VITAMIN B6 DEPENDENCE OF ONE-CARBON METABOLISM: GLYCINE CLEAVAGE ASSESSMENT

维生素 B6 对一碳代谢的依赖性：甘氨酸裂解评估

• 批准号: 7717141
• 负责人: JESSE F. GREGORY
• 金额: $ 1.95万
• 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/7717141
• 关键词: Amino Acids; Antioxidants; Biological; Carbon; Carbon Dioxide; Catabolism; Cleaved cell; Computer Retrieval of Information on Scientific Projects Database; Cysteine; Decarboxylation; Dependence; Diet; Disease; Equilibrium; Female; Funding; Glutathione; Glycine; Grant; Hereditary Disease; Homocysteine; Homocystine; Human; Infusion procedures; Institution; Investigation; Kinetics; Label; Link; Metabolic; Metabolism; Methionine; Methylation; Mitochondria; Natural regeneration; Nutrient; Nutritional; Pathway interactions; Pattern; Plasma; Protein Biosynthesis; Rate; Reaction; Research; Research Personnel; Resources; Risk; Role; Source; Tracer; United States National Institutes of Health; Vascular Diseases; Vitamin B6; glycine cleavage system; male; nucleotide metabolism; nutrition; purine metabolism; 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. Amino acid glycine has multiple roles in human metabolism, in protein synthesis, one-carbon metabolism, purine synthesis, and component of glutathione. Through mitochondrial glycine cleavage system glycine is cleaved to CO2, NH3, and a 1C-unit in the form of 5,10-methylenetetrahydrofolate 5,10-CH2-THF. This unit from glycine is used in reactions of nucleotide synthesis, regeneration of methionine from homocysteine, and methylation of biological compounds. 1C metabolism is linked to transsulfuration pathway in which homocysteine undergoes vitamin B6 dependent catabolism leading to cysteine, whose availability governs formation of antioxidant glutathione. Nutritional or genetic conditions impairing 1C metabolism are associated with elevated plasma homocysteine concentration and increased risk of vascular disease. We will evaluate glycine metabolism using a single-labeled glycine. 6 healthy, nutritionally adequate, young adults,3 male, 3 female will undergo metabolite profiling and kinetic analysis using intravenously infused stable isotopic tracers performed after 2d of controlled, nutrient-balanced diet. We hypothesize that the rate of breath 13CO2 enrichment will be lower after infusion of [1-13C1]glycine compared to observed rate after infusion with [1,2-13C2]glycine. Results will aid assessing rate and pattern of glycine decarboxylation and metabolic products supporting investigations on relationships between glycine, vitamin B6 nutrition and disease.

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。子项目及 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。 氨基酸甘氨酸在人体新陈代谢、蛋白质合成、一碳代谢、嘌呤合成以及谷胱甘肽的成分中具有多种作用。 通过线粒体甘氨酸裂解系统，甘氨酸被裂解为 CO2、NH3 和 5,10-亚甲基四氢叶酸 5,10-CH2-THF 形式的 1C 单元。 该甘氨酸单元用于核苷酸合成、从同型半胱氨酸再生甲硫氨酸以及生物化合物甲基化的反应。 1C 代谢与转硫途径相关，其中同型半胱氨酸经历维生素 B6 依赖性分解代谢，产生半胱氨酸，半胱氨酸的可用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同型半胱氨酸浓度升高和血管疾病风险增加有关。 我们将使用单标记甘氨酸评估甘氨酸代谢。 6 名健康、营养充足的年轻人（3 名男性、3 名女性）将在 2 天受控营养均衡饮食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。 我们假设，与输注 [1,2-13C2] 甘氨酸后观察到的速率相比，输注 [1-13C1] 甘氨酸后呼吸 13CO2 富集率会更低。 结果将有助于评估甘氨酸脱羧和代谢产物的速率和模式，支持甘氨酸、维生素 B6 营养与疾病之间关系的研究。