Vitamin B6 dependence of one-carbon metabolism quantified in human subjects

单碳单元的获取和转移在DNA、神经递质和神经系统膜的合成中具有重要意义。甘氨酸、丝氨酸和蛋氨酸作为单碳单位的供体或受体是单碳代谢的主要参与者。以吡哆醛-5 ' -磷酸形式存在的维生素B6是一种辅酶，参与多种单碳代谢反应，包括甘氨酸和丝氨酸释放一碳单位。边缘性维生素B6缺乏症在世界范围内很常见，并与冠状动脉疾病、中风和阿尔茨海默病的风险增加有关；然而，对其生理后果的描述却很少。利用稳定同位素示踪剂，本研究旨在量化甘氨酸、丝氨酸和蛋氨酸的餐后动力学以及它们的动力学对维生素B6状态的依赖。使用甘氨酸示踪剂的两种输注方案已被用于测定健康男性和女性体内甘氨酸周转率、甘氨酸基单碳单位的生成以及抗氧化剂谷胱甘肽的合成。第三种人体示踪剂输注方案将确定维生素B6缺乏对蛋氨酸循环动力学、蛋氨酸再生/再甲基化和转硫途径的影响。所有动力学研究的结果将有助于产生关于人类单碳代谢的新知识，并有助于更好地了解维生素B6状态对相关疾病的影响。

The acquisition and transfer of one-carbon units is of major relevance in the synthesis of DNA, neurotransmitters, and membranes of the nervous system. The amino acids glycine, serine, and methionine are major participants in one-carbon metabolism either as donor or acceptor of onecarbon units. Vitamin B6 in form of pyridoxal-5’-phosphate is a coenzyme in multiple reactions of the one-carbon metabolism including the release of one-carbon units from glycine and serine. Marginal vitamin B6 deficiency is common world-wide and has been associated with increased risk of coronary artery disease, stroke, and Alzheimer’s Disease; however, its physiological consequences have been poorly characterized. With the use of stable isotope tracers, the research aims to quantify postprandial kinetics of glycine, serine, and methionine and the dependence of their kinetics on vitamin B6 status. Two infusion protocols using glycine tracers have been performed for determination of the rates of in vivo glycine turnover, glycine-based generation of one-carbon units, and the synthesis of the antioxidant glutathione in healthy men and women. A third human tracer infusion protocol will determine the effect of vitamin B6 deficiency on the kinetics of the methionine cycle, the regeneration/remethylation of methionine and the transsulfuration pathway. The results of all kinetic studies will aid in generating new knowledge of human one-carbon metabolism and in better understanding the impact of vitamin B6 status on related diseases.