Nutritional regulation of homocysteine metabolism

同型半胱氨酸代谢的营养调节

• 批准号: 217448-2009
• 负责人: House, James
• 金额: $ 3.21万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=514204
• 关键词: Nutritional; regulation; homocysteine; metabolism

The sulphur amino acid methionine plays critical roles in animal cells as a substrate for protein synthesis (structural, enzymes, hormones), as a methyl donor (neurotransmitter synthesis, DNA stability), and for the synthesis of the amino acid cysteine. The latter occurs through a pathway called transsulphuration, for which homocysteine acts as an intermediate. Homocysteine metabolism to cysteine requires the assistance of key nutrients as cofactors for enzymes, including several water soluble vitamins. When the supply of cofactors is imbalanced, homocysteine metabolism is perturbed. Much of our knowledge of homocysteine metabolism comes from research examining changes in blood or tissue concentrations in relation to nutrient supply. While important, they do not provide quantitative data as to how much the synthesis of cysteine is hampered. This has important consequences, as the goal in supplying the sulphur amino acids is their provision at rates to meet whole body demands. The current proposal seeks to address this issue by using a whole body model for the measurement of cysteine synthesis through the transsulphuration pathway and to elucidate the specific impacts of varying nutrient supply on this conversion. Over the course of the granting cycle, the proposed research program will lead to the development of a valid model for the assessment of the quantitative partion of homocysteine metabolism. The novelty of the program lies in the integration of whole body and tissue/cellular specific information, which will lead to the development of a holistic picture of the key factors regulating sulphur amino acid metabolism.

含硫氨基酸蛋氨酸在动物细胞中作为蛋白质合成（结构、酶、激素）的底物，作为甲基供体（神经递质合成、DNA稳定性），以及半胱氨酸的合成起着关键作用。 后者通过一种称为转硫作用的途径发生，其中同型半胱氨酸作为中间体。 同型半胱氨酸代谢为半胱氨酸需要关键营养素作为酶的辅因子的帮助，包括几种水溶性维生素。 当辅助因子的供应不平衡时，同型半胱氨酸代谢就会受到干扰。 我们对同型半胱氨酸代谢的大部分知识来自于检查血液或组织浓度变化与营养供应的研究。 虽然重要，但它们没有提供半胱氨酸合成受到多大阻碍的定量数据。 这具有重要的后果，因为供应含硫氨基酸的目标是以满足全身需求的速率提供。 目前的建议旨在解决这个问题，通过使用全身模型测量半胱氨酸合成通过转硫途径，并阐明不同的营养供应对这种转换的具体影响。 在授予周期的过程中，拟议的研究计划将导致开发一个有效的模型，用于评估同型半胱氨酸代谢的定量部分。该计划的新奇之处在于整体和组织/细胞特定信息的整合，这将导致对调节含硫氨基酸代谢的关键因素的整体认识的发展。