Q3 LONG ANSWER 10M ★ High-yield

Describe the coenzyme forms, functions and deficiency manifestations of thiamine, riboflavin and niacin.

Biochemistry · 1st Professional — Pre-Clinical

Coenzyme form — thiamine pyrophosphate (TPP).

Function	Enzyme	Consequence of deficiency
Oxidative decarboxylation	Pyruvate dehydrogenase	Pyruvate and lactate accumulate → lactic acidosis
—	α-Ketoglutarate dehydrogenase	TCA cycle impaired
—	Branched-chain α-keto acid dehydrogenase	BCAA accumulate
Transketolase	HMP shunt	↓ NADPH and ribose; the basis of the diagnostic test
Nerve conduction	Membrane function	Peripheral neuropathy

Sources — whole grains, pulses, pork, yeast, nuts; destroyed by polishing rice, cooking and thiaminases in raw fish and betel nut
Requirement 0.5 mg per 1000 kcal; needs rise with carbohydrate intake
Body stores last only 2–3 weeks — deficiency appears quickly

Deficiency

Form	Features
Dry beri-beri	Peripheral neuropathy — symmetrical, sensory and motor, wrist and foot drop; wasting
Wet beri-beri	High-output cardiac failure, oedema, dyspnoea, warm extremities
Infantile beri-beri	2–3 months; aphonia (hoarse cry), cardiac failure, convulsions
Wernicke encephalopathy	Confusion, ophthalmoplegia, ataxia — the classical triad; alcoholics
Korsakoff psychosis	Anterograde amnesia with confabulation; often irreversible

Assessment — erythrocyte transketolase activity with the TPP effect; a rise over 25% on adding TPP indicates deficiency
Always give thiamine before glucose in an alcoholic or malnourished patient — a glucose load consumes the last thiamine and can precipitate Wernicke encephalopathy

Coenzymes — FMN and FAD; carry 2 hydrogen atoms
Enzymes — succinate dehydrogenase, acyl-CoA dehydrogenase, xanthine oxidase, glutathione reductase, and complexes I and II of the respiratory chain
Sources — milk, egg, liver, green leafy vegetables; destroyed by light, which is why milk should not stand in sunlight
Requirement 1.2–1.6 mg/day

Deficiency (ariboflavinosis)

Angular stomatitis and cheilosis — cracks at the angles of the mouth and on the lips
Glossitis — magenta-coloured tongue
Seborrhoeic dermatitis around the nose and scrotum
Corneal vascularisation and photophobia
Normocytic anaemia
Assessed by erythrocyte glutathione reductase activity coefficient

Coenzymes — NAD+ and NADP+; carry 2 electrons and 1 H+
NAD+ is used in catabolic (oxidative) reactions; NADPH in anabolic (reductive) ones
Involved in over 200 dehydrogenases

Synthesis from tryptophan

Tryptophan → Kynurenine pathway → Needs vitamin B6, B2 and iron → niacin

60 mg tryptophan = 1 mg niacin
Requirement 16–18 mg niacin equivalents/day
Sources — liver, meat, fish, groundnut, whole grains. Maize niacin is bound (niacytin) and unavailable unless treated with alkali — as in the traditional Mexican preparation of tortillas

Pellagra — the three Ds

Dermatitis — symmetrical, on sun-exposed areas; Casal's necklace around the neck; glove and boot distribution
Diarrhoea — with glossitis and stomatitis
Dementia — irritability, depression, confusion, psychosis
A fourth D — death if untreated
Secondary pellagra — Hartnup disease (tryptophan malabsorption), carcinoid syndrome (tryptophan diverted to serotonin), isoniazid (antagonises B6), alcoholism
Maize-eating populations are at particular risk — maize is low in both available niacin and tryptophan, and high in leucine, which inhibits the conversion

Nicotinic acid in pharmacological doses (1–3 g) lowers LDL and triglyceride and raises HDL more than any other drug; limited by cutaneous flushing, which aspirin reduces
Nicotinamide does not cause flushing and has NO lipid effect — the two forms are not interchangeable therapeutically
Beri-beri and pellagra are diseases of monotonous staple diets — polished rice and maize respectively; both are prevented by dietary diversity
Thiamine deficiency should be suspected in any alcoholic with confusion, and treated empirically — the cost of treating is trivial, the cost of missing it is permanent amnesia
Refeeding syndrome — thiamine demand rises sharply when carbohydrate feeding restarts; it must be given before and during refeeding
Riboflavin colours urine bright yellow, which is harmless but alarms patients who have not been warned

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