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。 氨基酸甘氨酸在人类代谢，蛋白质合成，单碳代谢，嘌呤合成和谷胱甘肽的成分中具有多个作用。 通过线粒体甘氨酸裂解系统甘氨酸以5,10-10-甲基乙四氢叶酸盐为5,10-CH2-THF的形式裂解至CO2，NH3和1C单位。 该单元来自甘氨酸，用于核苷酸合成的反应，同型半胱氨酸的蛋氨酸再生以及生物化合物的甲基化。 1C代谢与透明度途径有关，其中同型半胱氨酸经历了维生素B6依赖性的分解代谢，导致半胱氨酸的可用性控制抗氧化剂谷胱甘肽的形成。 营养或遗传状况损害1C代谢与血浆同型半胱氨酸浓度升高和血管疾病风险增加有关。 我们将使用单标记的甘氨酸评估甘氨酸代谢。 6健康，营养充足的年轻人，3名男性，3位女性将使用静脉注入的稳定同位素示踪剂进行代谢物谱分析和动力学分析，在2D受控的，营养平衡的饮食后进行。 我们假设在输注[1-13c1]甘氨酸后，与[1,2-13C2]甘氨酸输注的速率相比，输注[1-13C1]甘氨酸后的呼气速率将较低。 结果将有助于评估甘氨酸脱羧的速率和模式，并支持对甘氨酸，维生素B6营养与疾病之间关系的研究。