Arsen: the pathway in the body

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

Where this laboratory value sits: Environmental arsenic — drinking water and food. Inorganic arsenic occurs in soils and groundwater and enters the body through drinking water and food. In seafood, arsenic is present mainly in organic forms. Source 1

In brief

Arsenic is a semi-metal found in soils, groundwater and foods. In the body inorganic arsenic is methylated by the enzyme AS3MT, and trivalent forms bind to sulfur groups of proteins.

The pathway step by step

1. Environmental arsenic → Arsenate and arsenite Inorganic arsenic occurs as arsenate (pentavalent) or as arsenite (trivalent). Arsenate resembles phosphate in structure, while arsenite binds to sulfur groups. Source 1, 4
2. Arsenate and arsenite → Into the gut cell Transporters Arsenate enters cells through phosphate transport routes, arsenite through aquaglyceroporins — channels that also pass glycerol — and through sugar transporters. Source 2
3. Into the gut cell → Arsenic in the blood From the gut wall arsenic reaches the blood and from there the liver and other tissues. Source 1, 2
4. Arsenic in the blood → Skin, hair, nails · Keratin Keratin, the protein of skin, hair and nails, holds many sulfur groups. Trivalent arsenic binds to them and stays bound there for a longer time. Source 1, 4
5. Arsenite in the cell → MMA(V) AS3MT · SAM The enzyme AS3MT transfers a methyl group from SAM onto arsenite, forming monomethylarsonic acid. Source 3
6. MMA(V) → MMA(III) · Glutathione Glutathione and related sulfur compounds reduce MMA(V) to the trivalent form MMA(III), which AS3MT can methylate a second time. Source 3, 1
7. MMA(III) → DMA(V) AS3MT · SAM A second methyl group from SAM leads to dimethylarsinic acid. It is the form that predominates in urine. Source 3, 1
8. DMA(V) → Excretion in urine Methylated forms leave the cell through transport proteins and are excreted by the kidney; part of them passes with bile into the gut. Source 2
9. Arsenite in the cell → Binding to thiols Trivalent arsenic binds with high preference to sulfur groups (thiols) of proteins and to glutathione; neighbouring thiols are held especially firmly. Source 4
10. Binding to thiols → Lipoic acid The lipoic acid of the pyruvate dehydrogenase complex carries two adjacent sulfur groups — exactly the arrangement that trivalent arsenic binds. Source 5
11. Pyruvate → Acetyl-CoA PDH complex · Lipoic acid The pyruvate dehydrogenase complex converts pyruvate into acetyl-CoA. While the lipoic acid is occupied by trivalent arsenic, this conversion runs more slowly. Source 5

Cofactors in this pathway

• SAM (S-adenosylmethionine) — Methyl group donor of AS3MT, which methylates arsenite twice Source 3
• Glutathione — Reduces MMA(V) to MMA(III) and binds trivalent arsenic through its sulfur group Source 1, 3In the ORY catalogue as a laboratory value: Glutathion (GSH)
• Folate — Supplies methyl groups in one-carbon metabolism for the formation of SAM Source 6In the ORY catalogue as a laboratory value: Folsäure
• Vitamin B12 — Cofactor of methionine synthase, which regenerates methionine for the formation of SAM Source 6In the ORY catalogue as a laboratory value: Vitamin B12
• Methionine — Amino acid from which, with ATP, the methyl group donor SAM is formed Source 6In the ORY catalogue as a laboratory value: Methionin
• Lipoic acid — Carries two adjacent sulfur groups in the pyruvate dehydrogenase complex Source 5
• Selenium — Forms a joint compound with trivalent arsenic and glutathione that passes into bile Source 7In the ORY catalogue as a laboratory value: Selen

Sources

1. Watanabe T, Hirano S. Metabolism of arsenic and its toxicological relevance. Arch Toxicol 2013 · PubMed 22811022
2. Roggenbeck BA, Banerjee M, Leslie EM. Cellular arsenic transport pathways in mammals. J Environ Sci (China) 2016 · PubMed 28007179
3. Thomas DJ, Li J et al. Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals. Exp Biol Med (Maywood) 2007 · PubMed 17202581
4. Shen S, Li XF et al. Arsenic binding to proteins. Chem Rev 2013 · PubMed 23808632
5. Bergquist ER, Fischer RJ et al. Inhibition by methylated organo-arsenicals of the respiratory 2-oxo-acid dehydrogenases. J Organomet Chem 2009 · PubMed 20161290
6. Abuawad A, Bozack AK et al. Nutrition, one-carbon metabolism and arsenic methylation. Toxicology 2021 · PubMed 33905762
7. Ponomarenko O, La Porte PF et al. Selenium-mediated arsenic excretion in mammals: a synchrotron-based study of whole-body distribution and tissue-specific chemistry. Metallomics 2017 · PubMed 29058732

Whole pathway: Arsen

Related pathways

• Quecksilber — Glutathion (GSH), Methionin

As of 2026-09-18. Draft, written by Claude to schema v2; sources checked in PubMed; expert approval pending
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