Lifting the veil on tumor metabolism: A GDH1-focused perspective

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-05-03 DOI:10.1016/j.isci.2025.112551

Sisi Zhou , Huaer Wu , Yun Chen , Jiawei Lv , Shufang Chen , Hua Yu , Tiezhu Shi , Xiongjun Wang , Lingyun Xiao

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引用次数: 0

Abstract

Tumors depend on glutamine for energy production, biosynthesis, and redox homeostasis. Glutamate dehydrogenase 1 (GDH1) primarily catalyzes the oxidative deamination of glutamate to α-ketoglutarate (α-KG) and ammonia, utilizing NAD⁺ or NADP⁺ as cofactors. α-KG is a tricarboxylic acid (TCA) cycle intermediate at the nexus of multiple metabolic pathways, fueling the TCA cycle for energy production or providing intermediates essential for lipid, amino acid, and nucleotide synthesis. Its derivatives, succinate and fumarate, function as oncometabolites that promote tumor progression through diverse mechanisms. Additionally, α-KG is an essential cofactor for α-KG-dependent dioxygenases (2-OGDDs), regulating epigenetic modifications that drive tumorigenesis. GDH1 may also catalyze the reductive amination of α-KG to glutamate under glutamine deprivation or hypoxic conditions. The roles of GDH1 in tumors are context-dependent, influencing progression through metabolic and epigenetic mechanisms. This review discusses GDH1’s multifaceted functions and advances in targeting it for cancer therapy.

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揭开肿瘤代谢的面纱：以gdh1为重点的视角

肿瘤依赖谷氨酰胺进行能量产生、生物合成和氧化还原稳态。谷氨酸脱氢酶1 （GDH1）主要利用NAD+或NADP+作为辅助因子，催化谷氨酸氧化脱胺生成α-酮戊二酸（α-KG）和氨。α-KG是一种三羧酸（TCA）循环中间体，在多种代谢途径的联系中，为TCA循环提供能量，或为脂质、氨基酸和核苷酸合成提供必需的中间体。其衍生物琥珀酸盐和富马酸盐作为肿瘤代谢物，通过多种机制促进肿瘤进展。此外，α-KG是α-KG依赖性双加氧酶（2- ogdd）的重要辅助因子，调节驱动肿瘤发生的表观遗传修饰。GDH1也可能在谷氨酰胺剥夺或缺氧条件下催化α-KG还原胺化成谷氨酸。GDH1在肿瘤中的作用是上下文依赖的，通过代谢和表观遗传机制影响肿瘤的进展。本文综述了GDH1的多种功能及其在肿瘤靶向治疗中的研究进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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