视黄酸代谢生成5,6-环氧视黄酸、视黄酰-β-葡萄糖醛酸苷及其他极性代谢产物。

The metabolism of retinoic acid to 5,6-epoxyretinoic acid, retinoyl-beta-glucuronide, and other polar metabolites.

作者信息

DeLuca H F, Zile M, Sietsema W K

出版信息

Ann N Y Acad Sci. 1981 Feb 27;359:25-36. doi: 10.1111/j.1749-6632.1981.tb12734.x.

DOI:10.1111/j.1749-6632.1981.tb12734.x

Abstract

A description of the enzyme that produces 5,6-epoxyretinoic acid from all-trans-retinoic acid has been presented. This enzyme system is found in highest concentrations in the kidney followed by intestine, liver and spleen. The enzyme requires molecular oxygen, magnesium ions, ATP, and NADPH. In the kidney, it is found in the mitochondrial and microsomal fractions and has a Michaelis constant of 3.2 X 10(-6) M and 3.7 X 10(-6) M for 13-cis and all-trans-retinoic acid, respectively. The resultant product, 5,6-epoxyretinoic acid, has minimal activity in supporting growth of vitamin A-deficient rats, its activity estimated to be 0.5% that of retinoic acid. An investigation of the biliary excretion products of tritiated retinoic acid has revealed several unknown metabolites. A glucuronidase sensitive metabolite from these products has been isolated and identified as retinoyl-beta-glucuronide by ultraviolet absorption spectrometry and mass spectrometry. The retinoyl-beta-glucuronide originally discovered by Olson and collaborators accounts for only 12% of the total excreted biliary products of retinoic acid. At least four to six major unknown retinoic acid metabolites, in addition to retinoyl-beta-glucuronide, have been detected and will shortly be identified.

摘要

已有关于从全反式视黄酸生成5,6 -环氧视黄酸的酶的描述。该酶系统在肾脏中浓度最高，其次是肠道、肝脏和脾脏。该酶需要分子氧、镁离子、ATP和NADPH。在肾脏中，它存在于线粒体和微粒体部分，对13 -顺式和全反式视黄酸的米氏常数分别为3.2×10⁻⁶ M和3.7×10⁻⁶ M。生成的产物5,6 -环氧视黄酸在支持维生素A缺乏大鼠生长方面活性极小，其活性估计为视黄酸的0.5%。对氚标记视黄酸的胆汁排泄产物的研究揭示了几种未知代谢物。已从这些产物中分离出一种对葡糖醛酸酶敏感的代谢物，并通过紫外吸收光谱法和质谱法鉴定为视黄酰-β-葡糖醛酸。最初由奥尔森及其合作者发现的视黄酰-β-葡糖醛酸仅占视黄酸总胆汁排泄产物的12%。除了视黄酰-β-葡糖醛酸外，至少还检测到四到六种主要的未知视黄酸代谢物，不久将对其进行鉴定。