STRUCTURAL STUDIES ON COBALAMIN COMPLEXES

钴胺素复合物的结构研究

• 批准号: 8169968
• 负责人: CLYDE A SMITH
• 金额: $ 0.27万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169968
• 关键词: Animals; Biological; Blood; Cells; Clinical; Cobalamin; Complex; Computer Retrieval of Information on Scientific Projects Database; Corrinoids; Enzymes; Food; Funding; Grant; Human; Institution; Mammalian Cell; Megaloblastic Anemia; Metabolism; Nature; Neuropathy; Pernicious Anemia; Play; Reporting; Research; Research Personnel; Resources; Role; Sampling; Seaweed; Source; Structure; Tissues; United States National Institutes of Health; aquacobalamin; cobamamide; glutathionylcobalamin; microbial; nitritocobalamin; nitrosocobalamin; sulfitocobalamin

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Corrinoid-dependent enzymes are widespread in nature and play key roles in human, animal and microbial metabolism. The clinical hallmarks of B12 deficiency are megaloblastic anemia (?pernicious anemia?), and neuropathies. Upon reaching cells, cobalamin derivatives are converted to MeCbl and AdoCbl by currently ill-defined mechanisms. Many studies have been carried out over the past several decades involving the extraction and identification of cobalamins from mammalian cells, tissue and blood, in addition to other biological samples such as foods and seaweed. Adenosylcobalamin, methylcobalamin and aquacobalamin are the major cobalamin metabolites isolated from biological samples but there are also reports of the isolation of nitrocobalamin and sulfitocobalamin from biological sources, along with other unknown complexes. We have synthesized a number of cobalamin derivatives to assist in the identification of unknown cobalamins isolated from biological samples, and we have determined the crystal structures of a number of these complexes, including N-acetylcysteinylcobalamin and nitrosocobalamin. The structures of two alkylcobalamins, ethylcobalamin and butylcobalamin have also been determined and recently reported. Further studies on other biologically-relevent cobalamin complexes are underway, including glutathionylcobalamin which has for many years evaded all attempts at structure determination.

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