Kedishvili N Y, Gough W H, Davis W I, Parsons S, Li T K, Bosron W F
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, 46202-5122, USA.
Biochem Biophys Res Commun. 1998 Aug 10;249(1):191-6. doi: 10.1006/bbrc.1998.9105.
All-trans retinoic acid (atRA) is a powerful morphogen synthesized in a variety of tissues. Oxidation of all-trans retinol to all-trans retinal determines the overall rate of atRA biosynthesis. This reaction is catalyzed by multiple dehydrogenases in vitro. In the cells, most all-trans retinol is bound to cellular retinol binding protein (CRBP). Whether retinoic acid is produced from the free or CRBP-bound retinol in vivo is not known. The current study investigated whether human medium-chain alcohol/retinol dehydrogenases (ADH) can oxidize the CRBP-bound retinol. The results of this study suggest that retinol bound to CRBP cannot be channeled to the active site of ADH. Thus, the contribution of ADH isozymes to retinoic acid biosynthesis will depend on the amount of free retinol in each cell. Physiological levels of ethanol will substantially inhibit the oxidation of free retinol by human ADHs: class I, alpha alpha and beta 2 beta 2; class II, pi pi; and class IV, sigma sigma.
全反式维甲酸（atRA）是在多种组织中合成的一种强大的形态发生素。全反式视黄醇氧化为全反式视黄醛决定了atRA生物合成的总体速率。该反应在体外由多种脱氢酶催化。在细胞中，大多数全反式视黄醇与细胞视黄醇结合蛋白（CRBP）结合。体内视黄酸是由游离视黄醇还是与CRBP结合的视黄醇产生尚不清楚。当前研究调查了人类中链醇/视黄醇脱氢酶（ADH）是否能氧化与CRBP结合的视黄醇。这项研究的结果表明，与CRBP结合的视黄醇无法被输送到ADH的活性位点。因此，ADH同工酶对视黄酸生物合成的贡献将取决于每个细胞中游离视黄醇的量。生理水平的乙醇会显著抑制人类ADH对游离视黄醇的氧化：I类，αα和β2β2；II类，ππ；以及IV类，σσ。
