Homocysteine and neural tube defects
Homocysteine and neural tube defects
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DOI：
10.1093/jn/126.suppl_3.756s
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发表时间：
1996-03-01
影响因子：
4.2
通讯作者：
Lee, YJ
中科院分区：
文献类型：
--
作者：
Mills, JL;Scott, JM;Lee, YJ
现在已经确定，叶酸，当采取围怀孕期，可以防止许多神经管缺陷。人们也越来越清楚，叶酸不能纠正孕妇的营养缺乏。相反，似乎代谢缺陷是导致这些神经管缺陷的原因，并且这种缺陷或缺陷可以通过足够大剂量的叶酸来纠正。我们最近的工作表明，同型半胱氨酸代谢可能是叶酸影响的关键途径。我们已经证明了携带受影响胎儿的妇女的同型半胱氨酸水平明显高于对照组妇女。这些发现表明，其中一种负责同型半胱氨酸代谢的酶可能在受影响的妊娠中异常。动物研究表明，同型半胱氨酸转化为蛋氨酸可能是关键步骤。培养中的大鼠胚胎需要蛋氨酸来关闭神经管。甲硫氨酸合酶、胱硫醚合酶和5，10亚甲基四氢叶酸还原酶在人类同型半胱氨酸的代谢中都是重要的。如果甲硫氨酸合酶是关键酶，这将引起一个有趣的公共卫生问题，即维生素B-12可能像叶酸一样能够刺激异常酶。添加维生素B-12可能会减少强化食品中所需的叶酸剂量，从而减轻对叶酸过量的担忧。
It is now well established that folic acid, when taken periconceptionally, can prevent many neural tube defects. It is also becoming clear that folic acid does not work by correcting a nutritional deficiency in pregnant women. Rather, it appears that a metabolic defect is responsible for these neural tube defects and that this defect or defects can be corrected by a sufficiently large dose of folic acid. Our recent work demonstrates that homocysteine metabolism is likely to be the critical pathway affected by folic acid. We have demonstrated significantly higher homocysteine levels in women carrying affected fetuses than in control women. These findings indicate that one of the enzymes responsible for homocysteine metabolism is likely to be abnormal in affected pregnancies. Animal studies suggest that the conversion of homocysteine to methionine could be the critical step. Rat embryos in culture require methionine for neural tube closure. Methionine synthase, cystathionine synthase, and 5,10 methylene tetrahydrofolate reductase are all important in the metabolism of homocysteine in humans. If methionine synthase is the critical enzyme, it would raise the interesting public health issue that vitamin B-12 might be able to stimulate the abnormal enzyme as folic acid does. Adding vitamin B-12 might make it possible to reduce the dose of folic acid required in fortified food, thus allaying concerns about overexposure to folic acid.