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谷氨酰胺在细胞代谢中的依赖性。

Glutamine reliance in cell metabolism.

机构信息

Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, 21983, South Korea.

Department of Integrated OMICS for Biomedical Science, Yonsei University, Seoul, 03722, South Korea.

出版信息

Exp Mol Med. 2020 Sep;52(9):1496-1516. doi: 10.1038/s12276-020-00504-8. Epub 2020 Sep 17.

Abstract

As knowledge of cell metabolism has advanced, glutamine has been considered an important amino acid that supplies carbon and nitrogen to fuel biosynthesis. A recent study provided a new perspective on mitochondrial glutamine metabolism, offering mechanistic insights into metabolic adaptation during tumor hypoxia, the emergence of drug resistance, and glutaminolysis-induced metabolic reprogramming and presenting metabolic strategies to target glutamine metabolism in cancer cells. In this review, we introduce the various biosynthetic and bioenergetic roles of glutamine based on the compartmentalization of glutamine metabolism to explain why cells exhibit metabolic reliance on glutamine. Additionally, we examined whether glutamine derivatives contribute to epigenetic regulation associated with tumorigenesis. In addition, in discussing glutamine transporters, we propose a metabolic target for therapeutic intervention in cancer.

摘要

随着细胞代谢知识的进步,谷氨酰胺已被认为是一种重要的氨基酸,可为生物合成提供碳和氮源。最近的一项研究为线粒体谷氨酰胺代谢提供了新的视角,为肿瘤缺氧、药物耐药性的出现、谷氨酰胺分解代谢引起的代谢重编程以及代谢策略提供了机制见解,以针对癌细胞中的谷氨酰胺代谢。在这篇综述中,我们根据谷氨酰胺代谢的区室化介绍了谷氨酰胺的各种生物合成和生物能量作用,以解释为什么细胞表现出对谷氨酰胺的代谢依赖。此外,我们还研究了谷氨酰胺衍生物是否有助于与肿瘤发生相关的表观遗传调控。此外,在讨论谷氨酰胺转运体时,我们为癌症的治疗干预提出了一个代谢靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f530/8080614/f0b29a3d6910/12276_2020_504_Fig1_HTML.jpg

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