Embryonic folate metabolism and mouse neural tube defects
Embryonic folate metabolism and mouse neural tube defects
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DOI：
10.1126/science.280.5372.2107
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发表时间：
1998-06-26
期刊：
影响因子：
56.9
通讯作者：
Copp, AJ
中科院分区：
文献类型：
--
作者：
Fleming, A;Copp, AJ
叶酸可以预防70%的人类神经管缺陷（NTD），但其作用机制尚不清楚。脱氧尿苷抑制试验检测在体外发育NTD的纯合子斑点（Pax3）小鼠胚胎中叶酸代谢的紊乱。在斑点胚胎中[3H]胸苷的过量掺入表明用于嘧啶生物合成的叶酸供应的代谢缺陷。外源性叶酸和胸苷都能纠正斑点纯合子的生物合成缺陷，并防止一些NTDs，而蛋氨酸则有加重作用。这些数据支持叶酸对人类神经形成的直接正常化，并提示叶酸作用的代谢基础。
Folic acid prevents 70 percent of human neural tube defects (NTDs) but its mode of action is unclear. The deoxyuridine suppression test detects disturbance of folate metabolism in homozygous splotch (Pax3) mouse embryos that are developing NTDs in vitro. Excessive incorporation of [(3)H]thymidine in splotch embryos indicates a metabolic deficiency in the supply of folate for the biosynthesis of pyrimidine. Exogenous folic acid and thymidine both correct the biosynthetic defect and prevent some NTDs in splotch homozygotes, whereas methionine has an exacerbating effect. These data support a direct normalization of neurulation by folic acid in humans and suggest a metabolic basis for folate action.