STEREOCHEMISTRY AND MECHANISMS OF ENZYME REACTION

立体化学和酶反应机制

• 批准号: 3289954
• 负责人: John M. Schwab
• 金额: $ 8.87万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-08-01 至 1986-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3289954
• 关键词: Clostridium; chemical hydration; enzyme induction /repression; hydrolase; hydroxyl group; stereochemistry

The study of two mechanistically cryptic enzyme-catalyzed dehydration reactions is proposed. An enzyme system from Clostridium aminobutyricum dehydrates 4-hydroxy butyryl CoA to E-2-butenoyl CoA, and another enzyme system, from Megasphera elsdenii, converts L-lactyl CoA to acrylyl CoA. These processes appear to involve the removal of relatively nonacidic protons, in contrast to the vast majority of enzyme-catalyzed dehydration reactions, in which the hydroxyl group and the proton which are eliminated are situated alpha- and beta-, respectively, to a carbanion-stabilizing functional group (esp. a carbonyl). These reactions will be studied by determining overall reaction stereochemistry, by observing the fates of fluorine-substituted substrates, by determining isotope effects, and by looking for partial exchanges involving protons and hydroxyl groups. These studies will require the synthesis of chirally labeled ethylene oxide, a potentially useful and hitherto unknown synthon. Elucidation of the mechanisms of these two dehydrations will help to define the structural and mechanistic requirements of enzyme-catalyzed dehydrations in general. Such information can be of great utility in predicting pathways of secondary metabolism as well as metabolism of foreign substances, including toxins and drugs.

两种机理隐蔽的酶催化脱水反应的研究 提出了反应。 氨基丁酸梭菌的酶系 将4-羟基丁酰辅酶A脱水为E-2-丁烯酰辅酶A，以及另一种酶 系统，将L-乳酰辅酶A转化为丙烯酰辅酶A。 这些过程似乎涉及去除相对非酸性的 质子，与绝大多数酶催化脱水相反， 反应，其中羟基和质子被消除， 分别位于碳负离子稳定剂的α-和β-位置， 官能团（特别是羰基）。 这些反应将通过以下方式进行研究： 确定整体反应立体化学，通过观察的命运 氟取代的底物，通过确定同位素效应， 寻找涉及质子和羟基的部分交换。 这些 研究将需要合成手性标记的环氧乙烷， 潜在有用的和迄今未知的合成子。 阐明 这两种脱水机制将有助于确定结构和 酶催化脱水的一般机械要求。 等 信息可以在预测继发性 代谢以及包括毒素在内的外来物质的代谢 还有毒品