Sadre-Marandi Farrah, Dahdoul Thabat, Reed Michael C, Nijhout H Frederik
Mathematical Biosciences Institute, The Ohio State University, Columbus, 43210, OH, USA.
Department of Mathematics, Cal-State Fullerton, Fullerton, 92831, CA, USA.
BMC Syst Biol. 2018 Oct 24;12(1):89. doi: 10.1186/s12918-018-0621-7.
There are large differences between men and women of child-bearing age in the expression level of 5 key enzymes in one-carbon metabolism almost certainly caused by the sex hormones. These male-female differences in one-carbon metabolism are greatly accentuated during pregnancy. Thus, understanding the origin and consequences of sex differences in one-carbon metabolism is important for precision medicine.
We have created a mathematical model of hepatic one-carbon metabolism based on the underlying physiology and biochemistry. We use the model to investigate the consequences of sex differences in gene expression. We give a mechanistic understanding of observed concentration differences in one-carbon metabolism and explain why women have lower S-andenosylmethionine, lower homocysteine, and higher choline and betaine. We give a new explanation of the well known phenomenon that folate supplementation lowers homocysteine and we show how to use the model to investigate the effects of vitamin deficiencies, gene polymorphisms, and nutrient input changes.
Our model of hepatic one-carbon metabolism is a useful platform for investigating the mechanistic reasons that underlie known associations between metabolites. In particular, we explain how gene expression differences lead to metabolic differences between males and females.
育龄期男性和女性在一碳代谢中5种关键酶的表达水平存在很大差异，几乎可以肯定这是由性激素引起的。在孕期，一碳代谢中的这些男女差异会大大加剧。因此，了解一碳代谢中性别差异的起源和后果对于精准医学很重要。
我们基于基础生理学和生物化学创建了肝脏一碳代谢的数学模型。我们使用该模型研究基因表达中性别差异的后果。我们对一碳代谢中观察到的浓度差异给出了机制性理解，并解释了为什么女性的S-腺苷甲硫氨酸水平较低、同型半胱氨酸水平较低、胆碱和甜菜碱水平较高。我们对叶酸补充可降低同型半胱氨酸这一众所周知的现象给出了新的解释，并展示了如何使用该模型来研究维生素缺乏、基因多态性和营养输入变化的影响。
我们的肝脏一碳代谢模型是一个有用的平台，可用于研究代谢物之间已知关联背后的机制原因。特别是，我们解释了基因表达差异如何导致男性和女性之间的代谢差异。
