MICROSOMAL OXIDATION OF RETINOIC ACID IN HAMSTER LIVER, INTESTINE, AND TESTIS
MICROSOMAL OXIDATION OF RETINOIC ACID IN HAMSTER LIVER, INTESTINE, AND TESTIS
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仓鼠肝脏、肠和睾丸中视黄酸的微粒体氧化
DOI：
10.1111/j.1749-6632.1981.tb12736.x
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发表时间：
1981
影响因子：
5.2
通讯作者：
A. Roberts
中科院分区：
文献类型：
--
作者：
A. Roberts
正如 20 世纪 30 年代和 1940 年代预示着在建立水溶性 B 族维生素复合物的辅因子性质方面取得了突破一样，20 世纪 70 年代也大大增加了我们对脂溶性维生素的代谢和生化作用机制的了解。然而，与目前有关维生素 DZ 和 K 的代谢激活和生化目标的大量信息相比，3 我们对维生素 A 家族化合物成员的了解仍处于初级水平。视网膜在视觉周期中的作用已被明确定义，4但对于维生素的作用机制或维生素 A 在支持生长和上皮细胞分化中的更广泛功能所必需的特定代谢物知之甚少。任何旨在鉴定控制生长和上皮细胞分化所必需的维生素分子种类的研究的核心必须是视黄酸（RA）的生物化学研究。 RA 由视网膜不可逆地形成，已被确定为大鼠体内视黄醇的天然代谢物。6 然而，与视黄醇和视网膜不同，RA 不能储存并快速代谢。7这些特性及其支持维生素 A 缺乏动物生长的能力，10-12 促进体内上皮组织的分化“343 以及气管上皮 14 和鸡胚皮肤外植体 15 的分化”体外，并抑制体内和体外肿瘤的发展，16 人们对 RA 代谢的兴趣日益浓厚。在过去的三年中，方法学的进步，如更温和的提取程序 17 和高压液相色谱 [HPLC)1B,lg 已经导致从粪便 20 和尿液，z1，肠粘膜，2z 和肝脏中鉴定出 RA 的几种代谢物。 然而，仍然需要阐明这些代谢物形成的途径并确定哪些代谢物。最后，可能需要考虑代谢中的组织依赖性差异，特别是与其他组织相比，本报告总结了旨在解决这些与 RA 代谢相关的问题的实验。
Just as the 1930s and 1940s heralded breakthroughs in establishing the cofactor nature of the water-soluble B vitamin-complex,' so the 1970s have greatly increased our understanding of the metabolism and the biochemical mechanism of action of the fat-soluble vitamins. However, compared to the wealth of information now available regarding the metabolic activation and biochemical targets of vitamins DZ and K,3 our understanding of the members of the vitamin A family of compounds is still at an elementary level. The role of retinal in the visual cycle has been clearly defined,4 but little is known concerning the mechanisms of action of the vitamin or the specific metabolites necessary for the more generalized functions of vitamin A in the support of growth and epithelial cell differentiation. Central to any investigation aimed at the identification of the molecular species of the vitamin essential for the control of growth and epithelial cell differentiation must be a study of the biochemistry of retinoic acid (RA). Formed irreversibly from retina1,s RA has been identified as a natural metabolite of retinol in the rat.6 Unlike retinol and retinal, however, RA cannot be stored and is rapidly metabolized.7These properties, along with its ability to support the growth of vitamin A-deficient animals,l0-12 to promote differentiation of epithelial tissues in vivo"343 and of tracheal epithelium14 and chick embryo skin explants15 in vitro, and to suppress neoplastic development both in vivo and in vitro,16 have intensified interest in RA metabolism. In the last three years, methodological advances such as milder extraction procedures17 and high-pressure liquid chromatography [HPLC)lB,lg have resulted in the identification of several metabolites of RA from feces20 and urine,z1 from intestinal mucosa,2z and from liver.23 It remains, however, to elucidate the pathways involved in the formation of these metabolites and to identify which reactions, if any, lead to biochemical activation and which are of a catabolic nature. It is equally important to understand the controls operating on each of these pathways as well as their relationships to each other. Finally, tissue-dependent differences in the metabolism, particularly in epithelial target tissues as compared to other tissues, may need to be considered. This report summarizes experiments designed to address these issues concerning the metabolism of RA.