MDH1
Identifiers
AliasesMDH1, HEL-S-32, MDH-s, MDHA, MGC:1375, MOR2, malate dehydrogenase 1, EIEE88, DEE88, KAR
External IDsOMIM: 154200 MGI: 97051 HomoloGene: 4324 GeneCards: MDH1
EC number1.1.1.96
Orthologs
SpeciesHumanMouse
Entrez

4190

17449

Ensembl

ENSG00000014641

ENSMUSG00000020321

UniProt

P40925

P14152

RefSeq (mRNA)

NM_005917
NM_001199111
NM_001199112
NM_001316374

NM_008618
NM_001316675

RefSeq (protein)

NP_001186040
NP_001186041
NP_001303303
NP_005908

NP_001303604
NP_032644

Location (UCSC)Chr 2: 63.59 – 63.61 MbChr 11: 21.51 – 21.52 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Malate dehydrogenase, cytoplasmic also known as malate dehydrogenase 1 is an enzyme that in humans is encoded by the MDH1 gene.[5]

Function

Malate dehydrogenase catalyzes the reversible oxidation of malate to oxaloacetate, utilizing the NAD/NADH cofactor system in the citric acid cycle. The protein encoded by this gene is localized to the cytoplasm and may play pivotal roles in the malate-aspartate shuttle that operates in the metabolic coordination between cytosol and mitochondria. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.[5]

Regulation

The acetylation of MDH1 activates its enzymatic activity and enhance intracellular levels of NADPH, which promotes adipogenic differentiation.[6]

Methylation on arginine 248 (R248) negatively regulates MDH1. Protein arginine methyltransferase 4 (PRMT4/CARM1) methylates and inhibits MDH1 by disrupting its dimerization. Arginine methylation of MDH1 represses mitochondria respiration and inhibits glutamine utilization. CARM1-mediated MDH1 methylation reduces cellular NADPH level and sensitizes cells to oxidative stress. Besides, MDH1 methylation suppresses cell growth and clonogenic activity. R248 of MDH1 is hypomethylated in pancreatic ductal adenocarcinoma.[7]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles.[§ 1]

[[File:
GlycolysisGluconeogenesis_WP534
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GlycolysisGluconeogenesis_WP534
|alt=Glycolysis and Gluconeogenesis edit]]
Glycolysis and Gluconeogenesis edit
  1. The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534".

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000014641 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000020321 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 "Entrez Gene: Malate dehydrogenase 1, NAD (soluble)".
  6. Kim EY, Kim WK, Kang HJ, Kim JH, Chung SJ, Seo YS, Park SG, Lee SC, Bae KH (Sep 2012). "Acetylation of malate dehydrogenase 1 promotes adipogenic differentiation via activating its enzymatic activity". J Lipid Res. 53 (9): 1864–76. doi:10.1194/jlr.M026567. PMC 3413227. PMID 22693256.
  7. Wang YP, Zhou W, Wang J, Huang X, Zuo Y, Wang TS, Gao X, Xu YY, Zou SW, Liu YB, Cheng JK, Lei QY (Nov 2016). "Arginine Methylation of MDH1 by CARM1 Inhibits Glutamine Metabolism and Suppresses Pancreatic Cancer". Molecular Cell. 64 (4): 673–87. doi:10.1016/j.molcel.2016.09.028. PMID 27840030.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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