VITAMIN B6 DEPENDENCE OF ONE-CARBON METABOLISM

维生素 B6 对一碳代谢的依赖性

• 批准号: 7717104
• 负责人: JESSE F. GREGORY
• 金额: $ 7.59万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7717104
• 关键词: Affect; Amino Acid Metabolism Pathway; Antioxidants; Biological; Carbon; Catabolism; Coenzymes; Computer Retrieval of Information on Scientific Projects Database; Condition; Cysteine; Dependence; Elevation; Folch-Pi apoprotein; Funding; Generations; Genetic; Glutathione; Grant; Hereditary Disease; Homocysteine; Homocystine; Human; Institution; Intake; Link; Metabolic; Metabolism; Methionine; Methionine Metabolism Pathway; Methylation; Myelin Proteolipid Protein; Natural regeneration; Nutritional; Nutritional status; Pathway interactions; Phase; Plasma; Proteins; Protocols documentation; Pyridoxal Phosphate; Reaction; Recycling; Research; Research Personnel; Resources; Risk; Source; United States National Institutes of Health; Vascular Diseases; Vitamin B 6 Deficiency; Vitamin B6; experience; glycine cleavage system; human subject; nucleotide metabolism; nutrition

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. Marginal vitamin B6 deficiency, which occurs commonly worldwide, leads to a cellular deficiency of the coenzyme pyridoxal phosphate. PLP is a coenzyme in several phases of one carbon metabolism 1C, which is the array of reactions in which one carbon units are acquired and used in reactions including nucleotide synthesis, regeneration of methionine from homocysteine, and methylation of many biological compounds. 1C metabolism is linked to the transsulfuration pathway in which Hcy undergoes PLP-dependent catabolism leading to cysteine, whose availability governs the formation of the antioxidant glutathione. 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. The human subjects protocols of this study consist of two distinct phases intended to extend our understanding of basic human 1C metabolism and the effects of marginal vitamin B6 deficiency under postprandial conditions. 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, with particular emphasis on the recycling of Hcy to Met. The results of this study will aid in assessing the consequences of nutritional and genetic variables affecting human metabolism.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 世界各地普遍存在的边际维生素B6缺乏症会导致辅酶磷酸吡哆醛的细胞缺乏症。PLP是一个碳代谢1C的几个阶段的辅酶，是获得一个碳单位并用于核苷酸合成、同型半胱氨酸再生蛋氨酸和许多生物化合物甲基化的一系列反应。1C代谢与跨硫途径有关，在该途径中，Hcy经历PLP依赖的分解代谢，导致半胱氨酸，半胱氨酸的可获得性控制抗氧化剂谷胱甘肽的形成。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。人们认为，当依赖维生素B6的氨基酸代谢途径经历最大底物负荷时，维生素B6缺乏对代谢的影响将在蛋白质摄入后最为明显。这项研究的人类受试者方案包括两个不同的阶段，旨在扩大我们对基本的人类1C代谢和餐后条件下边际维生素B6缺乏的影响的理解。第一阶段将研究维生素B6营养对依赖PLP的甘氨酸裂解系统产生1C单位的影响以及对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营养状态的依赖，特别强调同型半胱氨酸到蛋氨酸的循环。这项研究的结果将有助于评估影响人类新陈代谢的营养和遗传变量的后果。