Novel Insight into 2-Hydroxyglutarate Production in Human CellsHe J1, Zhao Z3, Xu G2 and Liu Y1*
- *Corresponding Author:
- Liu Y
Department of Biotechnology
Center for Translational Medicine
Dalian Institute of Chemical Physics
Chinese Academy of Sciences
457 Zhongshan Rd, Room 114 Dalian
Liaoning, 116023, China
E-mail: [email protected]
Received date: November 29, 2015; Accepted date: December 14, 2015; Published date: December 16, 2015
Citation: He J, Zhao Z, Xu G, Liu Y (2015) Novel Insight into 2-Hydroxyglutarate Production in Human Cells. Metabolomics 5:159. doi:10.4172/2153-0769.1000159
Copyright: © 2015 He J, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Mutations in metabolic enzymes, especially Isocitrate dehydrogenase1/2, strongly implicate altered metabolism in tumorigenesis by generating 2-HG. 2-HG is an oncometabolite mostly identified in AML and glioma. Wild type IDH1 and IDH2 catalyze the interconversion of isocitrate and α-KG, which is a TCA cycle intermediate and an essential cofactor for many enzymes, while 2-HG produced by mutant of IDH1/2 functions as a competitive inhibitor of α-KG, leading to epigenetic alteration and disruption of PHDs-mediated protein hydroxylation. However how is 2-HG produced in non-IDH mutated cells is still not well defined. Recent studies demonstrated that the accumulation of 2-HG in non-IDH mutated cells might be due to many other cellular mechanisms, including MYC status, expression of IDH1/2, dysregulation of 2-HGDH and hypoxia. Here we review what is known about the molecular mechanisms of transformation by IDH mutations and the mechanisms of carcinogenic metabolites 2-HG accumulation in non-IDH mutated cells. We also discuss the strategies for separation of two enantiomers of 2-HG (D and L) and their implications for the identification of the cancer subtypes and the development of targeted therapies to treat different types of human malignancies.