IDH2
小结
IDH2是致癌基因，编码蛋白（异柠檬酸脱氢酶2）是在三羧酸（TCA）循环中催化异柠檬酸氧化脱羧成α-酮戊二酸（α-KG）的一种细胞代谢酶，IDH2利用NADP（+）作为电子受体，它在线粒体中表达，在线粒体中它通过TCA循环在细胞代谢和能量产生中起作用。IDH2催化位点的癌症相关突变赋予新形态酶活性功能获得，允许突变酶将α-KG转化为“oncometabolite”D-2-羟基戊二酸（2-HG），2-HG通过抑制需要α-KG作为底物的多种酶来促进肿瘤发展，包括参与DNA去甲基化，组蛋白去甲基化，适应缺氧和胶原蛋白成熟的酶。IDH2在包括急性髓性白血病和神经胶质瘤在内的各种癌症中反复发生突变。已经在胶质瘤，胆管癌和急性髓性白血病（AML）等中发现了IDH1突变。
IDH2 (isocitrate dehydrogenase 2) protein is an enzyme that catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) in the tricarboxylic acid (TCA) cycle. IDH2 utilizes NADP(+) as an electron acceptor and it is expressed in the mitochondria, where it plays a role in cell metabolism and energy production via TCA cycle. Cancer-associated mutations in the catalytic site of IDH2 confer a gain-of-function of neomorphic enzymatic activity allowing the mutant enzyme to convert α-KG to the “oncometabolite” D-2-hydroxyglutarate (2-HG). 2-HG promotes tumor development by inhibiting a variety of enzymes that require α-KG as a substrate, including enzymes involved in DNA demethylation, histone demethylation, adaptation to hypoxia and collagen maturation. IDH2 mutations have been identified in hematologic malignancies, particularly in acute myeloid leukemia (AML), as well as in solid tumors such as gliomas and cholangiocarcinomas.