Department of Chemical Engineering, Thornton Science Park, University of Chester, UK.
Faculty of Health and Social Care, Edge Hill University, Ormskirk, Lancashire, UK.
Brief Bioinform. 2018 Mar 1;19(2):303-317. doi: 10.1093/bib/bbw116.
Dietary folates have a key role to play in health, as deficiencies in the intake of these B vitamins have been implicated in a wide variety of clinical conditions. The reason for this is folates function as single carbon donors in the synthesis of methionine and nucleotides. Moreover, folates have a vital role to play in the epigenetics of mammalian cells by supplying methyl groups for DNA methylation reactions. Intriguingly, a growing body of experimental evidence suggests that DNA methylation status could be a central modulator of the ageing process. This has important health implications because the methylation status of the human genome could be used to infer age-related disease risk. Thus, it is imperative we further our understanding of the processes which underpin DNA methylation and how these intersect with folate metabolism and ageing. The biochemical and molecular mechanisms, which underpin these processes, are complex. However, computational modelling offers an ideal framework for handling this complexity. A number of computational models have been assembled over the years, but to date, no model has represented the full scope of the interaction between the folate cycle and the reactions, which governs the DNA methylation cycle. In this review, we will discuss several of the models, which have been developed to represent these systems. In addition, we will present a rationale for developing a combined model of folate metabolism and the DNA methylation cycle.
饮食中的叶酸在健康中起着关键作用，因为这些 B 族维生素的摄入不足与多种临床情况有关。原因是叶酸作为一碳供体在蛋氨酸和核苷酸的合成中起作用。此外，叶酸通过为 DNA 甲基化反应提供甲基基团，在哺乳动物细胞的表观遗传学中起着至关重要的作用。有趣的是，越来越多的实验证据表明，DNA 甲基化状态可能是衰老过程的中心调节剂。这具有重要的健康意义，因为人类基因组的甲基化状态可用于推断与年龄相关的疾病风险。因此，我们必须进一步了解支持 DNA 甲基化的过程，以及这些过程如何与叶酸代谢和衰老相互作用。这些过程的生化和分子机制很复杂。然而，计算建模为处理这种复杂性提供了理想的框架。多年来已经组装了许多计算模型，但迄今为止，没有一个模型能够代表叶酸循环与控制 DNA 甲基化循环的反应之间的全部相互作用。在这篇综述中，我们将讨论已经开发出来的几种用于表示这些系统的模型。此外，我们将提出一个理由，即开发叶酸代谢和 DNA 甲基化循环的组合模型。
