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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 维生素B6缺乏导致辅酶磷酸吡哆醛-PLP的细胞缺乏。 PLP是一种辅酶，处于一个碳-1C代谢阶段-一个碳单元用于包括核苷酸合成、从同型半胱氨酸-Hcy再生甲硫氨酸- Met和许多生物化合物甲基化的反应的阵列。 1C代谢与转硫途径有关，其中同型半胱氨酸经历PLP依赖性分解代谢，产生半胱氨酸。 影响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相关。 据信，当氨基酸代谢的维生素B6依赖性途径经历最大底物负荷时，维生素B6缺乏的代谢影响在蛋白质摄入后将最明显。 第1阶段将研究维生素B6营养对通过甘氨酸裂解系统产生的1C单位的PLP依赖性产生以及对谷胱甘肽合成的影响。 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。 每个阶段将涉及14名年轻人，他们将在饮食维生素B6限制约4周之前和之后使用静脉输注的稳定同位素示踪剂进行代谢物分析和动力学分析。 受试者将被分配至I期或II期，除所用的示踪剂和分析方法外，其设计相同。 我们推测，维生素B6缺乏会导致餐后同型半胱氨酸再甲基化率降低，甘氨酸产生1C单位，谷胱甘肽合成。