Component

2-arylpropionyl-CoA epimerase

2-arylpropionyl-CoA epimerase. Species, exposure and limitations are retained in each linked claim.

6 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. Ibuprofen epimerization in humans is virtually irreversible from R to S, and 2-arylpropionyl-CoA epimerase readily converts R-ibuprofen-CoA into its S counterpart in active subcellular hepatic preparations, with examination of epimerase activity across tissues indicating that this metabolism occurs mainly in liver and kidney; reduced renal clearance together with metabolic bioactivation from inversion may raise plasma levels of the active species unpredictably.

    2-arylpropionyl-CoA epimerase → R-ibuprofenoyl-coenzyme A thioester source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/ibuprofen-research/1680979.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4888135fd1db1817c370825ee8a1435b7654e68af33912093c725fe7041341cc", "start_char": 0, "end_char": 1119, "text_sha256": "4888135fd1db1817c370825ee8a1435b7654e68af33912093c725fe7041341cc"}
    experimental_model
    Enantioselective high performance liquid chromatography in humans with active subcellular hepatic preparations from rats
    exposure
    Racemic and single-enantiomer ibuprofen, with R-ibuprofen-CoA applied to subcellular fractions
    limitations
    Establishes the epimerase step directly on the thioester. The tissue survey is in rat; the human arm is the demonstration that inversion is one-way.
    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
    Human and rat
    plain_language
    An enzyme flips the activated form from one hand to the other, mostly in the liver and kidney.
    primary_references
    [ibu-p1680979] Metabolic inversion of stereoisomeric ibuprofen in man. (1991). https://pubmed.ncbi.nlm.nih.gov/1680979/
    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 97–108

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enantioselective high performance liquid chromatography in humans with active subcellular hepatic preparations from rats · source_derived_draft · unverified_draft

    ### ibu-epimerase-acts-on-the-thioester Ibuprofen epimerization in humans is virtually irreversible from R to S, and 2-arylpropionyl-CoA epimerase readily converts R-ibuprofen-CoA into its S counterpart in active subcellular hepatic preparations, with examination of epimerase activity across tissues indicating that this metabolism occurs mainly in liver and kidney; reduced renal clearance together with metabolic bioactivation from inversion may raise plasma levels of the active species unpredictably. 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: An enzyme flips the activated form from one hand to the other, mostly in the liver and kidney. organism: Human and rat tissue_or_cell_type: Liver and kidney experimental_model: Enantioselective high performance liquid chromatography in humans with active subcellular hepatic preparations from rats limitations: Establishes the epimerase step directly on the thioester. The tissue survey is in rat; the human arm is the demonstration that inversion is one-way. exposure: Racemic and single-enantiomer ibuprofen, with R-ibuprofen-CoA applied to subcellular fractions evidence_span: {"source_cache": "artifacts/ibuprofen-research/1680979.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4888135fd1db1817c370825ee8a1435b7654e68af33912093c725fe7041341cc", "start_char": 0, "end_char": 1119, "text_sha256": "4888135fd1db1817c370825ee8a1435b7654e68af33912093c725fe7041341cc"} [ibu-p1680979] Metabolic inversion of stereoisomeric ibuprofen in man. (1991). https://pubmed.ncbi.nlm.nih.gov/1680979/
    Complete structured claim and evidence

  2. The purified 2-arylpropionyl-CoA epimerases from rat liver cytosol and mitochondria are monomeric 42 kilodalton proteins distinct from methylmalonyl-CoA epimerase, show no bound cofactors and are unaffected by EDTA or metal ions except copper, and for 2-(4-isobutylphenyl)propionyl-CoA the equilibrium constant was estimated at 1.5 in favour of the R isomer, with evidence that proton exchange is mediated by a two-base mechanism and that an active-site carboxylic residue serves as a general base for proton abstraction.

    2-arylpropionyl-CoA epimerase → Metabolic chiral inversion of a 2-arylpropionic acid source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/ibuprofen-research/8381432.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9fab6c9ed036c30f7dbfa01fd8499243d7066dfb510489f189a07ac4811c8ff6", "start_char": 0, "end_char": 1149, "text_sha256": "9fab6c9ed036c30f7dbfa01fd8499243d7066dfb510489f189a07ac4811c8ff6"}
    experimental_model
    Purification and kinetic characterisation of 2-arylpropionyl-CoA epimerase from rat liver cytosol and mitochondria
    exposure
    2-(4-isobutylphenyl)propionyl-CoA and related thioesters
    limitations
    Characterises the enzyme as a distinct protein and measures the equilibrium. Purified enzyme, so the equilibrium constant is a property of the epimerase and not of the intact animal.
    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
    Left to itself the enzyme slightly prefers the R form, which is the opposite of what happens in the body.
    primary_references
    [ibu-p8381432] Purification and characterization of novel "2-arylpropionyl-CoA epimerases" from rat liver cytosol and mitochondria. (1993). https://pubmed.ncbi.nlm.nih.gov/8381432/ DOI: 10.1016/s0021-9258(18)53720-0
    tissue_or_cell_type
    Liver cytosol and mitochondria

    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 136–147

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purification and kinetic characterisation of 2-arylpropionyl-CoA epimerase from rat liver cytosol and mitochondria · source_derived_draft · unverified_draft

    ### ibu-equilibrium-favours-r The purified 2-arylpropionyl-CoA epimerases from rat liver cytosol and mitochondria are monomeric 42 kilodalton proteins distinct from methylmalonyl-CoA epimerase, show no bound cofactors and are unaffected by EDTA or metal ions except copper, and for 2-(4-isobutylphenyl)propionyl-CoA the equilibrium constant was estimated at 1.5 in favour of the R isomer, with evidence that proton exchange is mediated by a two-base mechanism and that an active-site carboxylic residue serves as a general base for proton abstraction. 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: Left to itself the enzyme slightly prefers the R form, which is the opposite of what happens in the body. organism: Rat tissue_or_cell_type: Liver cytosol and mitochondria experimental_model: Purification and kinetic characterisation of 2-arylpropionyl-CoA epimerase from rat liver cytosol and mitochondria limitations: Characterises the enzyme as a distinct protein and measures the equilibrium. Purified enzyme, so the equilibrium constant is a property of the epimerase and not of the intact animal. exposure: 2-(4-isobutylphenyl)propionyl-CoA and related thioesters evidence_span: {"source_cache": "artifacts/ibuprofen-research/8381432.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9fab6c9ed036c30f7dbfa01fd8499243d7066dfb510489f189a07ac4811c8ff6", "start_char": 0, "end_char": 1149, "text_sha256": "9fab6c9ed036c30f7dbfa01fd8499243d7066dfb510489f189a07ac4811c8ff6"} [ibu-p8381432] Purification and characterization of novel "2-arylpropionyl-CoA epimerases" from rat liver cytosol and mitochondria. (1993). https://pubmed.ncbi.nlm.nih.gov/8381432/ DOI: 10.1016/s0021-9258(18)53720-0
    Complete structured claim and evidence

  3. A complementary DNA clone encoding 2-arylpropionyl-CoA epimerase was isolated from rat liver, expressed in Escherichia coli and confirmed by measuring the rate of inversion of R-ibuprofenoyl-CoA, and significant amino acid sequence similarity was found with carnitine dehydratases from Caenorhabditis elegans at 41% and Escherichia coli at 27%, suggesting that this protein, characterised until then only for its role in drug transformation, has a function in lipid metabolism; the R enantiomer is described as inactive in terms of cyclooxygenase inhibition.

    2-arylpropionyl-CoA epimerase → Bacterial and nematode carnitine dehydratases source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/ibuprofen-research/9106621.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d2ece633650b8d636b2d0315b6d6486f618f7aae8a585c54558dffe344edf0cf", "start_char": 0, "end_char": 1607, "text_sha256": "d2ece633650b8d636b2d0315b6d6486f618f7aae8a585c54558dffe344edf0cf"}
    experimental_model
    Molecular cloning and bacterial expression of 2-arylpropionyl-CoA epimerase from a rat liver complementary DNA library
    exposure
    Expressed epimerase assayed by rate of inversion of R-ibuprofenoyl-CoA
    limitations
    Identifies the gene and, through its homology, suggests the enzyme is not a drug-metabolising enzyme at all. Sequence homology is an inference about function, not a demonstration.
    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 enzyme that activates this drug looks like an enzyme for handling fats, which is probably its real job.
    primary_references
    [ibu-p9106621] Molecular cloning and expression of a 2-arylpropionyl-coenzyme A epimerase: a key enzyme in the inversion metabolism of ibuprofen. (1997). https://pubmed.ncbi.nlm.nih.gov/9106621/ DOI: 10.1124/mol.51.4.576
    tissue_or_cell_type
    Liver

    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 149–160

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Molecular cloning and bacterial expression of 2-arylpropionyl-CoA epimerase from a rat liver complementary DNA library · source_derived_draft · unverified_draft

    ### ibu-the-enzyme-is-a-lipid-enzyme A complementary DNA clone encoding 2-arylpropionyl-CoA epimerase was isolated from rat liver, expressed in Escherichia coli and confirmed by measuring the rate of inversion of R-ibuprofenoyl-CoA, and significant amino acid sequence similarity was found with carnitine dehydratases from Caenorhabditis elegans at 41% and Escherichia coli at 27%, suggesting that this protein, characterised until then only for its role in drug transformation, has a function in lipid metabolism; the R enantiomer is described as inactive in terms of cyclooxygenase inhibition. 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 enzyme that activates this drug looks like an enzyme for handling fats, which is probably its real job. organism: Rat tissue_or_cell_type: Liver experimental_model: Molecular cloning and bacterial expression of 2-arylpropionyl-CoA epimerase from a rat liver complementary DNA library limitations: Identifies the gene and, through its homology, suggests the enzyme is not a drug-metabolising enzyme at all. Sequence homology is an inference about function, not a demonstration. exposure: Expressed epimerase assayed by rate of inversion of R-ibuprofenoyl-CoA evidence_span: {"source_cache": "artifacts/ibuprofen-research/9106621.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d2ece633650b8d636b2d0315b6d6486f618f7aae8a585c54558dffe344edf0cf", "start_char": 0, "end_char": 1607, "text_sha256": "d2ece633650b8d636b2d0315b6d6486f618f7aae8a585c54558dffe344edf0cf"} [ibu-p9106621] Molecular cloning and expression of a 2-arylpropionyl-coenzyme A epimerase: a key enzyme in the inversion metabolism of ibuprofen. (1997). https://pubmed.ncbi.nlm.nih.gov/9106621/ DOI: 10.1124/mol.51.4.576
    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

  2. 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

  3. 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

In the sources

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