SYNTHESIS OF VITAMIN B12 MODELS

维生素 B12 模型的合成

• 批准号: 3269791
• 负责人: PAUL DOWD
• 金额: $ 18.14万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-07-01 至 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3269791
• 关键词: biotransformation; catalyst; chemical models; chemical synthesis; cobalamin; enzyme complex; enzyme mechanism; glutamate decarboxylase; glutamates; isomerase; malonates; methylmalonyl coA epimerase; molecular cloning; nutrition related tag; stereochemistry; vitamin B12; vitamin B12 coenzyme

Vitamin B12, in the form of its coenzyme, is an obligatory cofactor in a series of twelve enzyme catalyzed reactions. The glutamate mutase, methyl- malonyl-CoA mutase and methylitaconate mutase enzymes are of outstanding interest because they catalyze carbon-skeleton rearrangements for which there have been no analogues in organic chemistry. The methylmalonyl-CoA to succinyl-CoA rearrangement is of crucial import in mammalian systems; it is the way the body converts propionate to succinate, leading into the main stream of biochemical metabolism. In this proposal, the mechanism by which these rearrangements occur will be explored using both model and enzymic systems. A new model for the methymalonyl-CoA system has been synthesized with an appended free radical trap to test for the occurrence of radical intermediates. This test will also be applied to the enzyme system. In addition, a new, synthetic malonate binding molecule will be used to study the reversibility of the model rearrangement. In order to facilitate the study of the function and structure of glutamate mutase, the gene will be cloned. Then, with adequate supplies of pure enzyme, mechanistic and structural studies will be initiated. Free radical and carbanion intermediates in the glutamate-methylaspartate rearrangement will be explored and a very successful Schiff base model will be developed. Surfactant-based models will be examined for their impact on our understanding of some unprecedented free radical migration reactions.

维生素B12，以辅酶的形式，是a的强制性辅助因子