Cytochrome P450 26A1 and Cytochrome P450 26B1 (CYP26A1 and CYP26B1)

Cytochrome P450 26A1 and Cytochrome P450 26B1 are members of the CYP26 subfamily of cytochrome P450 monooxygenases that play essential roles in the oxidative metabolism of all-trans-retinoic acid (atRA), the active metabolite of vitamin A. Both enzymes convert atRA to hydroxylated metabolites (such as 4-hydroxy-RA, 18-hydroxy-RA, and 4-oxo-RA), thus regulating intracellular and tissue gradients of retinoic acid required for embryonic development, tissue morphogenesis, cell differentiation, and homeostasis. CYP26A1 is highly expressed in the liver and is the primary enzyme responsible for hepatic clearance of atRA, while CYP26B1 is more prominent in the placenta, ovary, cerebellum, and tissues with specialized regulatory requirements. Mutations or altered expression of these genes can result in developmental abnormalities and disease. Inhibition of CYP26A1 or CYP26B1 is therapeutically investigated to boost endogenous retinoic acid concentrations for clinical benefit, but safety challenges exist due to the requirement for precise retinoic acid homeostasis.

Other names

Cytochrome P450 family 26 subfamily A member 1Cytochrome P450 family 26 subfamily B member 1CYP26 familyatRA hydroxylase

Inhibitors prevent retinoic acid (atRA) metabolism, leading to increased tissue retinoic acid concentration. Agonists are not applicable; mechanism focuses on blocking enzyme activity rather than stimulating it.