VITAMIN B6 DEPENDENCE OF ONE-CARBON METABOLISM

维生素 B6 对一碳代谢的依赖性

• 批准号: 7950722
• 负责人: JESSE F. GREGORY
• 金额: $ 2.14万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7950722
• 关键词: Amino Acid Metabolism Pathway; Biological; Carbon; Catabolism; Clinical Research; Coenzymes; Computer Retrieval of Information on Scientific Projects Database; Cysteine; Dependence; Funding; Generations; Glutathione; Glycine; Grant; Hereditary Disease; Homocysteine; Homocystine; Institution; Intake; Kinetics; Link; Metabolic; Metabolism; Methionine; Methionine Metabolism Pathway; Methylation; Natural regeneration; Nutritional; Nutritional status; Pathway interactions; Phase; Plasma; Proteins; Pyridoxal Phosphate; Reaction; Research; Research Personnel; Resources; Risk; Source; Tracer; United States National Institutes of Health; Vascular Diseases; Vitamin B 6 Deficiency; Vitamin B6; analytical method; design; experience; glycine cleavage system; meetings; nucleotide metabolism; nutrition; young adult

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. Vitamin B6 deficiency leads to a cellular deficiency of the coenzyme pyridoxal phosphate-PLP. PLP is a coenzyme in phases of one carbon-1C metabolism - the array in which one carbon units are used in reactions including nucleotide synthesis, regeneration of methionine- Met from homocysteine-Hcy, and methylation of many biological compounds. 1C metabolism is linked to the transsulfuration pathway in which Hcy undergoes PLP-dependent catabolism leading to cysteine. Nutritional or genetic conditions that impair 1C metabolism are associated with elevation in plasma Hcy concentration and increased risk of vascular disease. It is believed that the metabolic effects of vitamin B6 deficiency will be most pronounced following protein intake when the vitamin B6-dependent pathways of amino acid metabolism experience the greatest substrate load. Phase 1 will investigate the effects of vitamin B6 nutrition on the PLP-dependent generation of 1C units by the glycine cleavage system and on the synthesis of glutathione. Phase 2 will investigate the dependence of methionine metabolism on vitamin B6 nutritional status. Each phase will involve 14 young adults, who will undergo metabolite profiling and kinetic analysis using intravenously infused stable isotopic tracers performed before and after a ~4-week period of dietary vitamin B6 restriction. Subjects will be assigned to either Phase 1 or Phase 2, which will be identical in design except for the tracers and analytical methods used. We hypothesize that vitamin B6 deficiency will yield reduction in postprandial rates of homocysteine remethylation, generation of 1C units from glycine, and synthesis of glutathione.

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。 维生素B6缺乏会导致辅酶吡啶毒素磷酸-PLP的细胞缺乏。 PLP是一种碳-1C代谢的阶段的辅酶 - 在包括核苷酸合成，同型半胱氨酸-HCY中蛋氨酸的再生以及许多生物学化合物的甲基化中，将一个碳单元用于反应。 1C代谢与HCY经历PLP依赖性分解代谢的转硫途径有关。 损害1C代谢的营养或遗传条件与血浆HCY浓度的升高和血管疾病风险增加有关。 人们认为，当蛋白质摄入蛋白摄入后，维生素B6缺乏症的代谢作用将最为明显，当时氨基酸代谢的维生素B6依赖性途径经历了最大的底物负荷。 阶段1将研究维生素B6营养对甘氨酸裂解系统和谷胱甘肽的合成的影响对PLP依赖性1C单位的影响。 第2阶段将研究蛋氨酸代谢对维生素B6营养状况的依赖性。 每个阶段都将涉及14名年轻人，他们将使用静脉注入稳定的同位素示踪剂进行代谢物分析和动力学分析，该饮食中和之后进行了约4周的饮食维生素B6限制。 受试者将被分配给第1阶段或第2阶段，除了所使用的示踪剂和分析方法外，该受试者在设计中将是相同的。 我们假设维生素B6缺乏症会降低餐后同型半胱氨酸外甲基化的速率，甘氨酸产生的1C单位以及谷胱甘肽的合成。