Emerging regulatory paradigms in glutathione metabolism

Authors

Yilin Liu, University of Nebraska-LincolnFollow
Annastasia S. Hyde, University of Nebraska-LincolnFollow
Melanie A. Simpson, University of Nebraska-LincolnFollow
Joseph J. Barycki, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

2014

Citation

Adv Cancer Res. 2014 ; 122: 69–101.

Comments

Copyright © 2014 Elsevier Inc. Used by permission.

Abstract

One of the hallmarks of cancer is the ability to generate and withstand unusual levels of oxidative stress. In part, this property of tumor cells is conferred by elevation of the cellular redox buffer glutathione. Though enzymes of the glutathione synthesis and salvage pathways have been characterized for several decades, we still lack a comprehensive understanding of their independent and coordinate regulatory mechanisms. Recent studies have further revealed that overall central metabolic pathways are frequently altered in various tumor types, resulting in significant increases in biosynthetic capacity, and feeding into glutathione synthesis. In this review, we will discuss the enzymes and pathways affecting glutathione flux in cancer, and summarize current models for regulating cellular glutathione through both de novo synthesis and efficient salvage. In addition, we examine the integration of glutathione metabolism with other altered fates of intermediary metabolites, and highlight remaining questions about molecular details of the accepted regulatory modes.