KINETICS OF RETINOID METABOLISM BY ALCOHOL DEHYDROGENASE

乙醇脱氢酶的类维生素A代谢动力学

• 批准号: 2850417
• 负责人: CAROL L STONE
• 金额: $ 9.87万
• 依托单位: STEVENS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2850417
• 关键词: acetaldehyde; alcohol dehydrogenase; all trans retinol; chemical kinetics; computer simulation; data collection; detergents; enzyme mechanism; enzyme substrate complex; ethanol; isozymes; liver cells; liver metabolism; oxidation reduction reaction; oxidoreductase inhibitor; retinoid binding proteins; retinoids; stop flow technique; vitamin metabolism

Retinol (vitamin A), produced in the gastrointestinal tract after ingestion of beta-carotene, is oxidized to retinal in the liver. Retinal is important for night vision, and retinoid acid, and product of retinal, is important in cell development. Retinol, retinal, and retinoid acid are among a class of retinoids, and retinoid levels are correlated with fetal alcohol syndrome and night blindness, effects associated with alcoholism. It has been hypothesized that human cytosolic alcohol dehydrogenase isoenzymes in the stomach and liver function as physiological enzymes in retinoid metabolism, and that ingested ethanol interferes with this process. The purpose of this two- year exploratory proposal is to determine the feasibility of using steady-state, stopped-flow, and rapid scanning kinetics, and computer simulation to test this hypothesis. A set of kinetic data will be collected that describes the individual steps of all-trans-retinoid and 11-cis-retinoid metabolism by liver and gastric alcohol dehydrogenase isoenzymes at 37 degrees Celsius. In the cell, retinoids are transported by a class of binding proteins called cellular retinoid binding proteins (CRBP). The role of CRBP, as well as of ethanol and acetaldehyde, in retinoid metabolism by the alcohol dehydrogenase isozymes will also be evaluated. These kinetics data will be used to perform a series of computer-based simulation experiments that investigate the effect of enzyme, substrate, and product of retinoid metabolism. These experiments will contribute to efforts in identifying the role of human cytosolic alcohol dehydrogenase isoenzymes in retinoid metabolism in the liver and gastrointestinal tract, and will evaluate the role of ethanol in the perturbation of retinoid metabolism by these enzymes.

视黄醇（维生素A），产生于胃肠道后， 摄入β-胡萝卜素后，在肝脏中氧化为视网膜。视网膜 对夜视很重要，维甲酸， 视网膜，在细胞发育中很重要。视黄醇，视网膜，和 类维生素A酸是一类类维生素A， 与胎儿酒精综合征和夜盲症相关， 与酗酒有关。据推测，人类 胃和肝中的细胞溶质醇脱氢酶同工酶 在类维生素A代谢中起生理酶的作用， 摄入的乙醇会干扰这一过程。这两个目的- 一年的探索性建议是确定使用的可行性 稳态、停流和快速扫描动力学以及计算机 模拟来验证这个假设。一组动力学数据将被 收集描述全反式维甲酸的各个步骤， 肝和胃乙醇脱氢酶代谢11-顺式维甲酸 同工酶在37摄氏度。在细胞中，类维生素A 一种叫做细胞类维生素A结合蛋白的结合蛋白 （CRBP）. CRBP以及乙醇和乙醛在 通过乙醇脱氢酶同工酶的类维生素A代谢也将是 评估。这些动力学数据将用于进行一系列的 基于计算机的模拟实验，研究 类维生素A代谢的酶、底物和产物。这些实验 将有助于确定人类细胞质中的作用， 乙醇脱氢酶同工酶在类维生素A代谢的肝脏和 胃肠道，并将评估乙醇的作用， 这些酶对类维生素A代谢的干扰。