MECHANISTIC METALLOBIOCHEMISTRY OF COENZYME B

辅酶 B 的机械金属生物化学

• 批准号: 3227779
• 负责人: RICHARD G FINKE
• 金额: $ 11.55万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-07-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3227779
• 关键词: alkyl group; ammonia lyase; carbonates; chemical models; chemical reaction; chemical synthesis; diol; electrochemistry; erythrocytes; ethanolamines; isomer; metal complex; metal metabolism; metalloproteins; molecular biology; nuclear magnetic resonance spectroscopy; pernicious anemia; ribonucleotides; vitamin B12 coenzyme

The overall goal of this research is to understand, on a molecular level, the mechanism of the Adenosylcobalamin (Ado-B12 or Coenzyme B12)-dependent rearrangement reactions. A focal point of the research will be key cobalt-C5' bond homolysis of Ado-B12 and the steric, electronic, axial 5,6-dimethylbenzimidazole base, radical cage, and other factors influencing this crucial step of the enzymatic reactions. The B12 coenzyme is essential for the normal maturation of erythrocytes and, in man, insufficient amounts of B12 causes Pernicious Anemia. B12 is an essential cofactor in man for methylmalonyl-CoA mutase, an enzyme which catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA. Recent work indicates that there exists a family of functionally related and probably mechanistically similar enzymes that utilize a diiron (Fe2) rather than a B12 (Co) cofactor, noteably leucine-2,3-amino-mutase and the ribonucleotide reductases. These enzymes are widely distributed in humans, mammals, and plants. It appears, therefore, that a molecular understanding of the free radical chemistry and mechanism of action of the Ado-B12 -dependent reactions has a broader significance than was previously thought.

这项研究的总体目标是在分子水平上了解， 腺苷钴胺素（Adenosylbobalamin，简称B12或Coenzyme B12）依赖性 重排反应 研究的重点将是关键 钴-C5 '键的均裂和立体，电子，轴向 5，6-二甲基苯并咪唑碱、自由基笼等因素影响 这是酶促反应的关键步骤。 辅酶B12是红细胞正常成熟所必需的 在人类中，维生素B12不足会导致恶性贫血。 B12是 甲基丙二酰辅酶A β的人体必需辅因子，该酶 催化甲基丙二酰辅酶A异构化为琥珀酰辅酶A。 最近 工作表明，存在一个家庭的功能相关， 可能机制上类似的酶，利用二铁（Fe 2），而不是 比B12（Co）辅因子，特别是亮氨酸-2，3-氨基-亮氨酸和 核糖核苷酸还原酶 这些酶广泛分布在人体内， 哺乳动物和植物。 因此，从分子水平上理解 自由基化学和作用机制的研究 依赖性反应比以前认为的具有更广泛的意义。