Pyruvate kinase M2: A simple molecule with complex functions.

Mohammed Alquraishi, Dexter L Puckett, Dina S Alani, Amal S Humidat, Victoria D Frankel, Dallas R Donohoe, Jay Whelan, Ahmed Bettaieb

Journal: Free radical biology & medicine 2020;143():176-192

PMID: 31401304

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Abstract

Pyruvate kinase M2 is a critical enzyme that regulates cell metabolism and growth under different physiological conditions. In its metabolic role, pyruvate kinase M2 catalyzes the last glycolytic step which converts phosphoenolpyruvate to pyruvate with the generation of ATP. Beyond this metabolic role in glycolysis, PKM2 regulates gene expression in the nucleus, phosphorylates several essential proteins that regulate major cell signaling pathways, and contribute to the redox homeostasis of cancer cells. The expression of PKM2 has been demonstrated to be significantly elevated in several types of cancer, and the overall inflammatory response. The unusual pattern of PKM2 expression inspired scientists to investigate the unrevealed functions of PKM2 and the therapeutic potential of targeting PKM2 in cancer and other disorders. Therefore, the purpose of this review is to discuss the mechanistic and therapeutic potential of targeting PKM2 with the focus on cancer metabolism, redox homeostasis, inflammation, and metabolic disorders. This review highlights and provides insight into the metabolic and non-metabolic functions of PKM2 and its relevant association with health and disease.

Address: Department of Nutrition, University of Tennessee Knoxville, Knoxville, TN, 37996-0840, USA.; Department of Nutrition, University of Tennessee Knoxville, Knoxville, TN, 37996-0840, USA; Department of Biochemistry, Cellular and Molecular Biology, University of Tennessee, Knoxville, TN, 37996-0840, USA; Graduate School of Genome Science and Technology, University of Tennessee, Knoxville, TN, 37996-0840, USA. Electronic address: [email protected].

DOI: 10.1016/j.freeradbiomed.2019.08.007