Cytochrome P450 family 26 (CYP26) (CYP26)

The Cytochrome P450 family 26 (CYP26) consists of three main enzymes—CYP26A1, CYP26B1, and CYP26C1—that serve as the primary catabolic regulators of all-trans retinoic acid (atRA). As the active metabolite of Vitamin A, atRA is a critical signaling molecule that regulates gene expression, cell differentiation, and embryonic development. The CYP26 enzymes maintain RA homeostasis by hydroxylating atRA into inactive metabolites, thereby preventing excessive signaling and establishing essential morphogen gradients during morphogenesis. In clinical contexts, these enzymes are targeted by a class of drugs known as Retinoic Acid Metabolism Blocking Agents (RAMBAs) to increase endogenous atRA levels. This therapeutic strategy is explored for treating dermatological conditions like psoriasis and acne, as well as malignancies such as acute promyelocytic leukemia where rapid atRA clearance can lead to treatment resistance. However, pharmacological inhibition of the CYP26 family carries significant risks, most notably teratogenicity, due to the potent biological activity of retinoic acid in the developing fetus. Additionally, the potential for autoinduction of these enzymes can lead to metabolic resistance, complicating long-term therapeutic efficacy.

Other names

Retinoic acid hydroxylaseP450RAIRetinoic acid-metabolizing cytochrome P450Cytochrome P450 subfamily XXVIA

Inhibition of retinoic acid metabolism (Retinoic Acid Metabolism Blocking Agents - RAMBAs)