Cytochrome P450s in the regulation of cellular retinoic acid metabolism.

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Ross AC, Zolfaghari R

Cytochrome P450s in the regulation of cellular retinoic acid metabolism.

Annu Rev Nutr. 2011 Aug 21;31:65-87. doi: 10.1146/annurev-nutr-072610-145127.

PubMed ID

21529158 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Vitamin A	Cytochrome P450 26A1	Protein	Humans	Unknown	Substrate Inducer	Details