MDH1
| MDH1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Malate dehydrogenase, cytoplasmic also known as malate dehydrogenase 1 is an enzyme that in humans is encoded by the MDH1 gene.[5]
Function
[edit]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
[edit]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
[edit]Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
- ^ The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534".
References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000014641 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020321 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "Entrez Gene: Malate dehydrogenase 1, NAD (soluble)".
- ^ 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.
- ^ 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
[edit]- 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.
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