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

一碳单元的获得和转移与DNA、神经递质和神经系统膜的合成有重要关系。氨基酸甘氨酸、丝氨酸和甲硫氨酸作为一个碳单位的供体或受体是一个碳代谢的主要参与者。维生素B6以吡哆醛-5 '-磷酸盐的形式存在，是单碳代谢的多个反应中的辅酶，包括从甘氨酸和丝氨酸释放一碳单元。边际维生素B6缺乏症在世界范围内很常见，并且与冠状动脉疾病、中风和阿尔茨海默病的风险增加有关;然而，其生理后果的特征很差。通过使用稳定同位素示踪剂，该研究旨在量化甘氨酸，丝氨酸和蛋氨酸的餐后动力学及其动力学对维生素B6状态的依赖性。两个输注协议，使用甘氨酸示踪剂已进行测定的速率在体内甘氨酸营业额，甘氨酸为基础的一代的一碳单位，和合成的抗氧化剂谷胱甘肽在健康的男性和女性。第三种人体示踪剂输注方案将确定维生素B6缺乏对甲硫氨酸循环动力学、甲硫氨酸再生/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人类一碳代谢的新知识，并更好地了解维生素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.