title: Cytochrome P450s in the regulation of cellular retinoic acid metabolism.
abstract: The active metabolite of vitamin A, retinoic acid (RA), is a powerful regulator of gene transcription. RA is also a therapeutic drug. The oxidative metabolism of RA by certain members of the cytochrome P450 (CYP) superfamily helps to maintain tissue RA concentrations within appropriate bounds. The CYP26 family--CYP26A1, CYP26B1, and CYP26C1--is distinguished by being both regulated by and active toward all-trans-RA (at-RA) while being expressed in different tissue-specific patterns. The CYP26A1 gene is regulated by multiple RA response elements. CYP26A1 is essential for embryonic development, whereas CYP26B1 is essential for postnatal survival as well as germ cell development. Enzyme kinetic studies have demonstrated that several CYP proteins are capable of metabolizing at-RA; however, it is likely that CYP26A1 plays a major role in RA clearance. Thus, pharmacological approaches to limiting the activity of CYP26 enzymes may extend the half-life of RA and could be useful clinically in the future.
authors.affiliation: Department of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802, USA. Acr6@psu.edu
authors.forename: A Catharine
authors.initials: AC
authors.lastname: Ross
authors.forename: Reza
authors.initials: R
authors.lastname: Zolfaghari
mesh_terms: D000818:Animals; D055162:Biocatalysis; D001711:Biotransformation; D002454:Cell Differentiation; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D047108:Embryonic Development; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000201:enzymology / Q000378:metabolism; D000072516:Retinoic Acid 4-Hydroxylase; D047488:Retinoid X Receptors / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D007527:Isoenzymes; D047488:Retinoid X Receptors; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; C000607079:CYP26B1 protein, human; D000072516:Retinoic Acid 4-Hydroxylase