N-Methylhistamin (Urin): the pathway in the body

N-Methylhistamin (Urin) is part of the pathway “Histamine”. This page shows the whole pathway; the station of N-Methylhistamin (Urin) is highlighted.

Where this laboratory value sits: N-methylhistamine — formed inside the cell. Cells absorb histamine. Inside, histamine N-methyltransferase transfers a methyl group from SAM to the molecule; this produces N-methylhistamine. This ends its action inside the cell. Source 4

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. If it builds up, it binds more receptors.

The pathway step by step

Each station states what the compound does there. Three signs: ↑ supplies — builds up or makes available · ↓ depletes — inhibits, consumes or withholds · ↕ both, depending on amount. Behind it stands what the statement rests on: established physiology, observed in studies, or contested. The signs do not grade; they name the direction.

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. Histamine acts on vessels, stomach, nerves and immune cells. Source 2, 1↕ both, depending on amount Histamine is a messenger with many tasks: it widens blood vessels, stimulates stomach acid, acts on wakefulness in the brain and steers immune cells. How it acts depends on amount, site and receptor. established physiology Source 3, 4
   ⚖ When the balance tips

   too much — If more histamine forms or arrives than DAO and HNMT break down, it builds up and acts at more receptors at once: vessels widen, gut movement increases, skin and mucous membranes react.

   too little — If little histamine is available, for example when histidine decarboxylase is absent, its signals are weaker; in animal models without this enzyme, immune cells respond differently.

   observed in studies · Source 4, 2

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. In this way the cell keeps a store ready. Source 3↑ supplies In the granules, histamine is bound to heparin and inactive. In this way the mast cell keeps a store ready that it can release within seconds when activated. established physiology Source 3
   ⚖ When the balance tips

   too much — If many mast cells with filled granules are present, a larger amount of histamine can be released at once on activation.

   too little — If the granules are emptied after a release, the cell needs time to form and store new histamine; until then it releases less.

   observed in studies · 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. Only now can histamine act. Source 3↑ supplies Release brings histamine to the receptors nearby; together with it, mast cells release further substances such as tryptase and heparin. Only now does stored histamine become active. established physiology Source 3
   ⚖ When the balance tips

   too much — If many mast cells are activated at once, histamine also enters the blood and acts on vessels throughout the body: they widen and let more fluid into the tissue.

   too little — If little is released, histamine stays bound in the granules, and its action is confined to the area around the cell or does not occur.

   established physiology · Source 3, 5

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. H1 widens vessels, for example, and H2 stimulates stomach acid. Source 3, 5↕ both, depending on amount H1 widens vessels, makes them more permeable and signals itch, H2 stimulates stomach acid, H3 slows the release of messengers in the nervous system, H4 steers immune cells. established physiology Source 3, 5
   ⚖ When the balance tips

   too much — If a lot of histamine is bound to H1, vessels widen, fluid passes into the tissue and nerve endings signal itch; at H2 more stomach acid is formed.

   too little — If the receptors are little occupied or blocked, for example by H1 antihistamines, these signals do not occur; in the brain, blocking H1 causes drowsiness.

   established physiology · Source 5, 3

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. This ends the action of this histamine. Source 4↓ depletes With this step, histamine outside the cells has been broken down. Imidazole acetic acid leaves the body in the urine. established physiology Source 4
   ⚖ When the balance tips

   too much — If a lot of histamine is broken down via DAO, more imidazole acetic acid forms; its amount follows turnover outside the cells.

   too little — If DAO works more slowly, less imidazole acetic acid forms, and more histamine stays free or is methylated inside the cell instead.

   established physiology · 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. In this way methylated histamine leaves the body. Source 4↓ depletes N-methylimidazole acetic acid is the end product of breakdown inside the cell. Through it, methylated histamine leaves the body in the urine. established physiology Source 4, 6
   ⚖ When the balance tips

   too much — If more histamine is formed and methylated, more N-MIAA appears in the urine; the amount follows turnover via the route inside the cell.

   too little — If MAO-B is inhibited or little FAD is available, more N-methylhistamine remains unchanged and appears as such in the urine.

   established physiology · Source 4, 6

Further stations

• Histidine — amino acid from food Histidine is an amino acid. It comes from dietary protein and from the turnover of the body's own proteins, and it is the starting material for histamine. Only a small part of it becomes histamine. Source 1↑ supplies Histidine is a building block of proteins and the starting material for histamine, carnosine and other substances. Only a small part of histidine goes into histamine formation. established physiology Source 1
  ⚖ When the balance tips

  too much — If a lot of histidine arrives, the liver breaks the excess down via urocanic acid to glutamate. How much histamine forms depends mainly on the amount of histidine decarboxylase.

  too little — If little histidine is available, the body draws on stores, for example carnosine in the muscles and haemoglobin.

  established physiology · Source 1, 2

• DAO — diamine oxidase, with copper Diamine oxidase is a copper-containing enzyme. Cells of the intestinal lining, the kidney and the placenta release it to the outside; it works outside the cells. It intercepts histamine from food in the gut. Source 4↓ depletes Diamine oxidase breaks histamine down outside the cells, above all in the gut. There it intercepts histamine from food before it reaches the blood. established physiology Source 4
  ⚖ When the balance tips

  too much — If a lot of DAO is active, free histamine in the gut is broken down quickly and little of it reaches the blood; in pregnancy the placenta forms particularly large amounts of DAO.

  too little — If little DAO is active, for example when medicines or alcohol inhibit it or copper is scarce, histamine from food is broken down more slowly and passes more readily into the blood.

  established physiology · Source 4

• Free histamine — outside the cells Outside the cells, histamine is present in free form. In the gut, histamine is added from foods and from bacteria that convert histidine; part of it can be detected in stool. It acts at receptors until DAO breaks it down. Source 4↕ both, depending on amount Free histamine acts at receptors in the gut wall and nearby until DAO breaks it down. Histamine from foods and from bacteria adds to the body's own amount. established physiology Source 4
  ⚖ When the balance tips

  too much — If more histamine arrives with food than DAO can break down, part of it passes through the gut wall into the blood and acts on vessels, skin and gut.

  too little — If little free histamine is present, the receptors nearby remain largely unoccupied; DAO then finds little substrate.

  established physiology · Source 4

• N-methylhistamine — formed inside the cell Cells absorb histamine. Inside, histamine N-methyltransferase transfers a methyl group from SAM to the molecule; this produces N-methylhistamine. This ends its action inside the cell. Source 4↓ depletes Methylation by HNMT ends the action of histamine inside the cell. In the brain and the airways, where there is hardly any DAO, it is the main breakdown route. established physiology Source 4
  ⚖ When the balance tips

  too much — If a lot of histamine is methylated inside the cell, more N-methylhistamine forms and more SAM is used up.

  too little — If little SAM is available or HNMT works more slowly, histamine inside the cell is broken down more slowly and acts there for longer.

  established physiology · Source 4

Cofactors in this pathway

• Histidine — Starting material from which histidine decarboxylase makes histamine; only a small part becomes histamine Source 1, 2In the ORY catalogue as a laboratory value: Histidin
• Vitamin B6 — Cofactor (PLP) of histidine decarboxylase; without PLP no histamine forms 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; without copper no DAO activity 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; with little of it, this breakdown stalls 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; without FAD this step stalls 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)
• IgE antibodies and mast cells — Histidin, Vitamin B6

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