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

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。 氨基酸甘氨酸在人体代谢、蛋白质合成、一碳代谢、嘌呤合成和谷胱甘肽组分中具有多种作用。 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-CH 2-THF形式的1C单元。 这个单位来自甘氨酸，用于核苷酸合成反应，从同型半胱氨酸中再生甲硫氨酸，以及生物化合物的甲基化。 1C代谢与转硫途径有关，其中同型半胱氨酸经历维生素B6依赖性催化作用，导致半胱氨酸，其可用性控制抗氧化剂谷胱甘肽的形成。 影响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价甘氨酸代谢。6名健康、营养充足的年轻成年人（3名男性，3名女性）将在2天的受控、营养平衡饮食后使用静脉输注的稳定同位素示踪剂进行代谢物谱分析和动力学分析。 我们假设输注[1- 13 C1]甘氨酸后呼吸13 CO2富集率低于输注[1，2 - 13 C2]甘氨酸后观察到的速率。 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营养和疾病之间关系的调查。

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.