Du Xin, Hu Hai
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Front Cell Dev Biol. 2021 Mar 26;9:651317. doi: 10.3389/fcell.2021.651317. eCollection 2021.
2-Hydroxyglutarate (2-HG) is structurally similar to α-ketoglutarate (α-KG), which is an intermediate product of the tricarboxylic acid (TCA) cycle; it can be generated by reducing the ketone group of α-KG to a hydroxyl group. The significant role that 2-HG plays has been certified in the pathophysiology of 2-hydroxyglutaric aciduria (2HGA), tumors harboring mutant isocitrate dehydrogenase 1/2 (IDH1/2mt), and in clear cell renal cell carcinoma (ccRCC). It is taken as an oncometabolite, raising much attention on its oncogenic mechanism. In recent years, 2-HG has been verified to accumulate in the context of hypoxia or acidic pH, and there are also researches confirming the vital role that 2-HG plays in the fate decision of immune cells. Therefore, 2-HG not only participates in tumorigenesis. This text will also summarize 2-HG's identities besides being an oncometabolite and will discuss their enlightenment for future research and clinical treatment.
2-羟基戊二酸（2-HG）在结构上与α-酮戊二酸（α-KG）相似，α-酮戊二酸是三羧酸（TCA）循环的中间产物；它可以通过将α-KG的酮基还原为羟基而生成。2-HG所起的重要作用已在2-羟基戊二酸尿症（2HGA）、携带异柠檬酸脱氢酶1/2突变体（IDH1/2mt）的肿瘤以及透明细胞肾细胞癌（ccRCC）的病理生理学中得到证实。它被视为一种致癌代谢物，其致癌机制备受关注。近年来，已证实2-HG在缺氧或酸性pH环境中会积累，也有研究证实2-HG在免疫细胞命运决定中起着至关重要的作用。因此，2-HG不仅参与肿瘤发生。本文还将总结2-HG除作为致癌代谢物之外的特性，并讨论它们对未来研究和临床治疗的启示。
