Histamin: the pathway in the body

Histamin is part of the pathway “Histamine”. This page shows the whole pathway; the station of Histamin is highlighted.

Where this laboratory value sits: Histamine — in mast cells, basophils. The enzyme histidine decarboxylase removes a carboxyl group from histidine; this produces histamine. The enzyme needs pyridoxal phosphate, the active form of vitamin B6. Source 2, 1

In brief

Histamine is a messenger formed from the amino acid histidine and stored in mast cells. Once released it binds to four receptor types; it is broken down by diamine oxidase and by histamine N-methyltransferase.

The pathway step by step

1. Histidine → Histamine Histidine decarbox. · vitamin B6 (PLP) The enzyme histidine decarboxylase removes a carboxyl group from histidine; this produces histamine. The enzyme needs pyridoxal phosphate, the active form of vitamin B6. Source 2, 1
2. Histamine → Storage granules · heparin Mast cells and basophil blood cells store histamine in small vesicles. There it stays bound to heparin and has no effect on the outside. Source 3
3. Storage granules → Release When an antigen binds to IgE antibodies on the mast cell, or other stimuli act on it, the vesicles fuse with the cell membrane and release histamine to the outside. Source 3
4. Release → H1 to H4 receptors Histamine binds to four receptor types. Depending on type and tissue, they trigger different signals – on blood vessels, nerve cells, stomach cells and immune cells. Source 3, 5
5. Free histamine → Imidazole acetic acid DAO · copper Diamine oxidase removes the amino group. Via an aldehyde intermediate, imidazole acetic acid is formed and excreted in the urine. Source 4
6. N-methylhistamine → N-MIAA MAO-B, ALDH Monoamine oxidase B and an aldehyde dehydrogenase break N-methylhistamine down further. The end product appears in the urine. Source 4

Cofactors in this pathway

• Histidine — Starting material from which histidine decarboxylase makes histamine Source 1, 2In the ORY catalogue as a laboratory value: Histidin
• Vitamin B6 — Cofactor (PLP) of histidine decarboxylase Source 2In the ORY catalogue as a laboratory value: Vitamin B6
• Copper — Metal in the active site of diamine oxidase, which breaks histamine down outside cells Source 4In the ORY catalogue as a laboratory value: Kupfer (Cu)
• SAM (from methionine) — Donor of the methyl group for histamine N-methyltransferase inside the cell Source 4In the ORY catalogue as a laboratory value: Methionin
• Vitamin B2 (FAD) — Flavin cofactor of monoamine oxidase B, which breaks N-methylhistamine down further Source 6, 4

What acts on this pathway

• H1 antihistamines — Drugs in this group occupy the H1 receptor and hold it in its inactive form. Histamine can then no longer bind there; the other receptor types are not affected. Source 5

Sources

1. Brosnan ME, Brosnan JT. Histidine Metabolism and Function. J Nutr 2020 · PubMed 33000155
2. Moriguchi T, Takai J. Histamine and histidine decarboxylase: Immunomodulatory functions and regulatory mechanisms. Genes Cells 2020 · PubMed 32394600
3. Heidarzadeh-Asl S, Maurer M, Kiani A et al. Novel insights on the biology and immunologic effects of histamine: A road map for allergists and mast cell biologists. J Allergy Clin Immunol 2025 · PubMed 39734034
4. Maintz L, Novak N. Histamine and histamine intolerance. Am J Clin Nutr 2007 · PubMed 17490952
5. Simons FE, Simons KJ. Histamine and H1-antihistamines: celebrating a century of progress. J Allergy Clin Immunol 2011 · PubMed 22035879
6. Binda C, Mattevi A, Edmondson DE. Structural properties of human monoamine oxidases A and B. Int Rev Neurobiol 2011 · PubMed 21971000

Whole pathway: Histamine

Related pathways

• Calprotectin — release
• Dopamine, noradrenaline, adrenaline — Vitamin B6, Kupfer (Cu)
• Carnitine — Vitamin B6, Methionin
• Iron and ferritin — Vitamin B6, Kupfer (Cu)
• Spermidine — Vitamin B6, Methionin

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