Take Advantage of Glutamine Anaplerosis, the Kernel of the Metabolic Rewiring in Malignant Gliomas

Abstract

Glutamine is a non-essential amino acid that plays a key role in the metabolism of proliferating cells including neoplastic cells. In the central nervous system (CNS), glutamine metabolism is particularly relevant, because the glutamine-glutamate cycle is a way of controlling the production of glutamate-derived neurotransmitters by tightly regulating the bioavailability of the amino acids in a neuron-astrocyte metabolic symbiosis-dependent manner. Glutamine-related metabolic adjustments have been reported in several CNS malignancies including malignant gliomas that are considered ‘glutamine addicted’. In these tumors, glutamine becomes an essential amino acid preferentially used in energy and biomass production including glutathione (GSH) generation, which is crucial in oxidative stress control. Therefore, in this review, we will highlight the metabolic remodeling that gliomas undergo, focusing on glutamine metabolism. We will address some therapeutic regimens including novel research attempts to target glutamine metabolism and a brief update of diagnosis strategies that take advantage of this altered profile. A better understanding of malignant glioma cell metabolism will help in the identification of new molecular targets and the design of new therapies.