Component

Long-chain acyl-CoA synthetase

Long-chain acyl-CoA synthetase. Species, exposure and limitations are retained in each linked claim.

3 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

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.

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

What it acts on

  1. The R enantiomers of 2-arylpropionic acids such as ibuprofen exhibit species- and substrate-dependent metabolic chiral inversion in which only R enantiomers are activated to acyl-CoA thioesters by an acyl-CoA synthetase via an adenylate intermediate, and those thioesters are the substrates for the epimerase responsible for chiral inversion; three internal peptide sequences of the purified 42 kilodalton epimerase showed 50% or more homology with regions of enzymes involved in fatty acid metabolism.

    Long-chain acyl-CoA synthetase → R(-)-ibuprofen source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/ibuprofen-research/8615858.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "16cf0cde21de3453912debe1cf25c6191784584aac6596a323e5b5c2944d74a5", "start_char": 0, "end_char": 1153, "text_sha256": "16cf0cde21de3453912debe1cf25c6191784584aac6596a323e5b5c2944d74a5"}
    experimental_model
    Purification of a 42 kilodalton epimerase from rat liver cytosol with polyclonal antibodies and peptide sequencing
    exposure
    R-enantiomers of 2-arylpropionic acids activated to acyl-CoA thioesters
    limitations
    States the activation asymmetry explicitly and provides the antibody used for tissue mapping. Peptide sequence homology is suggestive rather than functional evidence.
    nutrient_topic
    Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
    organism
    Rat and guinea pig
    plain_language
    The activating enzyme will only pick up the R hand, and that one fact explains the whole one-way chemistry.
    primary_references
    [ibu-p8615858] 2-Arylpropionyl-CoA epimerase: partial peptide sequences and tissue localization. (1995). https://pubmed.ncbi.nlm.nih.gov/8615858/ DOI: 10.1016/0006-2952(95)02054-3
    tissue_or_cell_type
    Liver and other tissues

    Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 123–134

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purification of a 42 kilodalton epimerase from rat liver cytosol with polyclonal antibodies and peptide sequencing · source_derived_draft · unverified_draft

    ### ibu-only-r-is-activated The R enantiomers of 2-arylpropionic acids such as ibuprofen exhibit species- and substrate-dependent metabolic chiral inversion in which only R enantiomers are activated to acyl-CoA thioesters by an acyl-CoA synthetase via an adenylate intermediate, and those thioesters are the substrates for the epimerase responsible for chiral inversion; three internal peptide sequences of the purified 42 kilodalton epimerase showed 50% or more homology with regions of enzymes involved in fatty acid metabolism. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The activating enzyme will only pick up the R hand, and that one fact explains the whole one-way chemistry. organism: Rat and guinea pig tissue_or_cell_type: Liver and other tissues experimental_model: Purification of a 42 kilodalton epimerase from rat liver cytosol with polyclonal antibodies and peptide sequencing limitations: States the activation asymmetry explicitly and provides the antibody used for tissue mapping. Peptide sequence homology is suggestive rather than functional evidence. exposure: R-enantiomers of 2-arylpropionic acids activated to acyl-CoA thioesters evidence_span: {"source_cache": "artifacts/ibuprofen-research/8615858.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "16cf0cde21de3453912debe1cf25c6191784584aac6596a323e5b5c2944d74a5", "start_char": 0, "end_char": 1153, "text_sha256": "16cf0cde21de3453912debe1cf25c6191784584aac6596a323e5b5c2944d74a5"} [ibu-p8615858] 2-Arylpropionyl-CoA epimerase: partial peptide sequences and tissue localization. (1995). https://pubmed.ncbi.nlm.nih.gov/8615858/ DOI: 10.1016/0006-2952(95)02054-3
    Complete structured claim and evidence

  2. Liver and kidney homogenates failed to invert R-ibuprofen directly even in the presence of all necessary cofactors, presumably from lack of enzymatic acyl-CoA synthesis, while the 2-arylpropionyl-CoA epimerase catalysed the transformation from either direction with high turnover and with greater catalytic efficiency for S-ibuprofen-CoA epimerization than for the R counterpart, so the acyl-CoA formation step assumes a pivotal role in controlling stereoselectivity and efficiency, and as the responsible synthetases differ between species the outcome varies: in guinea pigs the biotransformation proceeds in both directions with nearly equal efficiency whereas in humans it is virtually unidirectional and slow.

    Long-chain acyl-CoA synthetase → Metabolic chiral inversion of a 2-arylpropionic acid source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/ibuprofen-research/1859831.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "39dd843ee06ac569e1f2a3af9af6af1639e06694a0f8dcd280065c686bd9902f", "start_char": 0, "end_char": 2138, "text_sha256": "39dd843ee06ac569e1f2a3af9af6af1639e06694a0f8dcd280065c686bd9902f"}
    experimental_model
    Comparative in vivo studies across mammalian species with in vitro epimerization of chemically synthesised ibuprofen-CoA thioester
    exposure
    Synthetic R- and S-ibuprofen-CoA thioesters applied to tissue homogenates, with and without cofactors
    limitations
    The decisive control is the failure: homogenates could not invert free R-ibuprofen even with all cofactors, which locates the species difference in the activation step rather than in the epimerase.
    nutrient_topic
    Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
    organism
    Rat, guinea pig and human
    plain_language
    The one-way traffic is set by which enantiomer gets activated, not by the enzyme that does the flipping.
    primary_references
    [ibu-p1859831] Metabolic stereoisomeric inversion of ibuprofen in mammals. (1991). https://pubmed.ncbi.nlm.nih.gov/1859831/ DOI: 10.1016/0167-4838(91)90164-u
    tissue_or_cell_type
    Liver and kidney

    Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 110–121

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Comparative in vivo studies across mammalian species with in vitro epimerization of chemically synthesised ibuprofen-CoA thioester · source_derived_draft · unverified_draft

    ### ibu-the-synthetase-sets-direction Liver and kidney homogenates failed to invert R-ibuprofen directly even in the presence of all necessary cofactors, presumably from lack of enzymatic acyl-CoA synthesis, while the 2-arylpropionyl-CoA epimerase catalysed the transformation from either direction with high turnover and with greater catalytic efficiency for S-ibuprofen-CoA epimerization than for the R counterpart, so the acyl-CoA formation step assumes a pivotal role in controlling stereoselectivity and efficiency, and as the responsible synthetases differ between species the outcome varies: in guinea pigs the biotransformation proceeds in both directions with nearly equal efficiency whereas in humans it is virtually unidirectional and slow. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The one-way traffic is set by which enantiomer gets activated, not by the enzyme that does the flipping. organism: Rat, guinea pig and human tissue_or_cell_type: Liver and kidney experimental_model: Comparative in vivo studies across mammalian species with in vitro epimerization of chemically synthesised ibuprofen-CoA thioester limitations: The decisive control is the failure: homogenates could not invert free R-ibuprofen even with all cofactors, which locates the species difference in the activation step rather than in the epimerase. exposure: Synthetic R- and S-ibuprofen-CoA thioesters applied to tissue homogenates, with and without cofactors evidence_span: {"source_cache": "artifacts/ibuprofen-research/1859831.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "39dd843ee06ac569e1f2a3af9af6af1639e06694a0f8dcd280065c686bd9902f", "start_char": 0, "end_char": 2138, "text_sha256": "39dd843ee06ac569e1f2a3af9af6af1639e06694a0f8dcd280065c686bd9902f"} [ibu-p1859831] Metabolic stereoisomeric inversion of ibuprofen in mammals. (1991). https://pubmed.ncbi.nlm.nih.gov/1859831/ DOI: 10.1016/0167-4838(91)90164-u
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. In hepatocytes isolated from rats with adjuvant-induced arthritis the chiral inversion rate constant of R- to S-ibuprofen and the metabolic rate constants of both enantiomers were significantly decreased to about 64 to 80% of control values, while adding serum from each group abolished the difference; adjuvant-induced arthritis decreased messenger RNA levels of acyl-coenzyme A synthetase isoforms but not of 2-arylpropionyl-CoA epimerase, and chiral inversion was inhibited by triacsin C, a specific inhibitor of acyl-CoA synthetase 1.

    Adjuvant-induced arthritis in the rat → Metabolic chiral inversion of a 2-arylpropionic acid source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/ibuprofen-research/18988084.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "49f5377220f47f04a74dc5e1cd5408a0b175eafbf602e536e57d80a9e8eb1f3a", "start_char": 0, "end_char": 1381, "text_sha256": "49f5377220f47f04a74dc5e1cd5408a0b175eafbf602e536e57d80a9e8eb1f3a"}
    experimental_model
    Freshly isolated hepatocytes from control rats and rats with adjuvant-induced arthritis
    exposure
    S- or R-ibuprofen incubated with hepatocytes, with and without serum, and with triacsin C
    limitations
    Tests whether the disease being treated changes the handling of the drug. Isolated hepatocytes, and the serum arm shows the effect disappears when serum is added back.
    nutrient_topic
    Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
    organism
    Rat
    plain_language
    The inflammation the drug is prescribed for slows down the step that makes the drug active.
    primary_references
    [ibu-p18988084] Impaired intrinsic chiral inversion activity of ibuprofen in rats with adjuvant-induced arthritis. (2008). https://pubmed.ncbi.nlm.nih.gov/18988084/ DOI: 10.1080/00498250802483768
    tissue_or_cell_type
    Hepatocytes
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 162–173

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Freshly isolated hepatocytes from control rats and rats with adjuvant-induced arthritis · source_derived_draft · unverified_draft

    ### ibu-arthritis-slows-inversion In hepatocytes isolated from rats with adjuvant-induced arthritis the chiral inversion rate constant of R- to S-ibuprofen and the metabolic rate constants of both enantiomers were significantly decreased to about 64 to 80% of control values, while adding serum from each group abolished the difference; adjuvant-induced arthritis decreased messenger RNA levels of acyl-coenzyme A synthetase isoforms but not of 2-arylpropionyl-CoA epimerase, and chiral inversion was inhibited by triacsin C, a specific inhibitor of acyl-CoA synthetase 1. Condition category: machinery_impairment nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The inflammation the drug is prescribed for slows down the step that makes the drug active. organism: Rat tissue_or_cell_type: Hepatocytes experimental_model: Freshly isolated hepatocytes from control rats and rats with adjuvant-induced arthritis limitations: Tests whether the disease being treated changes the handling of the drug. Isolated hepatocytes, and the serum arm shows the effect disappears when serum is added back. exposure: S- or R-ibuprofen incubated with hepatocytes, with and without serum, and with triacsin C evidence_span: {"source_cache": "artifacts/ibuprofen-research/18988084.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "49f5377220f47f04a74dc5e1cd5408a0b175eafbf602e536e57d80a9e8eb1f3a", "start_char": 0, "end_char": 1381, "text_sha256": "49f5377220f47f04a74dc5e1cd5408a0b175eafbf602e536e57d80a9e8eb1f3a"} [ibu-p18988084] Impaired intrinsic chiral inversion activity of ibuprofen in rats with adjuvant-induced arthritis. (2008). https://pubmed.ncbi.nlm.nih.gov/18988084/ DOI: 10.1080/00498250802483768
    Complete structured claim and evidence

In the sources

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

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

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