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Author:
Date:
2016-08-20
[Abstract] Two enantiomers of 2-hydroxyglutarate (2HG), L (L2HG) and D (D2HG), are metabolites of unknown function in mammalian cells that were initially associated with separate and rare inborn errors of metabolism resulting in increased urinary excretion of 2HG linked to neurological deficits in children (Chalmers et al., 1980; Duran et al., 1980; Kranendijk et al., 2012). More recently, investigators have shown that D2HG is produced by mutant isocitrate dehydrogenase enzymes associated with a variety of human malignancies, such as acute myeloid leukemia, glioblastoma multiforme, and cholangiocarcinoma (Cairns and Mak, 2013; Dang et al., 2009; Ward et al., 2010). By contrast, we and others have shown that L2HG accumulates in response to cellular ...
[摘要] 2-羟基戊二酸（2HG），L（L2HG）和D（D2HG）的两种对映异构体是哺乳动物细胞中未知功能的代谢物，其最初与分开的和罕见的代谢的先天性错误相关，导致与神经系统相关的2HG的尿排泄增加儿童中的缺陷（Chalmers等人，1980; Duran等人，1980; Kranendijk等人，2012）。最近，研究者已经表明，D2HG由与多种人类恶性肿瘤相关的突变体异柠檬酸脱氢酶产生，所述人类恶性肿瘤例如急性骨髓性白血病，多形性成胶质细胞瘤和胆管癌（Cairns和Mak，2013; Dang等人，2009; Ward等人，2010）。相比之下，我们和其他人已经显示L2HG响应于细胞还原应激物如缺氧，缺氧诱导因子的激活和线粒体电子传递链缺陷而累积（Oldham等人，2015; Reinecke 2011; Intlekofer等人，2015; ...
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