Melatonin: the pathway in the body

Melatonin is part of the pathway “Serotonin and melatonin”. This page shows the whole pathway; the station of Melatonin is highlighted.

Where this laboratory value sits: Melatonin — messenger of the night. The enzyme ASMT transfers a methyl group from SAM to N-acetylserotonin. Melatonin leaves the pineal gland and spreads through the body via the blood. Source 4

In brief

Serotonin and melatonin are messengers that the body makes from the amino acid tryptophan. Serotonin is formed in the gut lining and in nerve cells, melatonin at night in the pineal gland.

The pathway step by step

1. Tryptophan → 5-Hydroxytryptophan Tryptophan hydroxylase · BH4, Iron Tryptophan hydroxylase attaches an OH group to tryptophan. The enzyme contains iron and needs the cofactor tetrahydrobiopterin (BH4). This is the slowest step of the pathway. Source 1, 7
2. 5-Hydroxytryptophan → Serotonin AADC · Vitamin B6 (PLP) The enzyme AADC removes a carboxyl group from 5-HTP, using pyridoxal phosphate, the active form of vitamin B6. Serotonin is made in cells of the gut lining and in nerve cells. Source 2, 3
3. Serotonin → N-Acetylserotonin AANAT · Acetyl-CoA In the pineal gland, the enzyme AANAT attaches an acetyl group to serotonin at night. The amount of this enzyme follows the day-night rhythm. Source 4
4. N-Acetylserotonin → Melatonin ASMT · SAM The enzyme ASMT transfers a methyl group from SAM to N-acetylserotonin. Melatonin leaves the pineal gland and spreads through the body via the blood. Source 4
5. 6-Hydroxymelatonin → 6-Sulfatoxymelatonin Sulfotransferase A sulfotransferase attaches a sulphate group to 6-hydroxymelatonin. In this water-soluble form, the compound leaves the body in the urine. Source 4

Cofactors in this pathway

• Tetrahydrobiopterin (BH4) — Cofactor of tryptophan hydroxylase, which forms 5-HTP Source 1, 7
• Iron — Metal in the active site of tryptophan hydroxylase Source 1In the ORY catalogue as a laboratory value: Eisen
• Vitamin B6 — As pyridoxal phosphate, cofactor of AADC, which converts 5-HTP to serotonin Source 2In the ORY catalogue as a laboratory value: Vitamin B6
• Acetyl-CoA — Supplies AANAT with the acetyl group for N-acetylserotonin Source 4
• S-adenosylmethionine (SAM) — Methyl group donor for ASMT, which forms melatonin Source 4
• Vitamin B2 (FAD) — As FAD, cofactor of monoamine oxidase, which breaks down serotonin Source 6

Sources

1. Roberts KM, Fitzpatrick PF. Mechanisms of tryptophan and tyrosine hydroxylase. IUBMB Life 2013 · PubMed 23441081
2. Paiardini A, Giardina G, Rossignoli G et al. New Insights Emerging from Recent Investigations on Human Group II Pyridoxal 5'-Phosphate Decarboxylases. Curr Med Chem 2017 · PubMed 27881066
3. Jones LA, Sun EW, Martin AM et al. The ever-changing roles of serotonin. Int J Biochem Cell Biol 2020 · PubMed 32479926
4. Claustrat B, Leston J. Melatonin: Physiological effects in humans. Neurochirurgie 2015 · PubMed 25908646
5. Badawy AA. Kynurenine Pathway of Tryptophan Metabolism: Regulatory and Functional Aspects. Int J Tryptophan Res 2017 · PubMed 28469468
6. Edmondson DE, Binda C. Monoamine Oxidases. Subcell Biochem 2018 · PubMed 29464559
7. Werner ER, Blau N, Thöny B. Tetrahydrobiopterin: biochemistry and pathophysiology. Biochem J 2011 · PubMed 21867484

Whole pathway: Serotonin and melatonin

Related pathways

• Kynurenine pathway — tryptophan
• NAD⁺ — tryptophan
• Carnitine — Eisen, Vitamin B6
• Dopamine, noradrenaline, adrenaline — Eisen, Vitamin B6
• Spermidine — Eisen, Vitamin B6

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert review pending
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