Glutamine metabolism in cancers: Targeting the oxidative homeostasis

Abstract

Glutamine is the most abundant amino acid in blood and tissues, and the most important nutrient except for glucose in cancer cells. Over the past years, most studies have focused on the role of Gln metabolism in supporting energy metabolism rather than maintaining oxidative homeostasis. In fact, Gln is an important factor in maintaining oxidative homeostasis of cancer cells, especially in “Glutamine addicted” cancer cells. Here, this paper will review the recent scientific literature about the link between Gln metabolism and oxidative homeostasis, with an emphasis on the potential role of Gln metabolism in different cancers. Given that oxidative homeostasis is of critical importance in cancer, understanding the impacts of a Gln metabolism on oxidative homeostasis, gaining great insights into underlying molecular mechanisms, and developing effective therapeutic strategies are of great importance.

Nasopharyngeal carcinoma: current views on the tumor microenvironment's impact on drug resistance and clinical outcomes

“…Competition for glutamine uptake also exists between tumor cells and immune cells in the TME. Studies have demonstrated that competitive consumption of glutamine by tumor cells could lead to suppressed antitumor immune response in many cancers [ 138 , 139 ]. Inhibiting glutamine uptake in tumor cells could potentially enhance glucose uptake, indicating that glutamine may serve as the limiting factor in the TME [ 140 ].…”

Immunosurveillance encounters cancer metabolism

“…A raised glutamine metabolism also quenches ROS to compromise oxidative stress by replenishing the mitochondrial NADPH pool through glutathione generation (Gong et al, 2022 ). Indeed, glutamine can facilitate a stem cell phenotype by maintaining the redox status (Liao et al, 2017 ).…”

Critical roles and clinical perspectives of RNA methylation in cancer

“…In the 1950s, the American physiologist Harry Eagle was the first to propose that proliferating cancer cells exhibit an increased requirement for Gln based on the observation that human carcinoma cells (HeLA strain) exhibit higher uptake of Gln than other amino acids 276 . Gln, the most abundant nonessential amino acid in the plasma and tissues, is the most indispensable nutrient besides glucose for cancer metabolism in various cancer types, including pancreatic ductal adenocarcinoma (PDAC), AML, colon cancer, PCa, kidney cancer, lung cancer, liver cancer, and glioma 277–279 . On the one hand, amino acids are metabolized to meet the increased requirements for protein synthesis in proliferating cancer cells.…”

“… 276 Gln, the most abundant nonessential amino acid in the plasma and tissues, is the most indispensable nutrient besides glucose for cancer metabolism in various cancer types, including pancreatic ductal adenocarcinoma (PDAC), AML, colon cancer, PCa, kidney cancer, lung cancer, liver cancer, and glioma. 277 , 278 , 279 On the one hand, amino acids are metabolized to meet the increased requirements for protein synthesis in proliferating cancer cells. On the other hand, the requirement for the catabolism of amino acids, especially Gln, for energy generation and biomass synthesis surpasses that for protein synthesis in cancer cells.…”