Diet, methyl donors and DNA methylation: Interactions between dietary folate, methionine and choline
Diet, methyl donors and DNA methylation: Interactions between dietary folate, methionine and choline
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DOI：
10.1093/jn/132.8.2333s
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发表时间：
2002-08-01
影响因子：
4.2
通讯作者：
Zeisel, SH
中科院分区：
文献类型：
--
作者：
Niculescu, MD;Zeisel, SH
甲基化影响某些基因的表达，并依赖于S-腺苷甲硫氨酸的甲基可获得性。膳食甲基来源于含有蛋氨酸、一碳单位和胆碱(或胆碱代谢物甜菜碱)的食物。人类每天摄入大约50毫摩尔的甲基团；其中60%来自胆碱。转甲基化代谢途径将胆碱、蛋氨酸、甲基四氢叶酸(甲基-四氢叶酸)以及维生素B-6和B-12紧密联系在一起。这些途径在同型半胱氨酸形成蛋氨酸的过程中相交。扰乱其中一条途径的新陈代谢会导致其他途径的代偿性变化。例如，可以使用甲基-四氢呋喃的甲基基团或从胆碱衍生的甜菜碱甲基基团从同型半胱氨酸生成蛋氨酸。类似地，甲基四氢呋喃可以由丝氨酸或胆碱的甲基基团通过二甲甘氨酸形成，而胆碱可以通过甲硫氨酸的甲基从头合成(通过SAM)。当动物和人类被剥夺胆碱时，他们会使用更多的甲基-四氢呋喃来重新甲基化肝脏中的同型半胱氨酸，并增加饮食中的叶酸需求。相反，当他们缺乏叶酸时，他们会从胆碱中使用更多的甲基，从而增加了对胆碱的饮食需求。转基因和基因敲除小鼠的出现使进一步的研究成为可能，证明了这些甲基来源之间的相互关系。综上所述，当我们考虑饮食需求和对DNA甲基化的可能影响时，重要的是要认识到蛋氨酸、甲基四氢呋喃和胆碱可以是甲基的替代来源，我们的研究设计应该反映这一点。
DNA methylation influences the expression of some genes and depends upon the availability of methyl groups from S-adenosylmethionine (SAM). Dietary methyl groups derive from foods that contain methionine, one-carbon units and choline (or the choline metabolite betaine). Humans ingest similar to50 mmol of methyl groups per day; 60% of them are derived from choline. Transmethylation metabolic pathways closely interconnect choline, methionine, methyltetrahydrofolate (methyl-THF) and vitamins B-6 and B-12. The pathways intersect at the formation of methionine from homocysteine. Perturbing the metabolism of one of these pathways results in compensatory changes in the others. For example, methionine can be formed from homocysteine using methyl groups from methyl-THF, or using methyl groups from betaine that are derived from choline. Similarly, methyl-THF can be formed from one-carbon units derived from serine or from the methyl groups of choline via dimethylglycine, and choline can be synthesized de novo using methyl groups derived from methionine (via SAM). When animals and humans are deprived of choline, they use more methyl-THF to remethylate homocysteine in the liver and increase dietary folate requirements. Conversely, when they are deprived of folate, they use more methyl groups from choline, increasing the dietary requirement for choline. The availability of transgenic and knockout mice has made possible additional studies that demonstrate the interrelationship of these methyl sources. In summary, as we consider dietary requirements and possible effects on DNA methylation, it is important to realize that methionine, methyl-THF and choline can be fungible sources of methyl groups, and the design of our studies should reflect this.