STEREOCHEMISTRY AND MECHANISMS OF ENZYME REACTION

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

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.