KINETICS OF RETINOID METABOLISM BY ALCOHOL DEHYDROGENASE

乙醇脱氢酶的类视黄醇代谢动力学

• 批准号: 6168388
• 负责人: CAROL L STONE
• 金额: $ 2.82万
• 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 2000-09-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6168388
• 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），在胃肠道中产生 摄入β-胡萝卜素，在肝脏中被氧化成视黄醛。视网膜 对夜视很重要，维A酸及其产物 视网膜，对于细胞发育很重要。视黄醇、视黄醛和 类维生素A酸属于类维生素A的一类，类维生素A的水平为 与胎儿酒精综合症和夜盲症相关，影响 与酗酒有关。据推测，人类 胃和肝脏中的胞质乙醇脱氢酶同工酶 在类视黄醇代谢中充当生理酶，并且 摄入的乙醇会干扰这一过程。这两个目的的目的是—— 年探索性提案是为了确定使用的可行性 稳态、停流和快速扫描动力学以及计算机 模拟来检验这个假设。一组动力学数据将是 收集的描述了全反式维A酸的各个步骤和 肝脏和胃乙醇脱氢酶代谢 11-顺式-类视黄醇 37 摄氏度下的同工酶。在细胞中，类维生素A被运输 由一类称为细胞类视黄醇结合蛋白的结合蛋白 （CRBP）。 CRBP 以及乙醇和乙醛在 醇脱氢酶同工酶的类维生素A代谢也将被 评价。这些动力学数据将用于执行一系列 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的作用 肝脏中类视黄醇代谢中的乙醇脱氢酶同工酶 胃肠道，并将评估乙醇在胃肠道中的作用 这些酶对类维生素A代谢的干扰。