# Tryptophan Metabolism > Tryptophan metabolism in MBBS Biochemistry: serotonin and melatonin synthesis, kynurenine pathway, niacin equivalence and 5-HIAA. - Canonical URL: https://prepelephant.com/topics/mbbs/biochemistry/tryptophan-metabolism - Exam / course: MBBS · Subject: Biochemistry - Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team - First published: 2026-10-02 - Last updated: 2026-10-02 - How to cite: "Tryptophan Metabolism", PrepElephant, https://prepelephant.com/topics/mbbs/biochemistry/tryptophan-metabolism ## Direct answer Tryptophan, the amino acid with the largest side chain and the smallest daily requirement, splits into two major routes: the serotonergic pathway (tryptophan hydroxylase adding BH4 to make 5-hydroxytryptophan, decarboxylated to serotonin, then N-acetylated and O-methylated in the pineal to melatonin) and the kynurenine pathway, which degrades the bulk of dietary tryptophan through indoleamine 2,3-dioxygenase and ends in nicotinamide adenine dinucleotide. About 60 mg of tryptophan yields the niacin equivalent of 1 mg, which is why pure tryptophan deficiency mimics pellagra. Serotonin itself is degraded to 5-hydroxyindoleacetic acid (5-HIAA), the urinary marker of carcinoid syndrome. ## What you must remember - **Tryptophan hydroxylase is rate-limiting** for serotonin and is BH4-dependent; the second step uses aromatic amino acid decarboxylase with pyridoxal phosphate, the same enzyme that makes dopamine and histamine. - **Kynurenine pathway handles roughly 95% of tryptophan catabolism**, starting with indoleamine 2,3-dioxygenase (IDO), which is induced by interferon-gamma — hence low tryptophan and high kynurenine in chronic infection and pregnancy-related immune tolerance. - **Kynurenic acid blocks NMDA and cholinergic receptors (neuroprotective)** while quinolinic acid agonises NMDA receptors (neurotoxic); their balance is discussed in Huntington disease and AIDS dementia. - **Niacin equivalence: 60 mg tryptophan = 1 mg niacin** — the conversion that fails in Hartnup disease and in vitamin B6 deficiency caused by isoniazid, producing pellagra-like dermatitis. - **Melatonin synthesis:** serotonin is N-acetylated by N-acetyltransferase (the rate-limiting, night-activated step) then O-methylated by HIOMT; the pineal is wired from the suprachiasmatic nucleus, so light suppresses melatonin. - **Carcinoid syndrome:** urinary 5-HIAA above roughly 25 mg per 24 hours (normal under about 8) supports the diagnosis; avoid banana, tomato and walnut for a day before collection, since they falsely raise it. - **Distribution of serotonin:** about 90% gut enterochromaffin cells, 8-10% platelets (which take it up but cannot synthesise it), under 2% brain — SSRI-related diarrhoea is gut-receptor pharmacology. ## A pellagra work-through from the ward A 40-year-old on antitubercular therapy for three months returns with a photosensitive rash in a Casal's necklace distribution, loose stools and irritability. Isoniazid has depleted pyridoxal phosphate, and the pyridoxine-dependent steps at kynureninase stall, so tryptophan cannot be converted to niacin; add a marginal cereal-based diet and the niacin equivalent pool collapses. The fix is layered: pyridoxine 10-25 mg daily with INH continued, oral nicotinamide 100 mg three times a day for the deficit, and a protein-adequate diet so tryptophan substrate returns. Contrast the same rash in Hartnup disease — a neutral amino acid transport defect affecting renal and intestinal handling — where neutral amino acids flood the urine and tryptophan malabsorption in the colon yields indole metabolites; there the treatment adds nicotinamide plus a high-protein diet, and neomycin to cut colonic indole production in severe cases. Both conditions teach one sentence worth writing in any answer: pellagra is a disease of the tryptophan-to-niacin economy, not merely of dietary niacin. ## High-yield viva angles Viva examiners first test the enzyme pair: tryptophan hydroxylase for serotonin, tyrosine hydroxylase for catecholamines — both BH4-dependent, both rate-limiting, easily confused under pressure. The second angle is "why is carcinoid 5-HIAA high but serotonin in platelets irrelevant" — carcinoid tumours, especially ileal with liver metastases, overflow serotonin into blood where platelets sequester it and monoamine oxidase in liver, lung and brain degrades the rest to 5-HIAA. The third is Indian and practical: jowar (sorghum)-heavy diets with excess leucine antagonise the tryptophan-niacin conversion, cited in Indian nutrition texts as a reason pellagra appeared in Deccan populations eating little maize. ## Frequently asked questions ### Which is the rate-limiting enzyme of serotonin synthesis? Tryptophan hydroxylase, which converts tryptophan to 5-hydroxytryptophan using tetrahydrobiopterin; decarboxylation to serotonin follows. ### How much tryptophan equals one milligram of dietary niacin? Approximately 60 mg of tryptophan provides 1 mg niacin equivalent, a conversion needing pyridoxine at the kynureninase step. ### Why does Hartnup disease cause pellagra-like features? The defective neutral amino acid transporter starves the body of absorbed tryptophan, cutting niacin equivalents, while unabsorbed tryptophan is converted by colonic bacteria to indoles. ### What regulates melatonin secretion acutely? N-acetyltransferase activity, driven by norepinephrine from sympathetic fibres in darkness and suppressed by light via the retinohypothalamic-suprachiasmatic pathway. ### Which urinary marker confirms carcinoid syndrome? Twenty-four-hour urinary 5-HIAA, typically well above 25 mg per day in classical carcinoid, collected after excluding dietary serotonin for a day.