很久没有更新，主要是太忙碌，最近我的一篇文章发表，说明EGCG能改善GDH获得功能突变引发的高胰岛素性低血糖，作用是EGCG结合在GDH的ADP位点，由于劫持了这个刺激位点，导致酶功能被抑制。

绿茶里的茶多酚EGCG对氨基酸分解代谢的关键酶，谷氨酸脱氢酶（GDH）有明显的抑制作用，最近的文章发现了其抑制作用的机理和应用价值。
GDH的活性受到很多小分子的调节，包括抑制剂GTP和刺激剂ADP。EGCG能抑制这个酶的活性，主要原因是EGCG结合到了ADP的位点，占据了刺激位点导致酶的功能被抑制。
GDH的获得功能突变能导致先天性高胰岛素高血氨综合征，胰岛beta细胞特异性表达GDH获得功能突变的小鼠，有低血糖的表现，EGCG能通过抑制GDH转基因鼠的胰岛素分泌达到升高血糖的目的。
另外癌细胞的代谢在很大程度上依赖氨基酸，GDH在癌细胞代谢中发挥很重要的作用，EGCG能否通过抑制氨基酸的分解代谢达到抑制某些种类癌细胞增长的目的，则需要更多的实验观察验证。
这么看人喝茶的结果，喝茶可以抑制氨基酸的分解代谢，这样可以保证在进食蛋白质非常有限的情况下，保持氨基酸用于合成蛋白，而不是被代谢掉，是否如此，还需要很多研究。

题目：GREEN TEA POLYPHENOLS CONTROL DYSREGULATED GLUTAMATE DEHYDROGENASE IN TRANSGENIC MICE BY HIJACKING THE ADP ACTIVATION SITE

摘要：Glutamate dehydrogenase (GDH) catalyzes the oxidative deamination of L-glutamate and, in animals, is extensively regulated by a number of metabolites. Gain of function mutations in GDH that abrogate GTP inhibition causes the hyperinsulinism/hyperammonemia syndrome (HHS), resulting in increased pancreatic β-cells responsiveness to leucine and susceptibility to hypoglycemia following high protein meals. We have previously shown that two of the polyphenols from green tea (EGCG and ECG) inhibit GDH in-vitro and that EGCG blocks GDH-mediated insulin secretion in wild type rat islets. Using structural and site-directed mutagenesis studies, we demonstrate that ECG binds to the same site as the allosteric regulator, ADP. Perifusion assays using pancreatic islets from transgenic mice expressing a human HHS form of GDH demonstrate that the hyper-response to glutamine caused by dysregulated GDH is blocked by the addition of EGCG. As observed in HHS patients, these transgenic mice are hypersensitive to amino acid feeding and this is abrogated by oral administration of EGCG prior to challenge. Finally, the low basal blood glucose level in the HHS mouse model is improved upon chronic administration of EGCG. These results suggest that this common natural product, or some derivative thereof, may prove useful in controlling this genetic disorder. Of broader clinical implication is that other groups have shown restriction of glutamine catabolism via these GDH inhibitors can be useful in treating various tumors. This HHS transgenic mouse model offers a highly useful means to test these agents in-vivo.