Folate status modulates the induction of hepatic glycine N-methyltransferase and homocysteine metabolism in diabetic rats.
Folate status modulates the induction of hepatic glycine N-methyltransferase and homocysteine metabolism in diabetic rats.
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叶酸状态调节糖尿病大鼠肝甘氨酸 N-甲基转移酶和同型半胱氨酸代谢的诱导。
DOI：
10.1152/ajpendo.00237.2006
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Schalinske,KevinL
中科院分区：
文献类型：
--
作者：
Nieman,KristinM;Hartz,CaraS;Szegedi,SandraS;Garrow,TimothyA;Sparks,JanetD;Schalinske,KevinL
糖尿病状态诱导甘氨酸N-甲基转移酶（GNMT）的活性和丰度，GNMT是调节叶酸、甲基和同型半胱氨酸代谢的关键蛋白质。由于叶酸依赖性一碳库是甲基的来源，并且5-甲基四氢叶酸变构抑制GNMT，因此本研究的目的是确定叶酸状态是否对糖尿病和甲基代谢之间的相互作用产生影响。给大鼠喂食含有不足（0 ppm）、充足（2 ppm）或补充（8 ppm）叶酸的饮食30天，之后通过链脲佐菌素治疗在一半的大鼠中引发糖尿病。GNMT，磷脂酰乙醇胺N-甲基转移酶（PEMT），甜菜碱-同型半胱氨酸S-甲基转移酶（BHMT）的活动增加了约2倍，在糖尿病大鼠肝脏;叶酸缺乏导致GNMT活性的最大升高。糖尿病大鼠GNMT蛋白和mRNA以及BHMT mRNA的丰度也升高。叶酸缺乏大鼠的显着高同型半胱氨酸血症被链脲佐菌素减弱，可能部分是由于BHMT表达增加。这些结果表明，糖尿病状态深刻地调节甲基，胆碱和同型半胱氨酸代谢，叶酸状态可能在这些改变的程度中发挥作用。此外，BHMT和PEMT的上调可能表明在糖尿病大鼠中增加的胆碱需求。
A diabetic state induces the activity and abundance of glycineN-methyltransferase (GNMT), a key protein in the regulation of folate, methyl group, and homocysteine metabolism. Because the folate-dependent one-carbon pool is a source of methyl groups and 5-methyltetrahydrofolate allosterically inhibits GNMT, the aim of this study was to determine whether folate status has an impact on the interaction between diabetes and methyl group metabolism. Rats were fed a diet containing deficient (0 ppm), adequate (2 ppm), or supplemental (8 ppm) folate for 30 days, after which diabetes was initiated in one-half of the rats by streptozotocin treatment. The activities of GNMT, phosphatidylethanolamineN-methyltransferase (PEMT), and betaine-homocysteineS-methyltransferase (BHMT) were increased about twofold in diabetic rat liver; folate deficiency resulted in the greatest elevation in GNMT activity. The abundance of GNMT protein and mRNA, as well as BHMT mRNA, was also elevated in diabetic rats. The marked hyperhomocysteinemia in folate-deficient rats was attenuated by streptozotocin, likely due in part to increased BHMT expression. These results indicate that a diabetic state profoundly modulates methyl group, choline, and homocysteine metabolism, and folate status may play a role in the extent of these alterations. Moreover, the upregulation of BHMT and PEMT may indicate an increased choline requirement in the diabetic rat.
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发表时间：
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