Component
Prostaglandin H synthase reconstituted with manganese protoporphyrin, retaining cyclooxygenase but little peroxidase activity
Prostaglandin H synthase reconstituted with manganese protoporphyrin, retaining cyclooxygenase but little peroxidase activity. Species, exposure and limitations are retained in each linked claim.
2 recorded relationships. Experimental role, claim status and evidence remain attached to each record.
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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.
Other things that act on it
Enzymes, hormones, genes, and other components with a recorded effect. These are not nutrients, so they do not count toward the arrows above. Each finding names the chapter that recorded it.
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.
What acts on it
Higher concentrations of eugenol were required to inhibit iron-reconstituted prostaglandin H synthase than the manganese-reconstituted enzyme which retains cyclooxygenase but not peroxidase activity, inhibition was highly dependent on arachidonic acid concentration, adding 10 micromolar prostaglandin G2 did not prevent the inhibitory effects, and other phenolic compounds including guaiacol, butylated hydroxyanisole and acetaminophen inhibited the manganese enzyme similarly, demonstrating that these compounds specifically inhibit the cyclooxygenase component in addition to or independent of their effect on peroxide tone, which the authors suggest is due to competition with arachidonic acid for the active site.
Experimental context and source evidence
- evidence_span
- {"source_cache": "artifacts/paracetamol-research/2511429.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8dbe8c6f23fc857be6bba07e2a518c59f8dc76c9f8625c25ba84030c43f6e636", "start_char": 0, "end_char": 1593, "text_sha256": "8dbe8c6f23fc857be6bba07e2a518c59f8dc76c9f8625c25ba84030c43f6e636"}
- experimental_model
- Prostaglandin H synthase apoenzyme reconstituted with manganese or iron protoporphyrin
- exposure
- Eugenol, guaiacol, butylated hydroxyanisole and acetaminophen against both reconstituted forms, with prostaglandin G2 added
- limitations
- The manganese-reconstituted enzyme retains cyclooxygenase but little peroxidase activity, which is what lets this study separate the two proposed sites. Its conclusion is the opposite of the peroxide-tone account.
- 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
- In an enzyme stripped of its peroxidase the drug still works, which argues it also competes at the other site.
- primary_references
- [apap-p2511429] Mechanism of inhibition of prostaglandin H synthase by eugenol and other phenolic peroxidase substrates. (1989). https://pubmed.ncbi.nlm.nih.gov/2511429/ DOI: 10.1016/s0026-895x(25)09658-0
- tissue_or_cell_type
- Reconstituted prostaglandin H synthase
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prostaglandin H synthase apoenzyme reconstituted with manganese or iron protoporphyrin · source_derived_draft · unverified_draft
### apap-maybe-the-cox-site-instead Higher concentrations of eugenol were required to inhibit iron-reconstituted prostaglandin H synthase than the manganese-reconstituted enzyme which retains cyclooxygenase but not peroxidase activity, inhibition was highly dependent on arachidonic acid concentration, adding 10 micromolar prostaglandin G2 did not prevent the inhibitory effects, and other phenolic compounds including guaiacol, butylated hydroxyanisole and acetaminophen inhibited the manganese enzyme similarly, demonstrating that these compounds specifically inhibit the cyclooxygenase component in addition to or independent of their effect on peroxide tone, which the authors suggest is due to competition with arachidonic acid for the active site. 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: In an enzyme stripped of its peroxidase the drug still works, which argues it also competes at the other site. organism: Enzyme tissue_or_cell_type: Reconstituted prostaglandin H synthase experimental_model: Prostaglandin H synthase apoenzyme reconstituted with manganese or iron protoporphyrin limitations: The manganese-reconstituted enzyme retains cyclooxygenase but little peroxidase activity, which is what lets this study separate the two proposed sites. Its conclusion is the opposite of the peroxide-tone account. exposure: Eugenol, guaiacol, butylated hydroxyanisole and acetaminophen against both reconstituted forms, with prostaglandin G2 added evidence_span: {"source_cache": "artifacts/paracetamol-research/2511429.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8dbe8c6f23fc857be6bba07e2a518c59f8dc76c9f8625c25ba84030c43f6e636", "start_char": 0, "end_char": 1593, "text_sha256": "8dbe8c6f23fc857be6bba07e2a518c59f8dc76c9f8625c25ba84030c43f6e636"} [apap-p2511429] Mechanism of inhibition of prostaglandin H synthase by eugenol and other phenolic peroxidase substrates. (1989). https://pubmed.ncbi.nlm.nih.gov/2511429/ DOI: 10.1016/s0026-895x(25)09658-0
Complete structured claim and evidence
Where it participates (unsigned role)
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.
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
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.