Organophosphate: the pathway in the body

This page shows the biochemical pathway of the substance Organophosphate: how it enters the body, which stations it passes and which steps it affects. Every statement has a source. The page describes general textbook knowledge and says nothing about any individual person.

In brief

Organophosphates are esters of phosphoric acid and are used as insecticides. In the liver they are converted into the oxon form, which binds to the active site of acetylcholinesterase.

The pathway step by step

1. Organophosphate → Uptake Organophosphates enter the body via the skin, the airways and the gut. They dissolve in fat and pass through cell membranes. Source 1
2. Uptake → Conversion in the liver Enzymes of the cytochrome P450 family exchange the sulfur atom in the molecule for oxygen. CYP1A2, CYP2B6 and CYP3A4 are mainly involved. Source 2, 4
3. Conversion in the liver → Oxon form CYP enzymes · NADPH, oxygen This yields the oxon form. It binds to the active site of esterases far more strongly than the parent compound does. Source 2, 1
4. Oxon form → Cleavage by PON1 Paraoxonase 1 (PON1) is bound to HDL particles in the blood and cleaves the oxon form. Two calcium ions sit in its active site. Carboxylesterases also bind the oxon form. Source 4, 5, 1
5. Cleavage by PON1 → Dialkyl phosphates PON1 · calcium Cleavage yields dialkyl phosphates such as dimethyl and diethyl phosphate. They are water-soluble and leave the body with the urine. Source 6
6. Acetylcholine → Choline + acetate acetylcholinesterase Acetylcholinesterase cleaves acetylcholine into choline and acetate. Choline is carried back into the nerve cell and joined into acetylcholine again there. Source 3

Cofactors in this pathway

• Calcium — Two calcium ions in the active site of paraoxonase 1, which cleaves the oxon form Source 5
• HDL cholesterol — Carries PON1 in the blood: the enzyme is bound to HDL particles Source 4, 5In the ORY catalogue as a laboratory value: HDL-Cholesterin
• NADPH — Supplies the electrons for the cytochrome P450 reaction that forms the oxon form Source 2
• Glutathione — Cofactor of the glutathione S-transferases that break down some organophosphates Source 1In the ORY catalogue as a laboratory value: Glutathion (GSH)
• Choline — Building block of acetylcholine and cleavage product of acetylcholinesterase Source 3
• Oxygen — Is exchanged for the sulfur atom of the molecule during conversion in the liver Source 2

Sources

1. Costa LG. Current issues in organophosphate toxicology. Clin Chim Acta 2006 · PubMed 16337171
2. Buratti FM, Volpe MT et al. CYP-specific bioactivation of four organophosphorothioate pesticides by human liver microsomes. Toxicol Appl Pharmacol 2003 · PubMed 12620367
3. Colović MB, Krstić DZ et al. Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr Neuropharmacol 2013 · PubMed 24179466
4. Furlong CE. Genetic variability in the cytochrome P450-paraoxonase 1 (PON1) pathway for detoxication of organophosphorus compounds. J Biochem Mol Toxicol 2007 · PubMed 17936934
5. Harel M, Aharoni A et al. Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes. Nat Struct Mol Biol 2004 · PubMed 15098021
6. Neves AP, Rosa ACS et al. Urinary dialkylphosphate metabolites in the assessment of exposure to organophosphate pesticides: from 2000 to 2022. Environ Monit Assess 2023 · PubMed 38049584

Related pathways

• DDT und DDE — conversion in the liver

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