Metabolic functions of misunderstood D-2-hydroxyglutarate

Yidong Liu; Zhaoqi Kang; Wen Zhang; Cuiqing Ma; Ping Xu; Chao Gao

doi:10.59717/j.xinn-life.2024.100101

The Innovation Life > 2024 Vol. 2 > No. 4 > 100101

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Metabolic functions of misunderstood D-2-hydroxyglutarate

1.
State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China
2.
Institute of Medical Sciences, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, China
3.
State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, Shanghai 200240, China

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Corresponding authors: wenzhang@sdu.edu.cn (W.Z.); jieerbu@sdu.edu.cn (C.G.)
Received Date: July 16, 2024

Accepted Date: October 31, 2024

Published Online: November 13, 2024

The Innovation Life 2(4), https://doi.org/10.59717/j.xinn-life.2024.100101 | Cite this article

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GRAPHICAL ABSTRACT

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PUBLIC SUMMARY

PUBLIC SUMMARY
1. D-2-Hydroxyglutarate (D-2-HG) is known as an oncometabolite that promotes the genesis of various tumors.
  
  D-2-HG is also a functional endogenous metabolite involved in many core metabolic processes.
  
  D-2-HG production by transhydrogenases facilitates thermodynamically unfavorable but necessary reactions.
  
  D-2-HG is an intermediate metabolite of D/L-lysine, propionyl-CoA, and L-glutamate catabolism.
  
  D-2-HG metabolism-related proteins have potential applications in synthetic biology and medicine.

ABSTRACT

ABSTRACT

Isocitrate dehydrogenase mutation-induced D-2-hydroxyglutarate (D-2-HG) accumulation may promote the tumorigenesis of numerous cancers. D-2-HG produced by several promiscuous enzymatic reactions under normal conditions is also toxic to organisms. D-2-HG was thus previously viewed as an abnormal metabolite with no physiological function and D-2-HG conversion to 2-ketoglutarate by D-2-HG dehydrogenase seems to be a process of metabolite repair. However, several recent studies have revealed that D-2-HG production is not a meaningless process without a physiological purpose. D-2-HG production actually participates in many core metabolic processes, and disorders of these processes may be the reason for the D-2-HG accumulation in some tumors lacking the isocitrate dehydrogenase mutation. This review summarizes the diverse and widely distributed metabolic processes involving D-2-HG, highlights the physiological functions of D-2-HG generation from various precursors, and discusses the possible applications of enzymes related to D-2-HG metabolism in synthetic biology, diagnosis, and treatment of D-2-HG accumulation-induced diseases.

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Liu Y., Kang Z., Zhang W., et al., (2024). Metabolic functions of misunderstood D-2-hydroxyglutarate. The Innovation Life 2(4): 100101. https://doi.org/10.59717/j.xinn-life.2024.100101

Liu Y., Kang Z., Zhang W., et al., (2024). Metabolic functions of misunderstood D-2-hydroxyglutarate. The Innovation Life 2(4): 100101. https://doi.org/10.59717/j.xinn-life.2024.100101

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