Cytochrome P450 26A1

Definition:

A cytochrome P450 monooxygenase involved in the metabolism of all-trans retinoic acid (atRA), a signaling molecule that binds to retinoic acid receptors and regulates gene transcription. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase). Catalyzes the hydroxylation of carbon hydrogen bonds of atRA primarily at C-4 and C-18. Has no activity toward 9-cis and 13-cis retinoic acid stereoisomers. May play a role in the oxidative metabolism of xenobiotics such as tazarotenic acid.

References:

[1]. Ariel R Topletz, et al. Comparison of the function and expression of CYP26A1 and CYP26B1, the two retinoic acid hydroxylases. Biochem Pharmacol. 2012 Jan 1;83(1):149-63. [Content Brief]

[2]. J A White, et al. cDNA cloning of human retinoic acid-metabolizing enzyme (hP450RAI) identifies a novel family of cytochromes P450. J Biol Chem. 1997 Jul 25;272(30):18538-41. [Content Brief]

[3]. Robert S Foti, et al. Identification of Tazarotenic Acid as the First Xenobiotic Substrate of Human Retinoic Acid Hydroxylase CYP26A1 and CYP26B1. J Pharmacol Exp Ther. 2016 May;357(2):281-92. [Content Brief]

[4]. E Sonneveld, et al. Human retinoic acid (RA) 4-hydroxylase (CYP26) is highly specific for all-trans-RA and can be induced through RA receptors in human breast and colon carcinoma cells. Cell Growth Differ. 1998 Aug;9(8):629-37. [Content Brief]

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