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; 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 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.在过去的几十年中，已经进行了许多研究，涉及从哺乳动物细胞，组织和血液中提取和鉴定其他生物样品（例如食品和海藻）。腺苷泡剂，甲基生醛酰胺和紫杉醇是从生物样品中分离出来的主要钴胺素代谢物，但也有报道称，硝酸核盐和磺基番胺从生物学来源分离出来，以及其他不知名的复合物。 我们已经合成了许多钴胺衍生物，以帮助鉴定从生物样品中分离出的未知钴胺素，并且我们确定了许多这些复合物的晶体结构，包括N-乙酰基脊酯蛋白酶白细胞素和硝基核核素。 The structures of two alkylcobalamins, ethylcobalamin and butylcobalamin have also been determined and recently reported. 对其他生物学上相关的钴胺素复合物的进一步研究正在进行中，包括多年来逃避所有结构测定尝试的谷胱甘肽核酸盐。