine (shared with folate deficiency)

Q41. What is pernicious anemia? Autoimmune destruction of gastric parietal cells → loss of intrinsic factor → malabsorption of vitamin B12 → megaloblastic anemia + neurological disease. Confirmed by Schilling test (now largely replaced by serology: anti-parietal cell antibodies, anti-intrinsic factor antibodies) and serum B12 levels.

Q42. How do you differentiate B12 deficiency from folate deficiency?

Feature	B12 Deficiency	Folate Deficiency
Megaloblastic anemia	Yes	Yes
Neurological symptoms (SACD)	Yes	No
Methylmalonic acid (urine)	Elevated	Normal
Homocysteine	Elevated	Elevated
Serum B12	Low	Normal
Serum folate	Normal	Low

Key trap: Giving folate to a B12-deficient patient corrects the anemia but allows neurological damage to progress (masks the hematological sign of B12 deficiency).

Vitamin B7 (Biotin)

Q43. What is the biochemical role of biotin? Biotin is the coenzyme for all carboxylase enzymes (CO2 carrier). It is covalently attached to a lysine residue in these enzymes. Key biotin-dependent carboxylases:

Pyruvate carboxylase: Pyruvate → Oxaloacetate (anaplerosis, gluconeogenesis)
Acetyl-CoA carboxylase: Acetyl-CoA → Malonyl-CoA (first step in fatty acid synthesis)
Propionyl-CoA carboxylase: Propionyl-CoA → Methylmalonyl-CoA (odd-chain FA catabolism)
β-Methylcrotonyl-CoA carboxylase: leucine catabolism

Q44. What causes biotin deficiency?

Excessive consumption of raw egg whites: avidin (a glycoprotein in raw egg white) binds biotin with very high affinity and prevents its absorption. Cooking denatures avidin.
Long-term total parenteral nutrition without biotin supplementation
Antibiotic therapy (destroys gut bacteria which synthesize biotin)

Features: alopecia, dry scaly dermatitis, glossitis, conjunctivitis, CNS abnormalities (depression, hallucinations, hypotonia in infants).

Vitamin B5 (Pantothenic Acid)

Q45. What is the role of pantothenic acid? Pantothenic acid is a component of Coenzyme A (CoA) and the acyl carrier protein (ACP) of fatty acid synthase. CoA is central to:

Acetyl-CoA formation and entry into TCA cycle
Fatty acid synthesis and β-oxidation
Acetylation reactions
Cholesterol and steroid hormone synthesis

Deficiency is rare due to wide distribution in foods.

Vitamin C (Ascorbic Acid)

Q46. What is the biochemical function of vitamin C? Vitamin C acts as the coenzyme for two groups of hydroxylases:

Copper-containing hydroxylases: Vitamin C reduces Cu²⁺ back to Cu⁺ after hydroxylation (e.g., dopamine β-hydroxylase - norepinephrine synthesis; peptidylglycine hydroxylase - amidation of peptide hormones)
Fe²⁺-containing, α-ketoglutarate-linked hydroxylases (e.g., prolyl and lysyl hydroxylase for collagen synthesis; γ-butyrobetaine hydroxylase for carnitine synthesis)

It is also a powerful antioxidant and free radical scavenger, regenerates vitamin E from the tocopherol radical, and enhances non-heme iron absorption in the gut.

Q47. What are the features of scurvy (vitamin C deficiency)? All features relate to defective collagen synthesis (due to failure of proline and lysine hydroxylation):

Perifollicular hemorrhages and perifollicular hyperkeratosis (early skin signs)
Corkscrew hairs
Swollen, spongy, bleeding gums (gingivitis) - with loose teeth
Subperiosteal hemorrhages → bone pain; fragile capillaries → easy bruising
Poor wound healing
Sicca syndrome (dry eyes and mouth)
In infants (Barlow's disease): pain and swelling in joints, frog-leg posture, irritability

Q48. What is the relationship between vitamin C and iron absorption? Vitamin C (ascorbic acid) in the gut reduces Fe³⁺ (ferric) to Fe²⁺ (ferrous) form, which is more efficiently absorbed by the divalent metal transporter (DMT-1). It also forms a chelate complex with iron, keeping it soluble in the alkaline duodenum. This is why vitamin C-rich foods or supplements taken with meals can significantly increase non-heme iron absorption.

Q49. Why is vitamin C a vitamin for humans but not for most other animals? Humans (along with other primates, guinea pigs, and some fish/birds) lack the enzyme L-gulonolactone oxidase, which is the last step in the biosynthesis of ascorbic acid from glucose via the uronic acid pathway. Most other animals retain this enzyme and can synthesize their own vitamin C. This is an example of "relative dietary essentiality."

Part 4: High-Yield "Tricky" Viva Questions

Q50. Which vitamin is both a vitamin and a hormone? Vitamin D - calcitriol (1,25-dihydroxycholecalciferol) acts as a steroid hormone: it is synthesized in the body, travels through the blood, and acts on target organs via nuclear receptors to regulate gene expression.

Q51. Which vitamin deficiency causes both anemia AND neurological damage? Vitamin B12 - causes megaloblastic anemia AND subacute combined degeneration of the spinal cord (SACD). Folate deficiency also causes megaloblastic anemia but NOT neurological damage.

Q52. Name the vitamins that act as antioxidants.

Vitamin E (major lipid-soluble antioxidant - protects membrane PUFAs)
Vitamin C (water-soluble antioxidant; regenerates vitamin E)
Carotenoids (vitamin A precursors) - especially beta-carotene

Q53. Which vitamins are involved in one-carbon metabolism and homocysteine remethylation? Folate (as methyl-THF - donates methyl group) and Vitamin B12 (methylcobalamin - accepts methyl from methyl-THF and transfers to homocysteine). Vitamin B6 is also involved in the transsulfuration pathway (homocysteine → cysteine via cystathionine β-synthase).

Q54. What is the "methyl-folate trap"? When B12 is deficient, methionine synthase cannot function, so methyl-THF cannot donate its methyl group. All folate becomes "trapped" as methyl-THF and unavailable for other one-carbon reactions (including purine and thymidylate synthesis). This explains why B12 deficiency causes megaloblastic anemia that looks identical to folate deficiency - even if folate intake is adequate.

Q55. Which vitamins require FAD for their metabolism/activation?

Vitamin B6: flavin-dependent enzymes convert pyridoxine and pyridoxamine to pyridoxal (the active aldehyde form)
Folate: dihydrofolate reductase requires NADPH (not FAD directly)
Vitamin K: epoxide reductase (recycling)
Riboflavin deficiency can therefore secondarily impair B6 metabolism

Q56. What is the relationship between biotin and avidin? Avidin is a glycoprotein in raw egg white that binds biotin with very high affinity (one of the strongest known non-covalent interactions in biology - Kd ~10⁻¹⁵ M). This prevents biotin absorption, causing deficiency in people who eat large quantities of raw eggs. Cooking denatures avidin and eliminates this antagonism.

Q57. Name the fat-soluble vitamins that are teratogenic in excess. Vitamin A (retinoids) - excess causes craniofacial, cardiac, and neural tube defects. Isotretinoin (synthetic retinoid for acne) is highly teratogenic. Vitamin D excess causes hypercalcemia and calcinosis in the fetus.

Q58. What are the lab assessments for each B vitamin?

Vitamin	Lab Assessment
B1 (Thiamine)	Erythrocyte transketolase activation by TPP
B2 (Riboflavin)	Erythrocyte glutathione reductase activation by FAD
B6 (Pyridoxine)	Erythrocyte transaminase (AST) activation by PLP
B9 (Folate)	Serum/RBC folate; elevated homocysteine
B12 (Cobalamin)	Serum B12; elevated methylmalonic acid (MMA); homocysteine
Biotin	Plasma biotinidase activity; urinary biocytin

Sources: Harper's Illustrated Biochemistry, 32nd Ed. (Chapters 44, 45); Basic Medical Biochemistry: A Clinical Approach, 6th Ed.

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