TY - JOUR
T1 - Cytochrome P450s in the regulation of cellular retinoic acid metabolism
AU - Ross, A. Catharine
AU - Zolfaghari, Reza
PY - 2011/8/21
Y1 - 2011/8/21
N2 - 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.
AB - 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.
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U2 - 10.1146/annurev-nutr-072610-145127
DO - 10.1146/annurev-nutr-072610-145127
M3 - Article
C2 - 21529158
AN - SCOPUS:79960502781
SN - 0199-9885
VL - 31
SP - 65
EP - 87
JO - Annual Review of Nutrition
JF - Annual Review of Nutrition
ER -