Metabolic Rewiring and the Characterization of Oncometabolites
Arthur G. Zupko’s Division of Systems Pharmacology and Pharmacogenomics, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY 11201, USA
Author to whom correspondence should be addressed.
Academic Editors: Giuseppe Broggi and Lucia Salvatorelli
Received: 23 May 2021 / Revised: 31 May 2021 / Accepted: 8 June 2021 / Published: 10 June 2021
Oncometabolites are produced by cancer cells and assist the cancer to proliferate and progress. Oncometabolites occur as a result of mutated enzymes in the tumor tissue or due to hypoxia. These processes result in either the abnormal buildup of a normal metabolite or the accumulation of an unusual metabolite. Definition of the metabolic changes that occur due to these processes has been accomplished using metabolomics, which mainly uses mass spectrometry platforms to define the content of small metabolites that occur in cells, tissues, organs and organisms. The four classical oncometabolites are fumarate, succinate, (2R)-hydroxyglutarate and (2S)-hydroxyglutarate, which operate by inhibiting 2-oxoglutarate-dependent enzyme reactions that principally regulate gene expression and response to hypoxia. Metabolomics has also revealed several putative oncometabolites that include lactate, kynurenine, methylglyoxal, sarcosine, glycine, hypotaurine and (2R,3S)-dihydroxybutanoate. Metabolomics will continue to be critical for understanding the metabolic rewiring involving oncometabolite production that underpins many cancer phenotypes.