Last update 19 Sep 2024

MDH1

Last update 19 Sep 2024

Basic Info

Synonyms

Cytosolic malate dehydrogenase, Diiodophenylpyruvate reductase, malate dehydrogenase 1

+ [3]

Introduction

Catalyzes the reduction of aromatic alpha-keto acids in the presence of NADH (PubMed:2449162, PubMed:3052244). Plays essential roles in the malate-aspartate shuttle and the tricarboxylic acid cycle, important in mitochondrial NADH supply for oxidative phosphorylation (PubMed:31538237).

Drugs associated with MDH1

FM-701

Target

MDH1 x MDH2

Mechanism

MDH1 inhibitors [+1]

Active Org.

Future Medicine Co., Ltd.

Originator Org.

Future Medicine Co., Ltd.

Active Indication

Non-Small Cell Lung Cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with MDH1

100 Translational Medicine associated with MDH1

0 Patents (Medical) associated with MDH1

550

Literatures (Medical) associated with MDH1

05 Jul 2024·Journal of Proteome Research

Identification of Candidate Protein Biomarkers Associated with Domoic Acid Toxicosis in Cerebrospinal Fluid of California Sea Lions (Zalophus californianus)

Article

Author: Bland, Alison M ; Whitmer, Emily R ; Janech, Michael G ; Field, Cara L ; Duignan, Pádraig J ; Neely, Benjamin A ; Ghosh, Gautam

Since 1998, California sea lion (Zalophus californianus) stranding events associated with domoic acid toxicosis (DAT) have consistently increased. Outside of direct measurement of domoic acid in bodily fluids at the time of stranding, there are no practical nonlethal clinical tests for the diagnosis of DAT that can be utilized in a rehabilitation facility. Proteomics analysis was conducted to discover candidate protein markers of DAT using cerebrospinal fluid from stranded California sea lions with acute DAT (n = 8), chronic DAT (n = 19), or without DAT (n = 13). A total of 2005 protein families were identified experiment-wide. A total of 83 proteins were significantly different in abundance across the three groups (adj. p < 0.05). MDH1, PLD3, ADAM22, YWHAG, VGF, and CLSTN1 could discriminate California sea lions with or without DAT (AuROC > 0.75). IGKV2D-28, PTRPF, KNG1, F2, and SNCB were able to discriminate acute DAT from chronic DAT (AuROC > 0.75). Proteins involved in alpha synuclein deposition were over-represented as classifiers of DAT, and many of these proteins have been implicated in a variety of neurodegenerative diseases. These proteins should be considered potential markers for DAT in California sea lions and should be prioritized for future validation studies as biomarkers.

01 May 2024·iScience

The acetylation of MDH1 and IDH1 is associated with energy metabolism in acute liver failure

Article

Author: Zhang, Yanqiong ; Guo, Jin ; Zhang, Danmei ; Shi, Chunxia ; Gong, Zuojiong ; Chen, Qian ; Zhang, Wenbin ; Zhang, Qingqi ; Wang, Yukun

The liver is the main organ associated with metabolism. In our previous studies, we identified that the metabolic enzymes malate dehydrogenase 1 (MDH1) and isocitrate dehydrogenase 1 (IDH1) were differentially expressed in ALF. The aim of this study was to explore the changes in the acetylation of MDH1 and IDH1 and the therapeutic effect of histone deacetylase (HDAC) inhibitor in acute liver failure (ALF). Decreased levels of many metabolites were observed in ALF patients. MDH1 and IDH1 were decreased in the livers of ALF patients. The HDAC inhibitor ACY1215 improved the expression of MDH1 and IDH1 after treatment with MDH1-siRNA and IDH1-siRNA. Transfection with mutant plasmids and adeno-associated viruses, identified MDH1 K118 acetylation and IDH1 K93 acetylation as two important sites that regulate metabolism in vitro and in vivo.

01 May 2024·Clinical and Translational Medicine

Targeting c‐Myc transactivation by LMNA inhibits tRNA processing essential for malate‐aspartate shuttle and tumour progression

Article

Author: Song, Jiyu ; Wang, Jianqun ; Cheng, Yang ; Bao, Banghe ; Yang, Chunhui ; Tong, Qiangsong ; Wang, Xiaojing ; Zheng, Liduan ; Chen, Guo ; Du, Xinyi ; Li, Dan ; Hong, Mei

AbstractBackgroundA series of studies have demonstrated the emerging involvement of transfer RNA (tRNA) processing during the progression of tumours. Nevertheless, the roles and regulating mechanisms of tRNA processing genes in neuroblastoma (NB), the prevalent malignant tumour outside the brain in children, are yet unknown.MethodsAnalysis of multi‐omics results was conducted to identify crucial regulators of downstream tRNA processing genes. Co‐immunoprecipitation and mass spectrometry methods were utilised to measure interaction between proteins. The impact of transcriptional regulators on expression of downstream genes was measured by dual‐luciferase reporter, chromatin immunoprecipitation, western blotting and real‐time quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) methods. Studies have been conducted to reveal impact and mechanisms of transcriptional regulators on biological processes of NB. Survival differences were analysed using the log‐rank test.Resultsc‐Myc was identified as a transcription factor driving tRNA processing gene expression and subsequent malate‐aspartate shuttle (MAS) in NB cells. Mechanistically, c‐Myc directly promoted the expression of glutamyl‐prolyl‐tRNA synthetase (EPRS) and leucyl‐tRNA synthetase (LARS), resulting in translational up‐regulation of glutamic‐oxaloacetic transaminase 1 (GOT1) as well as malate dehydrogenase 1 (MDH1) via inhibiting general control nonrepressed 2 or activating mechanistic target of rapamycin signalling. Meanwhile, lamin A (LMNA) inhibited c‐Myc transactivation via physical interaction, leading to suppression of MAS, aerobic glycolysis, tumourigenesis and aggressiveness. Pre‐clinically, lobeline was discovered as a LMNA‐binding compound to facilitate its interaction with c‐Myc, which inhibited aminoacyl‐tRNA synthetase expression, MAS and tumour progression of NB, as well as growth of organoid derived from c‐Myc knock‐in mice. Low levels of LMNA or elevated expression of c‐Myc, EPRS, LARS, GOT1 or MDH1 were linked to a worse outcome and a shorter survival time of clinical NB patients.ConclusionsThese results suggest that targeting c‐Myc transactivation by LMNA inhibits tRNA processing essential for MAS and tumour progression.

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MDH1

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