ArticleThe Journal of biological chemistry2012
Stereoselective formation and metabolism of 4-hydroxy-retinoic Acid enantiomers by cytochrome p450 enzymes.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Continuum of Host-Gut Microbial Co-metabolism: Host CYP3A4/3A7 are Responsible for Tertiary Oxidations of Deoxycholate Species.Drug metabolism and disposition: the biological fate of chemicals · 2019Trial
- New Mechanistic Evidence for Perfluorodecanoic Acid (PFDA) Teratogenicity via CYP26A1-Mediated Retinoic Acid Metabolism and Signaling.Chemical research in toxicology · 2026Article
- A glucose-like metabolite deficient in diabetes inhibits cellular entry of SARS-CoV-2.Nature metabolism · 2022Article
- Analysis of vitamin A and retinoids in biological matrices.Methods in enzymology · 2020Article
- Modulation of retinoid signaling: therapeutic opportunities in organ fibrosis and repair.Pharmacology & therapeutics · 2020Review
- Biochemical and physiological importance of the CYP26 retinoic acid hydroxylases.Pharmacology & therapeutics · 2019Review
- Neonatal cytochrome P450 CYP3A7: A comprehensive review of its role in development, disease, and xenobiotic metabolism.Archives of biochemistry and biophysics · 2019Review
- Systematically Characterize the Anti-Alzheimer's Disease Mechanism of Lignans fromMolecules (Basel, Switzerland) · 2019Article
- Human cytochrome P450 enzymes 5-51 as targets of drugs and natural and environmental compounds: mechanisms, induction, and inhibition - toxic effects and benefits.Drug metabolism reviews · 2018Review
- CYP26C1 Is a Hydroxylase of Multiple Active Retinoids and Interacts with Cellular Retinoic Acid Binding Proteins.Molecular pharmacology · 2018Article
- Direct protein-protein interactions and substrate channeling between cellular retinoic acid binding proteins and CYP26B1.FEBS letters · 2016Article
- Human cytochrome P450 27C1 catalyzes 3,4-desaturation of retinoids.FEBS letters · 2016Article
- Identification of Tazarotenic Acid as the First Xenobiotic Substrate of Human Retinoic Acid Hydroxylase CYP26A1 and CYP26B1.The Journal of pharmacology and experimental therapeutics · 2016Article
- Improved Homology Model of the Human all-trans Retinoic Acid Metabolizing Enzyme CYP26A1.Molecules (Basel, Switzerland) · 2016Article
- Comparison of the ligand binding site of CYP2C8 with CYP26A1 and CYP26B1: a structural basis for the identification of new inhibitors of the retinoic acid hydroxylases.Journal of enzyme inhibition and medicinal chemistry · 2016Article
- Structural and kinetic basis of steroid 17α,20-lyase activity in teleost fish cytochrome P450 17A1 and its absence in cytochrome P450 17A2.The Journal of biological chemistry · 2015Article
- Induction of CYP26A1 by metabolites of retinoic acid: evidence that CYP26A1 is an important enzyme in the elimination of active retinoids.Molecular pharmacology · 2015Article
- Nitric oxide and interleukin-1β stimulate the proteasome-independent degradation of the retinoic acid hydroxylase CYP2C22 in primary rat hepatocytes.The Journal of pharmacology and experimental therapeutics · 2014Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
All-trans-retinoic acid (atRA), the major active metabolite of vitamin A, plays a role in many biological processes, including maintenance of epithelia, immunity, and fertility and regulation of apoptosis and cell differentiation. atRA is metabolized mainly by CYP26A1, but other P450 enzymes such as CYP2C8 and CYP3As also contribute to atRA 4-hydroxylation. Although the primary metabolite of atRA, 4-OH-RA, possesses a chiral center, the stereochemical course of atRA 4-hydroxylation has not been studied previously. (4S)- and (4R)-OH-RA enantiomers were synthesized and separated by chiral column HPLC. CYP26A1 was found to form predominantly (4S)-OH-RA. This stereoselectivity was rationalized via docking of atRA in the active site of a CYP26A1 homology model. The docked structure showed a well defined niche for atRA within the active site and a specific orientation of the β-ionone ring above the plane of the heme consistent with stereoselective abstraction of the hydrogen atom from the pro-(S)-position. In contrast to CYP26A1, CYP3A4 formed the 4-OH-RA enantiomers in a 1:1 ratio and CYP3A5 preferentially formed (4R)-OH-RA. Interestingly, CYP3A7 and CYP2C8 preferentially formed (4S)-OH-RA from atRA. Both (4S)- and (4R)-OH-RA were substrates of CYP26A1 but (4S)-OH-RA was cleared 3-fold faster than (4R)-OH-RA. In addition, 4-oxo-RA was formed from (4R)-OH-RA but not from (4S)-OH-RA by CYP26A1. Overall, these findings show that (4S)-OH-RA is preferred over (4R)-OH-RA by the enzymes regulating atRA homeostasis. The stereoselectivity observed in CYP26A1 function will aid in better understanding of the active site features of the enzyme and the disposition of biologically active retinoids.
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