HEMOGLOBIN, MYOGLOBIN, ALCOHOL, AND HEART DISEASE

血红蛋白、肌红蛋白、酒精和心脏病

• 批准号: 3438681
• 负责人: WILLIAM H FUCHSMAN
• 金额: $ 5.5万
• 依托单位: OBERLIN COLLEGE
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1990-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3438681
• 关键词: acetaldehyde; catalyst; enzyme mechanism; ethanol; heart disorder; heme; hemoglobin; hydroxylation; methanol; methylation; myoglobin; oligopeptides; oxidation

The project's long-term objectives are an understanding of the in vivo significance and the mechanisms of hemoglobin- and myoglobin-catalyzed monooxygenase-like reactions. One specific aim is to determine by in vitro studies whether hemoglobin and myoglobin catalyze or otherwise participate in monooxygenase- like alcohol oxidations; the results, if positive, might have a direct bearing on the physiological mechanism for ethanol abuse- induced heart disease. A second specific aim is to determine whether protein participation in catalysis is the reason that hemoglobin shows two different kinetic constants (KM's) for monooxygenase-like ring hydroxylation and demethylation of the same substance N-methyl aniline. The first aim will be accomplished by in vitro catalysis assays involving hemoglobin or myoglobin and ethanol or methanal under monooxygenase conditions. A nonenzymatic spectrophotometric assay for acetaldehyde (the product of ethanol oxidation) will be refined for use in the assays. Both extent of reaction and also the degree to which the hemoglobin or myoglobin survives the reaction unchanged will be determined. The second aim will be accomplished by in vitro kinetics experiments involving N-methyl aniline oxidation under monooxygenase conditions. Myoglobin will be used as a single-site catalyst, and heme oligopeptides and water-soluble hemes will be used as catalysts that possess either minimal or no protein components. The results will be compared with the results from hemoglobin-catalyzed reactions.

该项目的长期目标是了解 体内意义和机制的血红蛋白和 肌红蛋白催化的单加氧酶样反应。 一个具体 目的是通过体外研究确定血红蛋白和 肌红蛋白催化或参与单加氧酶- 像酒精氧化;结果，如果阳性，可能有一个 直接关系到酒精滥用的生理机制- 诱发心脏病。 第二个具体目标是确定 蛋白质参与催化是否是 血红蛋白显示两个不同的动力学常数（KM）， 单加氧酶样环的羟基化和去甲基化 相同物质N-甲基苯胺。 第一个目标将通过体外催化测定来实现 涉及血红蛋白或肌红蛋白和乙醇或甲醛， 单加氧酶条件。 非酶分光光度法 乙醛（乙醇氧化的产物）的测定将 精制以用于测定。 反应的程度以及 血红蛋白或肌红蛋白存活的程度 将确定反应不变。 第二个目标将通过体外动力学来实现 涉及N-甲基苯胺氧化的实验， 单加氧酶条件。 肌红蛋白将用作单部位 催化剂，血红素寡肽和水溶性血红素将是 用作催化剂，具有最少或没有蛋白质 件. 结果将与来自 血红蛋白催化反应。