Napoli J L, Race K R
Arch Biochem Biophys. 1987 May 15;255(1):95-101. doi: 10.1016/0003-9861(87)90298-0.
This report shows that a spectrum of vitamin A-dependent tissues can produce retinoic acid by synthesis in situ, indicates that cellular retinol and retinoic acid binding proteins are not obligatory to retinoic acid synthesis, and provides initial characterization of retinoic acid synthesis by rat tissues. Retinoic acid synthesis from retinol was detected in homogenates of rat testes, liver, lung, kidney, and small intestinal mucosa, but not spleen. Zinc did not stimulate the conversion of retinol into retinoic acid by liver homogenates. Retinoic acid synthesis was localized in cytosol of liver and kidney, where its rate of synthesis from retinol was fourfold (liver) and sevenfold (kidney) slower than from retinal. The synthesis of retinoic acid from retinol required NAD and was not supported by NADP. NADH (0.5 mM) reduced retinoic acid synthesis from retinol, supported by NAD (2 mM), by 50-70%, but was fivefold less potent in reducing retinoic acid synthesis from retinal. Dithiothreitol enhanced the conversion of retinol, but not retinal, into retinoic acid. EDTA inhibited the conversion of retinol into retinoic acid slightly (13%, liver; 29%, kidney). A high ethanol concentration (100 mM), relative to retinoid substrate (10 microM), inhibited retinoic acid synthesis from retinol (liver, 54%; kidney, 30%) and from retinal (30%, liver; 9%, kidney). 4'-(9-Acridinylamino)methansulfon-m-anisidine, an inhibitor of aldehyde oxidase, and disulfiram, a sulfhydryl-group crosslinking agent, were potent inhibitors of retinoic acid synthesis at 10 microM or less, and seemed equipotent in liver and kidney. 4-Methylpyrazole, an inhibitor of ethanol metabolism, also inhibited retinoic acid synthesis from retinol, but was less potent than the former two inhibitors, and affected liver to a greater extent than kidney, particularly with retinal as substrate.
本报告表明，一系列依赖维生素A的组织可通过原位合成产生视黄酸，指出细胞视黄醇和视黄酸结合蛋白对视黄酸合成并非必不可少，并提供了大鼠组织视黄酸合成的初步特征。在大鼠睾丸、肝脏、肺、肾脏和小肠黏膜的匀浆中检测到了视黄醇向视黄酸的转化，但在脾脏中未检测到。锌并未刺激肝脏匀浆将视黄醇转化为视黄酸。视黄酸合成定位于肝脏和肾脏的胞质溶胶中，在其中视黄醇合成视黄酸的速率比视黄醛慢四倍（肝脏）和七倍（肾脏）。视黄醇合成视黄酸需要NAD，NADP不能支持该反应。NADH（0.5 mM）在NAD（2 mM）存在的情况下，使视黄醇合成视黄酸的反应降低50 - 70%，但在降低视黄醛合成视黄酸的反应方面效力低五倍。二硫苏糖醇增强了视黄醇而非视黄醛向视黄酸的转化。EDTA对视黄醇转化为视黄酸有轻微抑制作用（肝脏中为13%；肾脏中为29%）。相对于类维生素A底物（10 microM），高乙醇浓度（100 mM）抑制视黄醇合成视黄酸（肝脏中为54%；肾脏中为30%）以及视黄醛合成视黄酸（肝脏中为30%；肾脏中为9%）。4'-（吖啶-9-基氨基）甲磺酰间茴香胺，一种醛氧化酶抑制剂，以及双硫仑，一种巯基交联剂，在浓度为10 microM或更低时是视黄酸合成的有效抑制剂，在肝脏和肾脏中似乎效力相当。4-甲基吡唑，一种乙醇代谢抑制剂，也抑制视黄醇合成视黄酸，但效力不如前两种抑制剂，并且对肝脏的影响比对肾脏更大，尤其是以视黄醛作为底物时。
