描述
Retinol, the animal form of vitamin A, is a fat-soluble vitamin important in vision and bone growth. Retinol is among the most usable forms of vitamin A, which also include retinal (aldehyde form), retinoic acid (acid form) and retinyl ester (ester form). Retinol is normaly ingested in a precursor form. Typically animal sources (liver and eggs) contain retinyl esters, whereas plants (carrots, spinach) contain pro-vitamin A carotenoids. Hydrolysis of retinyl esters results in retinol, while pro-vitamin A carotenoids can be cleaved to produce retinal. Retinal (retinaldehyde) can be reversibly reduced to produce retinol or it can be irreversibly oxidized to produce retinoic acid. Retinoic acid is derived from retinol by oxidation through retinol and retinal dehydrogenases and several cytochrome p450s (CYPs). Many different geometric isomers of retinol, retinal and retinoic acid are possible as a result of either a trans or cis configuration of four of the five double bonds found in the polyene chain. The cis isomers are less stable and can readily convert to the all-trans configuration. Nevertheless, some cis isomers are found naturally and carry out essential functions. For example, the 11-cis-retinal isomer is the chromophore of rhodopsin, the vertebrate photoreceptor molecule. Retinoic acid plays an important role in regulating cell growth and differentiation. Retinoic acid can be oxidized to several metabolites by a panel of CYPs that differs for the different retinoic acid isomers. CYP26A1 is involved in the metabolic breakdown of retinoic acid by 4-hydroxylation. CYP26A1-mediated 4-hydroxylation is specific for all-trans-retinoic acid but not for the isomers 13-cis-retinoic acid and 9-cis-retinoic acid. CYP26C1 can also hydroxylate the trans form of retinoic acid it is unique in hydroxylating the 9-cis isomer of retinoic acid. CYP26B1 can also deactivate all-trans-retinoic acid by 4-hydroxylation. Another recently discovered cytochrome P450, called CYP2S1 is expressed in skin cells and is inducible by UV radiation, coal tar and all-trans retinoate. All trans retinoic acid also serves as a substrate for this enzyme. Phase II metabolism, mainly glucuronidation, is also observed for retinoic acid.