12-hydroperoxyeicosatetraenoic acid: molecular mechanisms & dependencies

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

Human evidence only

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

Where it participates (unsigned role)

Increasing the peroxide product of the cyclooxygenase, prostaglandin G2, by elevating the concentration of either enzyme or substrate reverses the inhibitory action of acetaminophen, as does adding prostaglandin G2 itself, 0.3 micromolar 12-hydroperoxyeicosatetraenoic acid which is a major product of the platelet completely reverses the action on synthase-1, and inhibition in endothelial cells is abrogated by tert-butyl hydroperoxide, supporting the hypothesis that hydroperoxide concentration contributes to the cellular selectivity.
Ambient cellular hydroperoxide concentration → Paracetamol source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/paracetamol-research/12011469.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7e599890f658a63c52471fbc7e6853d7db6a5ecbe892241a39c8a633b3ab2d0d", "start_char": 0, "end_char": 1561, "text_sha256": "7e599890f658a63c52471fbc7e6853d7db6a5ecbe892241a39c8a633b3ab2d0d"}
experimental_model
Interleukin-1-alpha-stimulated human endothelial cells and human platelets compared, with hydroperoxide addition
exposure
Acetaminophen with 2 micromolar arachidonic acid, and with prostaglandin G2, 12-hydroperoxyeicosatetraenoic acid or tert-butyl hydroperoxide added back
limitations
The decisive record of the chapter: it measures a 435-fold difference between two human cell types, shows it is not isoform selectivity, and reverses it by adding the peroxide back.
nutrient_topic
Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. · Paracetamol
organism
Human
plain_language
Put the peroxide back and the drug stops working, which is why the platelet is untouched.
primary_references
[apap-p12011469] Determinants of the cellular specificity of acetaminophen as an inhibitor of prostaglandin H(2) synthases. (2002). https://pubmed.ncbi.nlm.nih.gov/12011469/ DOI: 10.1073/pnas.102588199
tissue_or_cell_type
Endothelium and platelets
trigger_kind
biomarker_context Imported condition classification; unverified.
Paracetamol: the enzyme it reduces rather than blocks, the isoform that turned out not to exist, the metabolite that carries the analgesia, and the metabolite that destroys the liver (2026-09-22) · lines 103–114
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Interleukin-1-alpha-stimulated human endothelial cells and human platelets compared, with hydroperoxide addition · source_derived_draft · unverified_draft
### apap-peroxide-reverses-it Increasing the peroxide product of the cyclooxygenase, prostaglandin G2, by elevating the concentration of either enzyme or substrate reverses the inhibitory action of acetaminophen, as does adding prostaglandin G2 itself, 0.3 micromolar 12-hydroperoxyeicosatetraenoic acid which is a major product of the platelet completely reverses the action on synthase-1, and inhibition in endothelial cells is abrogated by tert-butyl hydroperoxide, supporting the hypothesis that hydroperoxide concentration contributes to the cellular selectivity. Condition category: biomarker_context nutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. plain_language: Put the peroxide back and the drug stops working, which is why the platelet is untouched. organism: Human tissue_or_cell_type: Endothelium and platelets experimental_model: Interleukin-1-alpha-stimulated human endothelial cells and human platelets compared, with hydroperoxide addition limitations: The decisive record of the chapter: it measures a 435-fold difference between two human cell types, shows it is not isoform selectivity, and reverses it by adding the peroxide back. exposure: Acetaminophen with 2 micromolar arachidonic acid, and with prostaglandin G2, 12-hydroperoxyeicosatetraenoic acid or tert-butyl hydroperoxide added back evidence_span: {"source_cache": "artifacts/paracetamol-research/12011469.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7e599890f658a63c52471fbc7e6853d7db6a5ecbe892241a39c8a633b3ab2d0d", "start_char": 0, "end_char": 1561, "text_sha256": "7e599890f658a63c52471fbc7e6853d7db6a5ecbe892241a39c8a633b3ab2d0d"} [apap-p12011469] Determinants of the cellular specificity of acetaminophen as an inhibitor of prostaglandin H(2) synthases. (2002). https://pubmed.ncbi.nlm.nih.gov/12011469/ DOI: 10.1073/pnas.102588199
Complete structured claim and evidence
Salicylate inhibits prostaglandin H synthase-1 and -2 with a potency inversely related to ambient hydroperoxide concentrations and its inhibition of synthase-1 was prevented by 12-hydroperoxyeicosatetraenoic acid, but unlike typical phenolic inhibitors such as acetaminophen, salicylate was ineffective as a reducing cosubstrate for the peroxidase activity, implicating the cyclooxygenase site as its target; 12-HPETE does not prevent inhibition of the manganese-reconstituted enzyme by salicylate, indicating that reversal by hydroperoxides depends on electron transfer between the cyclooxygenase and peroxidase active sites.
Salicylate / salicylic acid → Paracetamol source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/paracetamol-research/12538810.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "23bbb8a6c280cfcae85e304695c2a93f2c748c804befc1e006f415f4f8dfaed0", "start_char": 0, "end_char": 1592, "text_sha256": "23bbb8a6c280cfcae85e304695c2a93f2c748c804befc1e006f415f4f8dfaed0"}
experimental_model
Prostaglandin H synthase inhibition by salicylate compared with phenolic inhibitors, using manganese-reconstituted enzyme
exposure
Salicylate and benzoic acid analogues, with 12-hydroperoxyeicosatetraenoic acid and prostaglandin G2
limitations
Recorded here because it separates paracetamol from salicylate mechanistically while showing both are peroxide-sensitive. The work is on salicylate, which is stated on the claim.
nutrient_topic
Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. · Paracetamol
organism
Enzyme
plain_language
Two drugs that both stop working when peroxide is high, reaching that point by different routes.
primary_references
[apap-p12538810] Inhibition of prostaglandin H2 synthases by salicylate is dependent on the oxidative state of the enzymes. (2003). https://pubmed.ncbi.nlm.nih.gov/12538810/ DOI: 10.1124/jpet.102.042853
tissue_or_cell_type
Prostaglandin H synthase
Paracetamol: the enzyme it reduces rather than blocks, the isoform that turned out not to exist, the metabolite that carries the analgesia, and the metabolite that destroys the liver (2026-09-22) · lines 168–179
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prostaglandin H synthase inhibition by salicylate compared with phenolic inhibitors, using manganese-reconstituted enzyme · source_derived_draft · unverified_draft
### apap-salicylate-is-not-a-cosubstrate Salicylate inhibits prostaglandin H synthase-1 and -2 with a potency inversely related to ambient hydroperoxide concentrations and its inhibition of synthase-1 was prevented by 12-hydroperoxyeicosatetraenoic acid, but unlike typical phenolic inhibitors such as acetaminophen, salicylate was ineffective as a reducing cosubstrate for the peroxidase activity, implicating the cyclooxygenase site as its target; 12-HPETE does not prevent inhibition of the manganese-reconstituted enzyme by salicylate, indicating that reversal by hydroperoxides depends on electron transfer between the cyclooxygenase and peroxidase active sites. Condition category: normal nutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. plain_language: Two drugs that both stop working when peroxide is high, reaching that point by different routes. organism: Enzyme tissue_or_cell_type: Prostaglandin H synthase experimental_model: Prostaglandin H synthase inhibition by salicylate compared with phenolic inhibitors, using manganese-reconstituted enzyme limitations: Recorded here because it separates paracetamol from salicylate mechanistically while showing both are peroxide-sensitive. The work is on salicylate, which is stated on the claim. exposure: Salicylate and benzoic acid analogues, with 12-hydroperoxyeicosatetraenoic acid and prostaglandin G2 evidence_span: {"source_cache": "artifacts/paracetamol-research/12538810.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "23bbb8a6c280cfcae85e304695c2a93f2c748c804befc1e006f415f4f8dfaed0", "start_char": 0, "end_char": 1592, "text_sha256": "23bbb8a6c280cfcae85e304695c2a93f2c748c804befc1e006f415f4f8dfaed0"} [apap-p12538810] Inhibition of prostaglandin H2 synthases by salicylate is dependent on the oxidative state of the enzymes. (2003). https://pubmed.ncbi.nlm.nih.gov/12538810/ DOI: 10.1124/jpet.102.042853
Complete structured claim and evidence

The events it takes part in

A mechanism often involves more than two components. These are the full events, with every participant and its role.

Situations it appears in

Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

Open hypotheses

Proposed ideas that involve this component. They are labeled as hypotheses and do not change any recorded statement.

This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

12-hydroperoxyeicosatetraenoic acid