HYDROLYSIS OF VITAMIN A ESTERS IN LIVER

视黄酯的酶促水解是机体代谢的关键过程， 整体维生素A稳态。 虽然肝脏在心脏病中起着核心作用， 维生素A代谢，我们对肝酶的理解， 催化视黄酯的水解是不完全的。 仅一个这样 酶已被分离出来，纯的形式，中性，胆盐依赖性 视黄基酯水解酶（BSDREH），这只是最近才实现的。 这项建议的目的是获得关于下列方面的新的详细资料： 视黄醇酯的功能、调节和生理作用 肝脏中的水解酶。 这将提高对因素的基本理解 控制维生素A的体内平衡 这些信息很重要，因为 类维生素A在发育和维持中的关键作用 分化的组织和作用，维甲酸可能发挥预防 或治疗某些癌症。 在目标1中，肝脏BSDREH的比较 和胰胆固醇酯水解酶在蛋白质水平 结构、cDNA序列和酶特性， 检验肝脏和胰腺酶相同的假设 蛋白质或同种型。 在目标2中，肝BSDREH的调节将是 通过检验酶合成是在 翻译控制，酶活性受 翻译后的修饰 在目标3中，非胆盐依赖性视黄基 大鼠肝脏的酯水解酶将以纯的形式分离，用于详细描述 研究其生化和酶学性质。 In Aim 4肝癌 细胞培养模型系统将用于测试假设， 胆盐依赖性和胆盐非依赖性视黄酯水解酶发挥作用 在一个或多个肝脏维生素途径中的生理学重要作用 新陈代谢。

The enzymatic hydrolysis of retinyl esters is a key process in the body's overall vitamin A homeostasis. Although the liver plays a central role in vitamin A metabolism, our understanding of the hepatic enzymes that catalyse the hydrolysis of retinyl esters is incomplete. Only one such enzyme has been isolated in pure form, a neutral, bile salt dependent retinyl ester hydrolase (BSDREH), and this has only been recently achieved. The objective of this proposal is to obtain new and detailed information on the functions, regulation, and physiological role of the retinol ester hydrolases in the liver. This will improve basic understanding of factors controlling vitamin A homeostasis. Such information is important given the critical role of retinoids in the development and maintenance of differentiated tissues and the roles that retinoids may play in preventing or treating certain cancers. In Aim 1 comparisons of the hepatic BSDREH and pancreatic cholesteryl ester hydrolase at the levels of protein structure, CDNA sequence, and enzyme properties will be made in order to test the hypothesis that the hepatic and pancreatic enzymes are the same protein or isoforms. In Aim 2 the regulation of the hepatic BSDREH will be probed by testing the hypothesis that enzyme synthesis is under translational control and that enzyme activity is regulated by postranslational modifications. In Aim 3 the bile salt-independent retinyl ester hydrolases of rat liver will be isolated in pure form for detailed study of their biochemical and enzymological properties. In Aim 4 hepatoma cell culture model systems will be used to test the hypothesis that the bile salt dependent and bile salt-independent retinyl ester hydrolases play physiologically important roles in one or more pathways of hepatic vitamin A metabolism.