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

人类受试者一碳代谢维生素 B6 依赖性的量化

• 批准号: 61580964
• 负责人: Dr. Katja Yvonne Lamers
• 金额: --
• 依托单位: Food Science and Human Nutrition Department
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/61580964?language=en
• 关键词: Vitamin; B6; dependence; carbon; metabolism

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.

一碳单位的获取和转移在DNA、神经递质和神经系统膜的合成中具有重要意义。甘氨酸、丝氨酸和蛋氨酸是一碳代谢的主要参与者，无论是作为一碳单位的供体还是受体。维生素B6以吡哆醛-5‘-磷酸形式存在，是一碳代谢的多种反应中的辅酶，包括从甘氨酸和丝氨酸释放一碳单位。边际维生素B6缺乏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，其生理后果的特征很差。通过使用稳定的同位素示踪剂，这项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经被用于确定健康男性和女性体内甘氨酸周转率、基于甘氨酸的一碳单位的生成以及抗氧化剂谷胱甘肽的合成。第三个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/再甲基化和硫磺转化途径的影响。所有动力学研究的结果将有助于产生关于人类一碳代谢的新知识，并有助于更好地了解维生素B6状态对相关疾病的影响。