MDH1

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

MDH1
Identifiers
Aliases	MDH1, HEL-S-32, MDH-s, MDHA, MGC:1375, MOR2, malate dehydrogenase 1, EIEE88, DEE88, KAR
External IDs	OMIM: 154200; MGI: 97051; HomoloGene: 4324; GeneCards: MDH1; OMA:MDH1 - orthologs
EC number	1.1.1.96
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2p15 Start 63,588,609 bp[1] End 63,607,197 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 A3.1|11 13.89 cM Start 21,506,692 bp[2] End 21,522,367 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in lateral nuclear group of thalamus right ventricle Pons middle temporal gyrus Brodmann area 10 orbitofrontal cortex left ventricle apex of heart right auricle Brodmann area 46 Top expressed in medial vestibular nucleus ventral tegmental area habenula mammillary body dorsal tegmental nucleus Epithelium of choroid plexus medial dorsal nucleus lateral hypothalamus facial motor nucleus substantia nigra More reference expression data BioGPS n/a
Gene ontology Molecular function malic enzyme activity oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor oxidoreductase activity protein binding diiodophenylpyruvate reductase activity malate dehydrogenase activity NAD binding catalytic activity L-malate dehydrogenase activity Cellular component extracellular exosome myelin sheath extracellular space cytoplasm mitochondrion cytosol Biological process gluconeogenesis NAD metabolic process carboxylic acid metabolic process tricarboxylic acid cycle oxaloacetate metabolic process malate metabolic process NADH metabolic process carbohydrate metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 11: 21.51 – 21.52 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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]}

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|alt=Glycolysis and Gluconeogenesis edit]]

Glycolysis and Gluconeogenesis edit

1. The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534".

References

1. GRCh38: Ensembl release 89: ENSG00000014641 – Ensembl, May 2017
2. 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. "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

• Fahien LA, Laboy JI, Din ZZ, Prabhakar P, Budker T, Chobanian M (Apr 1999). "Ability of cytosolic malate dehydrogenase and lactate dehydrogenase to increase the ratio of NADPH to NADH oxidation by cytosolic glycerol-3-phosphate dehydrogenase". Archives of Biochemistry and Biophysics. 364 (2): 185–94. doi:10.1006/abbi.1999.1117. PMID 10190973.
• Kaltenbach LS, Romero E, Becklin RR, Chettier R, Bell R, Phansalkar A, Strand A, Torcassi C, Savage J, Hurlburt A, Cha GH, Ukani L, Chepanoske CL, Zhen Y, Sahasrabudhe S, Olson J, Kurschner C, Ellerby LM, Peltier JM, Botas J, Hughes RE (May 2007). "Huntingtin interacting proteins are genetic modifiers of neurodegeneration". PLOS Genetics. 3 (5): e82. doi:10.1371/journal.pgen.0030082. PMC 1866352. PMID 17500595.
• Rio Frio T, Panek S, Iseli C, Di Gioia SA, Kumar A, Gal A, Rivolta C (2009). "Ultra high throughput sequencing excludes MDH1 as candidate gene for RP28-linked retinitis pigmentosa". Molecular Vision. 15: 2627–33. PMC 2790479. PMID 20011630.
• Tanaka T, Inazawa J, Nakamura Y (Feb 1996). "Molecular cloning and mapping of a human cDNA for cytosolic malate dehydrogenase (MDH1)". Genomics. 32 (1): 128–30. doi:10.1006/geno.1996.0087. PMID 8786100.
• Friedrich CA, Ferrell RE, Siciliano MJ, Kitto GB (Jan 1988). "Biochemical and genetic identity of alpha-keto acid reductase and cytoplasmic malate dehydrogenase from human erythrocytes". Annals of Human Genetics. 52 (Pt 1): 25–37. doi:10.1111/j.1469-1809.1988.tb01075.x. PMID 3052244. S2CID 41389918.
• Chapman AD, Cortés A, Dafforn TR, Clarke AR, Brady RL (Jan 1999). "Structural basis of substrate specificity in malate dehydrogenases: crystal structure of a ternary complex of porcine cytoplasmic malate dehydrogenase, alpha-ketomalonate and tetrahydoNAD". Journal of Molecular Biology. 285 (2): 703–12. doi:10.1006/jmbi.1998.2357. PMID 10075524.
• Martins-de-Souza D, Gattaz WF, Schmitt A, Maccarrone G, Hunyadi-Gulyás E, Eberlin MN, Souza GH, Marangoni S, Novello JC, Turck CW, Dias-Neto E (Jul 2009). "Proteomic analysis of dorsolateral prefrontal cortex indicates the involvement of cytoskeleton, oligodendrocyte, energy metabolism and new potential markers in schizophrenia". Journal of Psychiatric Research. 43 (11): 978–86. doi:10.1016/j.jpsychires.2008.11.006. PMID 19110265.
• Corbett JM, Wheeler CH, Baker CS, Yacoub MH, Dunn MJ (Nov 1994). "The human myocardial two-dimensional gel protein database: update 1994". Electrophoresis. 15 (11): 1459–65. doi:10.1002/elps.11501501209. PMID 7895732. S2CID 33359306.

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