Instituto de Investigación Biomédica de Málaga (IBIMA), Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, E-29071 Málaga, Spain.
Institute of Veterinary Physiology and Biochemistry, Justus Liebig University of Giessen, D-35392 Giessen, Germany.
Semin Cell Dev Biol. 2020 Feb;98:34-43. doi: 10.1016/j.semcdb.2019.05.012. Epub 2019 May 22.
Metabolic reprogramming in cancer targets glutamine metabolism as a key mechanism to provide energy, biosynthetic precursors and redox requirements to allow the massive proliferation of tumor cells. Glutamine is also a signaling molecule involved in essential pathways regulated by oncogenes and tumor suppressor factors. Glutaminase isoenzymes are critical proteins to control glutaminolysis, a key metabolic pathway for cell proliferation and survival that directs neoplasms' fate. Adaptive glutamine metabolism can be altered by different metabolic therapies, including the use of specific allosteric inhibitors of glutaminase that can evoke synergistic effects for the therapy of cancer patients. We also review other clinical applications of in vivo assessment of glutaminolysis by metabolomic approaches, including diagnosis and monitoring of cancer.
肿瘤中的代谢重编程将谷氨酰胺代谢作为一种关键机制，为肿瘤细胞的大量增殖提供能量、生物合成前体和氧化还原需求。谷氨酰胺也是一种信号分子，参与由癌基因和肿瘤抑制因子调节的基本途径。谷氨酰胺酶同工酶是控制谷氨酰胺分解的关键蛋白，谷氨酰胺分解是细胞增殖和存活的关键代谢途径，决定着肿瘤的命运。适应性谷氨酰胺代谢可以通过不同的代谢治疗来改变，包括使用谷氨酰胺酶的特异性别构抑制剂，这可以为癌症患者的治疗产生协同效应。我们还回顾了通过代谢组学方法对体内谷氨酰胺分解进行评估的其他临床应用，包括癌症的诊断和监测。
