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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 维生素 B6 缺乏会导致细胞缺乏辅酶磷酸吡哆醛-PLP。 PLP 是单碳-1C 代谢阶段的辅酶，其中一个碳单位用于反应，包括核苷酸合成、从同型半胱氨酸-Hcy 再生蛋氨酸-蛋氨酸以及许多生物化合物的甲基化。 1C 代谢与转硫途径相关，在该途径中，Hcy 经历 PLP 依赖性分解代谢，产生半胱氨酸。 损害 1C 代谢的营养或遗传条件与血浆 Hcy 浓度升高和血管疾病风险增加有关。 据信，当氨基酸代谢的维生素 B6 依赖性途径经历最大的底物负荷时，维生素 B6 缺乏的代谢影响在蛋白质摄入后最为明显。 第一阶段将研究维生素 B6 营养对甘氨酸裂解系统依赖 PLP 生成 1C 单位以及谷胱甘肽合成的影响。 第二阶段将研究蛋氨酸代谢对维生素 B6 营养状况的依赖性。 每个阶段将涉及 14 名年轻人，他们将在大约 4 周的膳食维生素 B6 限制之前和之后使用静脉注射稳定同位素示踪剂进行代谢物分析和动力学分析。 受试者将被分配到第一阶段或第二阶段，除了使用的示踪剂和分析方法外，其设计相同。 我们假设维生素 B6 缺乏会导致餐后同型半胱氨酸再甲基化率、甘氨酸生成 1C 单位以及谷胱甘肽合成率降低。