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Last update 08 May 2025

GLUD1

Last update 08 May 2025

Basic Info

Synonyms

GDH, GDH 1, GLUD

+ [3]

Introduction

Mitochondrial glutamate dehydrogenase that catalyzes the conversion of L-glutamate into alpha-ketoglutarate. Plays a key role in glutamine anaplerosis by producing alpha-ketoglutarate, an important intermediate in the tricarboxylic acid cycle (PubMed:11032875, PubMed:11254391, PubMed:16023112, PubMed:16959573). Plays a role in insulin homeostasis (PubMed:11297618, PubMed:9571255). May be involved in learning and memory reactions by increasing the turnover of the excitatory neurotransmitter glutamate (By similarity).

Drugs associated with GLUD1

GLUD1 inhibitor (CD3)

Target

GLUD1

Mechanism

GLUD1 inhibitors

Active Org.

Centre for Drug Design & Discovery

Originator Org.

Centre for Drug Design & Discovery

Active Indication

Muscular Atrophy

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

GLUD1 inhibitors (CD3)

Target

GLUD1

Mechanism

GLUD1 inhibitors

Active Org.

Centre for Drug Design & Discovery

Originator Org.

Centre for Drug Design & Discovery

Active Indication

Muscular Atrophy

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GLUD1

100 Translational Medicine associated with GLUD1

0 Patents (Medical) associated with GLUD1

554

Literatures (Medical) associated with GLUD1

01 Jul 2025·Phytomedicine

Decoding gelsenicine-induced neurotoxicity in mice via metabolomics and network toxicology

Article

Author: Zhai, Jinxiao ; Jiang, Chen ; Ma, Chunling ; Xie, Bing ; Liu, Minghao ; Yan, Hui ; Cong, Bin ; Wen, Di ; Jin, Mingyang

BACKGROUNDGelsenicine, the most toxic constituent of Gelsemium elegans Benth., is known for its diverse pharmacological activities alongside potent neurotoxicity, frequently leading to poisoning incidents following mistaken ingestion. However, its molecular mechanisms remain largely unexplored.PURPOSEThis study aimed to elucidate the key mechanistic network underlying gelsenicine-induced neurotoxicity by employing a comprehensive strategy that integrated metabolomics, network toxicology, molecular docking, and experimental validation.METHODSAcute oral toxicity tests were conducted in C57BL/6J mice to assess toxic symptoms, determine the median lethal dose (LD₅₀), and evaluate histopathological changes. Untargeted metabolomics was performed to identify differential metabolites and associated pathways in serum, hippocampus (HIP), and medulla oblongata (MO). Integration of network toxicology pinpointed core targets and pathways, which were further validated through molecular docking and RT-qPCR. A core "compound-target-metabolite-pathway" network involved in gelsenicine-induced neurotoxicity was established.RESULTSGelsenicine exhibited an oral LD₅₀ of approximately 1.82 mg/kg and induced neurotoxic damage in the HIP and MO. Two untargeted metabolomic approaches detected a broad range of metabolites, revealing that gelsenicine markedly altered the metabolic profiles of serum, HIP, and MO. Network toxicology analysis identified 187 key targets associated with gelsenicine neurotoxicity. Integrated analyses with the predicted targets of differential metabolites indicated that gelsenicine primarily interferes with the energy metabolism network centered on the malate-aspartate shuttle (MAS), affecting pathways such as carbon metabolism, amino acid metabolism, TCA cycle, and PPAR signaling pathway. Malate, glutamate, and aspartate were identified as core metabolites and potential biomarkers of gelsenicine poisoning. RT-qPCR validation revealed that gelsenicine interfered with the expression of core targets, including GLUD1, MDH, GOT and ME, all of which exhibited good binding energy with gelsenicine.CONCLUSIONThis study unveiled a novel mechanistic insight into gelsenicine-induced neurotoxicity, demonstrating its capacity to perturb multiple energy metabolism pathways associated with MAS. These findings could enhance the theoretical understanding of gelsenicine's neurotoxic effects and highlight potential applications in clinical diagnosis and forensic identification.

01 Jun 2025·The Journal of Nutritional Biochemistry

Naringenin alleviates heat stress-induced liver injury in Ningdu yellow chickens by decreasing RIPK3 and PDC binding

Article

Author: Cai, Gaofeng ; Zheng, Zhanhong ; Liu, Zhenni ; Guo, Xiaoquan ; Qi, Qiurong ; Tang, Ruoyun ; Lin, Siting ; Liu, Ping ; Gao, Xiaona

Naringenin, a flavonoid extract, possesses anti-inflammatory, antioxidant, hepatoprotective, antitumor, and antineurotoxic properties. This study investigated the antiheat stress effects in broilers by adding 200mg/kg naringenin to the diet of Ningdu yellow chicken under heat stress conditions. Heat stress conditions was controlled at 37±2°C (7:00 a.m.-7:00 p.m.) and 24±2°C (7:00 p.m.-7:00 a.m.) at humidity maintained at 60-65%. The results suggest that naringenin elevated the body weight and the ratio of liver mass to weight of Ningdu yellow chicken significantly. Additionally, naringenin significantly reduces heat stress level, improves liver function and antioxidant capacity. Meanwhile, the levels of necroptosis indexes (CYLD, RIPK1, RIPK3 and MLKL) and oxidative stress indexes (PDC, PYGL, GLUL and GLUD1) are downregulated by naringenin. Naringenin mitigated liver damage by decreasing inflammatory indexes caused by heat stress, including NF-κB, IL-1β, IL-18 and HMGB1. This anti-inflammatory effect arose through the downlink binding of the necroptosis index (RIPK3) and the oxidative stress index (PDC) as shown in results of fluorescence co-localization and co-immunoprecipitation. The use of naringenin in poultry may be a possible feed additive to address clinical heat stress.

07 Mar 2025·Neuro-Oncology

Glutamate dehydrogenase 1-catalytic glutaminolysis feedback activates EGFR/PI3K/AKT pathway and reprograms glioblastoma metabolism

Article

Author: Wang, Li ; Li, Haibin ; Li, Yanping ; Meng, Zhen ; Wei, Xiaonan ; Zhang, Guanghui ; Yan, Siyuan ; Wang, Shanshan ; Yang, Rui ; Cui, Hongjuan

AbstractBackgroundGlutamine is an important nutrient for cancer cell growth that provides biological sources for nucleic acid and fatty acid synthesis, but the role of glutaminolysis in signal transduction and glioblastoma (GBM) progression remains little known.MethodsKnockdown and overexpression cells were obtained to explore the functional roles of glutamate dehydrogenase 1 (GDH1) in cell proliferation, tumor formation, and aerobic glycolysis. RNA-seq, Chromatin immunoprecipitation, luciferase assay, and western blot were performed to verify the regulation of the EGFR-AKT pathway by the GDH1 (also known as GLUD1) and KDM6A. Metabolite-level measurements and Seahorse Assay were performed to assess the functional role of GHD1 in reprogramming glycolysis.ResultsHere, we report that GDH1 catalytic glutaminolysis is essential for GBM cell line proliferation and brain tumorigenesis even in high-glucose conditions. Glutamine is metabolized through glutaminolysis to produce α-ketoglutarate (α-KG). We demonstrate that glutamine in combination with leucine activates mammalian TORC1 by enhancing glutaminolysis and α-KG production. α-KG increases the transcription of PDPK1 by reducing the suppressive histone modification H3K27me3 and then promotes the activation of the PI3K/AKT/mTOR pathway. This transcriptional activation induced by α-KG requires histone demethylase KDM6A, which is a 2-oxoglutarate oxygenase that plays an important role in converting α-KG to succinate. Furthermore, we show that GDH1-catalytic glutaminolysis also increases the expression of HK2 and promotes glycolysis in high-glucose conditions dependent on KDM6A-mediated demethylation of H3K27.ConclusionsThese findings suggest a novel function of glutaminolysis in the regulation of signal transduction and metabolism reprogramming and provide further evidence for the unique role of glutaminolysis in GBM progression.

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GLUD1

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