Cytochrome retinoic acid

Carotenoid oxidation products are also supposed to have detrimental effects in vivo. As mentioned earlier, they are suspected to be involved in the adverse effects of high doses of 3-carotene supplementation in smokers and asbestos workers (CARET and ATBC studies) and in smoke-exposed ferrets. The mechanisms potentially involved have been investigated in vitro. P-Apo-8 -carotenal, an eccennic cleavage oxidation product of P-carotene, was shown to be a strong inducer of CYPlAl in rats, whereas P-carotene was not active. Cytochrome P450 (CYP 450) enzymes thus induced could enhance the activation of carcinogens and the destruction of retinoic acid. ... 

Liu, C., Russell, R.M., and Wang, X.D., Exposing ferrets to cigarette smoke and a pharmacological dose of beta-carotene supplementation enhance in vitro retinoic acid catabolism in lungs via induction of cytochrome P450 enzymes, J. Nutr., 133, 173, 2003. 

A striking feature of the collection of human brain cytochrome P450s discussed in the present review is the obvious major classes they fall into. With the exception of CYP26A1, which appears to be alone in the retinoic acid metabolic pathway, all the other brain P450s, including those normally considered xenobiotic-metabolizing, are either involved in the metabolism (or synthesis, in the case of CYP51, the... 

Cytochrome P450 pathways in human brain retinoic acid... 

Ray WJ, Bain G, Yao M, Gottlieb DI. 1997. CYP26, a novel mammalian cytochrome P450, is induced by retinoic acid and defines a new family. J Biol Chem 272 18702-18708. 

White JA, Beckett-Jones B, Guo YD, Dilworth FJ, Bonasoro J, et al. 1997. cDNA cloning of human retinoic acid-metabolizing enzyme (hP450RAI) identifies a novel family of cytochromes P450. J Biol Chem 272 18538-18541. 

White JA, Ramshaw H, Taimi M, Stangle W, Zhang A, et al. 2000. Identification of the human cytochrome P450, P450RAI-2, which is predominantly expressed in the adult cerebellum and is responsible for all-trans-retinoic acid metabolism. Proc Natl Acad Sci USA 97 6403-6408. 

Zhang QY, Raner G, Ding XX, et al. Characterization of the cytochrome P450 CYP2J4-expression in rat small intestine and role in retinoic acid biotransformation from retinal. Arch Biochem Biophys 1998 353 257-264. 

Retinoic acid regulates its own synthesis from retinol in a variety of tissues by induction of LRAT this increases the rate of esterification of retinol, thereby decreasing the amount available for oxidation to retinoic acid (Kurlandsky et al., 1996). Retinoic acid also induces the cytochrome P450 that catalyzes oxidation to 4-oxo-retinoic acid, and regulates both its own synthesis and catabolism. 

In adults, excessive alcohol consumption reduces liver reserves of vitamin A, both as a result of alcoholic liver damage and also by induction of cytochrome P450 enzymes that catalyze the oxidation of retinol to retinoic acid (as also occurs with chronic use of barbiturates). However, chronic consumption of alcohol can also potentiate the toxicity of retinol (Section 2.5.1). 

ChenH, Howald WN, and Juchau MR (2000) Biosynthesis of all-fraws-retinoic acid from all-fraws-retinol catalysis ofall-trfl s-retinol oxidation by human P-450 cytochromes. Drug Metabolism and Disposal 28, 315-22. 

Leo MA, Lasker JM, Raucy JL, Kim Cl, BlackM, and Lieber CS (1989) Metabolism of retinol and retinoic acid by human liver cytochrome P450IIC8. Archives of Biochemistry and Biophysics 269,305-12. 

Abbreviations used in text AA, arachidonic acid AhR, aryl hydrocarbon receptor Amt, AhR nuclear translocator BR, bilirubin BV, biliverdin CYP1A1, cytochrome P4501A1 DRE, dioxin responsive element FICZ, 6-formylindolo(3,2b)carbazole HAH, halogenated aromatic hydrocarbon I3C, indole 3-carbinol ICZ, indolo-(3,2,-b)-carbazole PAH, polycyclic aromatic hydrocarbon RAR, retinoic acid receptor TCDD, 2,3,7,8-tetrachlorodi benzo-/>-dioxin Trp, tryptophan UGT 01, UDP-glucuronosy 1 transferase 01... 

McSorley LC, Daly AK. 2000. Identification of human cytochrome P450 isoforms that contribute to all-trans-retinoic acid 4-hydroxylation. Biochem. Pharmacol. 60 517-26... 

MacLean, G., Abu-Abed, S., Dolle, P., Tahayato, A., Chambon, P., Petkovich, M. 2001. Cloning of a novel retinoic-acid metabolizing cytochrome P450, Cyp26Bl, and comparative expression analysis with Cyp26Al during early murine development. Mech. Dev. 107, 195-201. 

Li X-Y, Astrom A, Duell EA, et al. 1995. Retinoic acid antagonizes basal as well as coal tar and glucocorticoid-induced cytochrome P4501A1 expression in human skin. Carcinogenesis 16(3) 519-524. 

Marill, J., Cresteil, T., Lanotte, M., and Chabot, G. G. (2000) Identification of human cytochrome P450s involved in the formation of -trans-retinoic acid principal metabolites. Mol. Pharmacol. 58, 1341-1348. 

Leo, M.A., S. lida, and C.S. Lieber (1984). Retinoic acid metabolism by a system reconstituted with cytochrome P-450. Arch. Biochem. Biophys. 234, 305-312. 

Martini, R., A.M. Butler, X.M. Jiang, and M. Murray (1995). Pretranslational down regulation of cytochrome P450 2C11 in vitamin A-deficient male rat liver Prevention by dietary inclusion of retinoic acid. J. Pharmacol. Exp. Ther. 273, 427-434. 

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