CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisbon, Portugal.
Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto, 1099-023 Lisbon, Portugal.
Biomolecules. 2020 Sep 26;10(10):1370. doi: 10.3390/biom10101370.
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.
谷氨酰胺是一种非必需氨基酸，在包括肿瘤细胞在内的增殖细胞的代谢中发挥关键作用。在中枢神经系统 (CNS) 中，谷氨酰胺代谢尤为重要，因为谷氨酰胺-谷氨酸循环是一种通过神经元-星形胶质细胞代谢共生依赖性方式严格调节氨基酸生物利用度来控制谷氨酸衍生神经递质产生的方式。包括恶性神经胶质瘤在内的几种 CNS 恶性肿瘤中已经报道了与谷氨酰胺相关的代谢调整，这些肿瘤被认为是“依赖谷氨酰胺的”。在这些肿瘤中，谷氨酰胺成为一种必需氨基酸，优先用于能量和生物量的产生，包括谷胱甘肽 (GSH) 的生成，这对于控制氧化应激至关重要。因此，在这篇综述中，我们将重点介绍胶质瘤经历的代谢重塑，特别是谷氨酰胺代谢。我们将讨论一些治疗方案，包括针对谷氨酰胺代谢的新研究尝试，以及利用这种改变的特征的诊断策略的简要更新。更好地了解恶性神经胶质瘤细胞的代谢将有助于确定新的分子靶点和设计新的治疗方法。
