Nutritional regulation of homocysteine metabolism

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）和氨基酸半胱氨酸的合成起着关键作用。后者通过一种称为转化的途径发生，其中同型半胱氨酸作为中间物。同型半胱氨酸到半胱氨酸的代谢需要关键营养素作为酶的辅助因子的帮助，包括几种水溶性维生素。当辅因子供应不平衡时，同型半胱氨酸代谢紊乱。我们对同型半胱氨酸代谢的大部分知识来自于对血液或组织浓度变化与营养供应关系的研究。虽然很重要，但它们并没有提供半胱氨酸合成受到多大阻碍的定量数据。这有重要的后果，因为提供含硫氨基酸的目标是以满足全身需求的速度提供。目前的建议试图通过使用一个全身模型来测量通过转化途径合成的半胱氨酸，并阐明不同的营养供应对这种转化的具体影响，从而解决这一问题。在整个资助周期内，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。该计划的新颖之处在于整合了整个身体和组织/细胞的特定信息，这将导致对调节硫氨基酸代谢的关键因素的整体图景的发展。

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.