Retinoid production and catabolism: role of diet in regulating retinol esterification and retinoic Acid oxidation.
Retinoic acid (RA), a transcriptionally active metabolite of vitamin A (retinol), activates two families of nuclear retinoid receptors that have the potential to regulate the expression of a large number of genes. Although it may be presumed that the concentration of RA is closely regulated, the mechanisms underlying such regulation are not well understood. Our research has examined the expression and function of two enzymes, lecithin:retinol acyltransferase (LRAT) and a cytochrome P450, CYP26, in the liver and lung of rats and mice, over a wide range of vitamin A status or after treatment of vitamin A-deficient animals with exogenous RA. LRAT expression at both the mRNA and protein activity levels and CYP26 mRNA are regulated by dietary vitamin A in a steady-state model and are acutely regulated by RA in an acute repletion model. In the liver, the level of expression of LRAT and CYP26 is as follows: vitamin A deficient < vitamin A marginal < vitamin A adequate < vitamin A supplemented < RA treated. The regulation of LRAT shows strong tissue specificity (highly regulated in liver and lung but not in small intestine), whereas CYP26 is strongly regulated in the liver, lung, testis and intestine. RA may function as a signal of the body's vitamin A adequacy. The regulated expression of LRAT, CYP26 and other genes by RA may provide a sensitive response mechanism that overall serves to adjust the metabolism of vitamin A to maintain retinoid homeostasis and prevent retinoid excess.
Ross
A Catharine
AC
Department of Nutritional Sciences, The Pennsylvania State University, University Park 16802, USA. acr6@psu.edu
D000217:Acyltransferases / Q000235:genetics / Q000502:physiology; D000818:Animals; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006706:Homeostasis; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D051381:Rats; D014212:Tretinoin / Q000378:metabolism*; D014801:Vitamin A / Q000378:metabolism / Q000502:physiology
D014801:Vitamin A; D014212:Tretinoin; D000217:Acyltransferases; C056942:lecithin-retinol acyltransferase