The relationship between intracellular and plasma levels of folate and metabolites in the methionine cycle: a model.
The relationship between intracellular and plasma levels of folate and metabolites in the methionine cycle: a model.
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DOI：
10.1002/mnfr.201200125
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发表时间：
2013-04
影响因子：
5.2
通讯作者：
Nijhout, H. Frederik
中科院分区：
文献类型：
--
作者：
Duncan, Tanya M.;Reed, Michael C.;Nijhout, H. Frederik
叶酸状态和蛋氨酸循环的状态通常通过测量血浆中的叶酸和代谢物来评估。人们假设血浆代谢物水平与其在组织中的水平成正比，但几乎没有信息支持这一假设。我们开发了一个数学模型，基于肝脏和组织中蛋氨酸循环的已知动力学，以及代谢产物进出血浆的动力学。该模型准确地再现了叶酸强化前后测得的代谢物值。该模型使我们能够在电子计算机中研究组织和血浆中代谢物值之间的关系，以及这些关系如何随蛋氨酸和维生素B的摄入以及蛋氨酸循环中酶基因的突变而变化。我们探讨了叶酸状态与血浆中代谢物值之间的关系，代谢物值与甲基化能力之间的关系，对蛋氨酸负荷的反应，以及叶酸在血浆和组织中的半衰期。该模型显示，叶酸的高急性摄入量在很大程度上仍局限于血浆，并迅速排出。我们使用该模型来研究唐氏综合征和氧化应激对血浆和组织中代谢物值的影响。
Folate status and the status of the methionine cycle are typically assessed by measuring folate and metabolites in the plasma. It is assumed that plasma metabolite levels are proportional to their levels in tissues, but there is little information to support this assumption. We developed a mathematical model, based on known kinetics of the methionine cycle in the liver and tissues and transport kinetics of metabolites into and out of the plasma. The model accurately reproduces measured metabolite values pre and post folate fortification. The model allows us to study, in silico, the relationships between metabolite values in tissues and plasma, and how these vary with methionine and B vitamin input, and with mutations in the genes for enzymes in the methionine cycle. We explore the relationship between folate status and metabolite values in the plasma, the relationships between metabolite values and methylation capacity, the response to a methionine load, and the half-life of folate in plasma and tissues. The model shows that a high acute intake of folate remains largely restricted to the plasma and is rapidly excreted. We use the model to study the effects of Down syndrome and oxidative stress on metabolite values in plasma and tissues.
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