Leo M A, Lieber C S
J Biol Chem. 1985 May 10;260(9):5228-31.
Rat liver microsomes were discovered to actively oxidize retinol to polar metabolites, including 4-hydroxyretinol, in a system requiring oxygen and NADPH. Involvement of cytochrome P-450 was indicated by CO and SKF-525A inhibition and reconstitution of this system with purified forms of cytochrome P-450 (b and f). Addition of excess unlabeled retinoic acid did not decrease the specific activity of the products formed from labeled retinol, suggesting that retinoic acid is not involved as an intermediate step. Microsomal inducers (such as phenobarbital) strikingly enhanced the activity of the system, resulting in 5-10-fold increased rates of retinol degradation. Furthermore, microsomal substrates (such as benzphetamine) inhibited microsomal retinol metabolism. This new pathway of retinol metabolism in liver microsomes may explain, at least in part, vitamin A-drug interactions, including drug-induced hepatic depletion of vitamin A.
在一个需要氧气和烟酰胺腺嘌呤二核苷酸磷酸（NADPH）的系统中，研究人员发现大鼠肝脏微粒体能将视黄醇（维生素A）积极氧化为极性代谢产物，包括4-羟基视黄醇。一氧化碳（CO）和SKF-525A的抑制作用以及用纯化形式的细胞色素P-450（b和f）对该系统进行重组，表明细胞色素P-450参与其中。添加过量的未标记视黄酸并没有降低由标记视黄醇形成的产物的比活性，这表明视黄酸不作为中间步骤参与其中。微粒体诱导剂（如苯巴比妥）显著增强了该系统的活性，导致视黄醇降解速率提高了5至10倍。此外，微粒体底物（如苄非他明）抑制了微粒体视黄醇代谢。肝脏微粒体中这种新的视黄醇代谢途径可能至少部分解释了维生素A与药物的相互作用，包括药物诱导的肝脏维生素A消耗。
