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Gene Review

Me1  -  malic enzyme 1, NADP(+)-dependent, cytosolic

Mus musculus

Synonyms: D9Ertd267e, Malic enzyme 1, Mdh-1, Mod-1, Mod1, ...
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Disease relevance of Mod1

  • A recombinant phage with a 2-kb insert was isolated by screening with wild type malic enzyme cDNA probes [1].
  • Identification and properties of the nicotinamide adenine dinucleotide (phosphate)+-dependent malic enzyme in mouse ascites tumor mitochondria [2].
  • Expression of the processed protein in E. coli yielded an enzyme with the same kinetic and allosteric properties as malic enzyme purified from human cells [3].
  • We postulate that an active malic enzyme may suppress the synthesis of aspartate in hepatoma cells, but further evidence is needed to confirm this assumption [4].
  • Quantitative reverse transcription-PCR analysis revealed that lipid metabolism-related genes, including carnitine palmitoyltransferase (CPT) I, liver fatty acid binding protein, pyruvate dehydrogenase kinase-4, and NADP(+)-dependent cytosolic malic enzyme, were upregulated by HF feeding in both strains of mice [5].

High impact information on Mod1

  • During the adipose differentiation of 3T3-F442A cells, there is an increase in the synthesis of numerous proteins, including the lipogenic enzymes glycerophosphate dehydrogenase, fatty acid synthetase and malic enzyme [6].
  • Effect of gene dosage on expression of mitochondrial malic enzyme activity in the mouse [7].
  • A regulatory gene (Mdr-1), closely linked to Mod-2 on chromosome 7, determines the rate of mitochondrial malic enzyme synthesis in brain [8].
  • Mouse mitochondrial malic enzyme [L-malate:NADP+ oxidoreductase (oxaloacetate-decarboxylating), EC] is a tetrameric protein [8].
  • The late replication data are consistent with the measurements of levels of mitochondrial malic enzyme (MOD-2, whose locus is on the autosomal segment) activity in these mice [Eicher E. & Coleman, D. (1977) Genetics 85, 647-658] [9].

Chemical compound and disease context of Mod1


Biological context of Mod1


Anatomical context of Mod1


Associations of Mod1 with chemical compounds

  • In a previous study [Bernstine, E.G. (1979) J. Biol. Chem. 254, 83-87] it was shown that inbred strains of mice fall into two classes based on the specific activity of mitochondrial malic enzyme [L-malate:NADP+ oxidoreductase (oxaloacetate-decarboxylating), EC] in brain [16].
  • Many murine cells express two mRNAs with markedly different sizes (2.0 and 3.1 kilobases (kb)) that hybridize with cDNA probes for cytosolic malic enzyme ((S)-malate NADP+ oxidoreductase (oxaloacetate-decarboxylating, EC [13].
  • Increases were found in hexokinase and enolase with an upward trend in pyruvate kinase in the ob/ob mouse kidney; a significant decline in malic enzyme was also seen [17].
  • The activities of lipogenic enzymes including malic enzyme, glucose-6-phosphate dehydrogenase, and 6-phosphoglucuronic acid dehydrogenase in chronic alcohol-treated rats are significantly decreased by GF-AS [18].
  • The antigenic peptide is presented by HLA-A2 molecules and encoded by a mutated sequence in the gene coding for malic enzyme, an essential enzyme that converts malate to pyruvate [15].

Physical interactions of Mod1


Regulatory relationships of Mod1


Other interactions of Mod1

  • This panel allowed us to map five microsatellite loci as well as d and Mod-1 with respect to tk [23].
  • By observing the segregation of alleles at the Mod-1 (cytoplasmic malic enzyme) locus, which is known to lie distal to these three markers, it was possible to show that Lap-1 is at the centromeric end of this gene group [24].
  • Three loci (Es-3, Hbb and Mod-1) had low levels of polymorphism in 1981 and had become monomorphic by 1990 [25].
  • Linked to Gst-2 on mouse chromosome 9 are two enzyme-encoding loci, Pgm-3 and Mod-1 [26].
  • The strain distribution pattern for this locus, supernatant malic enzyme, and transferrin also on Chromosome 9, are given for 67 inbred strains [27].

Analytical, diagnostic and therapeutic context of Mod1


  1. The molecular basis for a cytosolic malic enzyme null mutation. Malic enzyme mRNA from MOD-1 null mice contains an internal in-frame duplication that extends the coding sequence by 522 nucleotides. Brown, M.L., Wise, L.S., Rubin, C.S. J. Biol. Chem. (1988) [Pubmed]
  2. Identification and properties of the nicotinamide adenine dinucleotide (phosphate)+-dependent malic enzyme in mouse ascites tumor mitochondria. Sauer, L.A., Dauchy, R.T. Cancer Res. (1978) [Pubmed]
  3. Human NAD(+)-dependent mitochondrial malic enzyme. cDNA cloning, primary structure, and expression in Escherichia coli. Loeber, G., Infante, A.A., Maurer-Fogy, I., Krystek, E., Dworkin, M.B. J. Biol. Chem. (1991) [Pubmed]
  4. Control and function of the transamination pathways of glutamine oxidation in tumour cells. Kovacević, Z., Brkljac, O., Bajin, K. Biochem. J. (1991) [Pubmed]
  5. Differential regulation of intestinal lipid metabolism-related genes in obesity-resistant A/J vs. obesity-prone C57BL/6J mice. Kondo, H., Minegishi, Y., Komine, Y., Mori, T., Matsumoto, I., Abe, K., Tokimitsu, I., Hase, T., Murase, T. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  6. Cyclic AMP-mediated control of lipogenic enzyme synthesis during adipose differentiation of 3T3 cells. Spiegelman, B.M., Green, H. Cell (1981) [Pubmed]
  7. Effect of gene dosage on expression of mitochondrial malic enzyme activity in the mouse. Bernstine, E.G., Russell, L.B., Cain, C.S. Nature (1978) [Pubmed]
  8. A cis-active regulatory gene in the mouse: direct demonstration of cis-active control of the rate of enzyme subunit synthesis. Bernstine, E.G., Koh, C. Proc. Natl. Acad. Sci. U.S.A. (1980) [Pubmed]
  9. Late replication in an X-autosome translocation in the mouse: correlation with genetic inactivation and evidence for selective effects during embryogenesis. Disteche, C.M., Eicher, E.M., Latt, S.A. Proc. Natl. Acad. Sci. U.S.A. (1979) [Pubmed]
  10. Adipose gene expression response of lean and obese mice to short-term dietary restriction. van Schothorst, E.M., Keijer, J., Pennings, J.L., Opperhuizen, A., van den Brom, C.E., Kohl, T., Franssen-van Hal, N.L., Hoebee, B. Obesity (Silver Spring, Md.) (2006) [Pubmed]
  11. A malic enzyme probe detects cross-hybridizing sequences closely linked to loci encoding other metabolic enzymes. Cobb, R.R., Rinchik, E., Barnett, L.B., Burkhart, J.G., Lewis, S.E. Genomics (1992) [Pubmed]
  12. Chromosome localization of the loci for PEPA, PEPB, PEPS, IDH1, GSR, MPI, PGM1, NP, SOD1, and ME1 in the common shrew (Sorex araneus). Matyakhina, L.D., Colonin, M.G., Pack, S.D., Borodin, P.M., Searle, J.B., Serov, O.L. Mamm. Genome (1996) [Pubmed]
  13. Structure and expression of murine malic enzyme mRNA. Differentiation-dependent accumulation of two forms of malic enzyme mRNA in 3T3-L1 cells. Bagchi, S., Wise, L.S., Brown, M.L., Bregman, D., Sul, H.S., Rubin, C.S. J. Biol. Chem. (1987) [Pubmed]
  14. Cloning of cDNA sequences for murine malic enzyme and the identification of aberrantly large malic enzyme mRNA in MOD-1 null mice. Sul, H.S., Wise, L.S., Brown, M.L., Rubin, C.S. J. Biol. Chem. (1984) [Pubmed]
  15. High frequency of cytolytic T lymphocytes directed against a tumor-specific mutated antigen detectable with HLA tetramers in the blood of a lung carcinoma patient with long survival. Karanikas, V., Colau, D., Baurain, J.F., Chiari, R., Thonnard, J., Gutierrez-Roelens, I., Goffinet, C., Van Schaftingen, E.V., Weynants, P., Boon, T., Coulie, P.G. Cancer Res. (2001) [Pubmed]
  16. Regulation of mitochondrial malic enzyme synthesis in mouse brain. Bernstine, E.G., Koh, C., Lovelace, C.C. Proc. Natl. Acad. Sci. U.S.A. (1979) [Pubmed]
  17. Regulation of pathways of glucose metabolism in the kidney. The activity of the pentose phosphate pathway, glycolytic route and the regulation of phosphofructokinase in the kidney of lean and genetically obese (ob/ob) mice; comparison with effects of diabetes. Sochor, M., Kunjara, S., McLean, P. Horm. Metab. Res. (1988) [Pubmed]
  18. Glycoprotein isolated from Acanthopanax senticosus protects against hepatotoxicity induced by acute and chronic alcohol treatment. Choi, J.S., Yoon, T.J., Kang, K.R., Lee, K.H., Kim, W.H., Suh, Y.H., Song, J., Jung, M.H. Biol. Pharm. Bull. (2006) [Pubmed]
  19. Survey of normal appearing mouse strain which lacks malic enzyme and Nad+-linked glycerol phosphate dehydrogenase: normal pancreatic beta cell function, but abnormal metabolite pattern in skeletal muscle. MacDonald, M.J., Marshall, L.K. Mol. Cell. Biochem. (2001) [Pubmed]
  20. Genetic regulation of malic enzyme activity in the mouse. Coleman, D.L., Kuzava, J.E. J. Biol. Chem. (1991) [Pubmed]
  21. Effects of antiretroviral drug combinations on the differentiation of adipocytes. Roche, R., Poizot-Martin, I., Yazidi, C.M., Compe, E., Gastaut, J.A., Torresani, J., Planells, R. AIDS (2002) [Pubmed]
  22. Hepatic drug metabolism and the activities of NADPH generating enzymes and glucose-6-phosphatase in phenobarbital treated genetically obese (ob/ob) mice. Stengard, J.H., Saarni, H.U., Karvonen, R.I., Lahtela, J.T., Kärki, N.T., Stenbäck, F., Sotaniemi, E.A. Biomed. Pharmacother. (1987) [Pubmed]
  23. The genetic map around the tail kinks (tk) locus on mouse chromosome 9. Imai, K., Nass, S.J., Olowson, M., Balling, R. Mamm. Genome (1993) [Pubmed]
  24. Location of the gene for theta antigen in the mouse. III. The position of Thy-1 relative to Lap-1 and Mpi-1. Douglas, T.C., Dawson, P.E. J. Hered. (1979) [Pubmed]
  25. Electrophoretic variation in multiple recessive tester, T, stock mice. Peters, J., Lewis, S.E. Mutat. Res. (1991) [Pubmed]
  26. Mapping of class alpha glutathione S-transferase 2 (GST-2) genes to the vicinity of the d locus on mouse chromosome 9. Kasahara, M., Matsumura, E., Webb, G., Board, P.G., Figueroa, F., Klein, J. Genomics (1990) [Pubmed]
  27. A serum protein polymorphism determinant on chromosome 9 of Mus musculus. Eicher, E.M., Taylor, B.A., Leighton, S.C., Womack, J.E. Mol. Gen. Genet. (1980) [Pubmed]
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