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Gene Review

ME1  -  malic enzyme 1, NADP(+)-dependent, cytosolic

Homo sapiens

Synonyms: HUMNDME, MES, Malic enzyme 1, NADP-ME, NADP-dependent malic enzyme
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Disease relevance of ME1


Psychiatry related information on ME1

  • Maximal seizures were induced by corneal electroshock (MES), and phenytoin was injected into the ventral lymph sac [6].
  • Further, those patients with the highest MES/NEO ratios had the lowest overall measures of cognitive function (Folstein Mini-Mental Status Examination: r = -.75, P < .02, 1-tail; Mattis Dementia Rating Scale: r = -0.655, P = .028, 1-tail) scores [7].

High impact information on ME1

  • We have followed, in situ, the accumulation of malic enzyme (ME), phosphoenolpyruvate carboxylase (PEPCase), and ribulose bisphosphate carboxylase (RuBPCase) mRNAs in developing leaves of both normal and mutant argentia (ar) maize [8].
  • Experiments with hybrid exons created from the HLA-B27 and HLA-A2 genes yielded results consistent with the mapping of the ME1 epitope to the B27 alpha 1 domain [9].
  • The eggs of the surf clam Spisula solidissima were artificially activated, homogenized at various times in cold 0.5 M MES buffer, 1mM EGTA at pH 6.5, and microtubule polymerization was induced by raising the temperature to 28 degrees C. In homogenates of unactivated eggs few microtubules form and no asters are observed [10].
  • The phospholamban, malic enzyme 1-soluble, and laminin-alpha4 genes were excluded as candidate genes, using single-strand conformation polymorphism or linkage analysis [11].
  • The crystal structure of human mitochondrial NAD(P)+-dependent malic enzyme in a quaternary complex with NAD+, Mn++ and oxalate has been determined at 2.2 A resolution [12].

Chemical compound and disease context of ME1


Biological context of ME1

  • Since the assignment of F13A to the short arm of chromosome 6 was recently confirmed, the locus for ME2 can be added to this linkage group [16].
  • 3. Segregation of human enzymes in human--mouse and human--hamster somatic cell hybrids confirms the synteny of MES and PGM3 [17].
  • In contrast, decarboxylation catalysed by mitochondrial malic enzyme, was unaffected by the substrate [18].
  • 1. The human brain cytosolic malic enzyme displayed a hyperbolic substrate saturation kinetics and no sigmoidicity was detected even at high pH and low malate concentrations [18].
  • One may speculate that in vivo the reaction catalysed by cytosolic malic enzyme supplies dicarboxylic acids (anaplerotic function) for the formation of neurotransmitters, while the mitochondrial enzyme regulates the flux rate via Krebs cycle by disposition of the tricarboxylic acid cycle intermediates (cataplerotic function) [18].

Anatomical context of ME1


Associations of ME1 with chemical compounds


Physical interactions of ME1

  • Malic enzyme of pigeon liver binds NADPH at four equivalent enzyme sites and binds Mn2+ and malate each at two sets of "tight" and "weak" sites with negative cooperativity [Pry, T. A., & Hsu, R. Y. (1980) Biochemistry 19, 951-962] [23].

Regulatory relationships of ME1

  • These results indicate that PBX-MEIS1 complexes interact with nuclear T3 receptors to enhance T3 regulation of malic enzyme transcription in hepatocytes [24].
  • Glucagon rapidly and specifically inhibited synthesis of malic enzyme in preinduced cells, suggesting an action at the level of translation or cytoplasmic messenger RNA processing [25].
  • These findings suggest that cell-specific factors control the ability of TR alpha to regulate the malic enzyme gene [26].

Other interactions of ME1


Analytical, diagnostic and therapeutic context of ME1

  • This work reports the structure of a cDNA (ME) encoding a human malic enzyme (ME) (malate NADP oxidoreductase, EC elucidated by joining several overlapping fragments amplified by PCR from human hepatic cDNA or from cDNA libraries [31].
  • Amino acid composition and western-blot analysis further suggested a structural similarity between ME1 and ME2 [3].
  • The two RIPs, named ME1 and ME2, were purified to homogeneity by ammonium sulfate precipitation, cation-exchange perfusion chromatography, and C4 reverse-phase chromatography [3].
  • Our results with ME1, the first monoclonal antibody that recognizes malignant mesothelial cells, provides a basis for using this reagent in the differential diagnosis of tumors of the pleura and peritoneum [32].
  • Out of the 32 residues comprising the transmembrane helix of GpA, five amino acids were mutated; the resulting protein, ME1, has been characterized in dodecyl phosphocholin (DPC) micelles by UV-vis, CD spectroscopy, gel electrophoresis, and analytical ultracentrifugation [33].


  1. Characterization of cytosolic malic enzyme in human tumor cells. Loeber, G., Dworkin, M.B., Infante, A., Ahorn, H. FEBS Lett. (1994) [Pubmed]
  2. Nonidentity of the cDNA sequence of human breast cancer cell malic enzyme to that from the normal human cell. Chou, W.Y., Huang, S.M., Chang, G.G. J. Protein Chem. (1996) [Pubmed]
  3. Characterization of two novel type I ribosome-inactivating proteins from the storage roots of the andean crop Mirabilis expansa. Vivanco, J.M., Savary, B.J., Flores, H.E. Plant Physiol. (1999) [Pubmed]
  4. Monoclonal antibodies against mesothelial membrane antigen discriminate between malignant mesothelioma and lung adenocarcinoma. Stahel, R.A., O'Hara, C.J., Waibel, R., Martin, A. Int. J. Cancer (1988) [Pubmed]
  5. Formal genetics of the HL-A region. Dausset, J., Degos, L., Fellous, M., Legrand, L. Genetics (1975) [Pubmed]
  6. Dose-response analysis of phenytoin on electrically induced seizures and spontaneous activity of cerebellar purkinje cells in the frog. Johnson, S.W., Riker, W.K. Epilepsia (1982) [Pubmed]
  7. The ratio of mesial to neocortical temporal lobe blood flow as a predictor of dementia. Cohen, R.M., Andreason, P.J., Sunderland, T. Journal of the American Geriatrics Society. (1997) [Pubmed]
  8. Cellular pattern of photosynthetic gene expression in developing maize leaves. Langdale, J.A., Rothermel, B.A., Nelson, T. Genes Dev. (1988) [Pubmed]
  9. In vitro mutagenesis of HLA-B27. Substitution of an unpaired cysteine residue in the alpha 1 domain causes loss of antibody-defined epitopes. Taurog, J.D., el-Zaatari, F.A. J. Clin. Invest. (1988) [Pubmed]
  10. In vitro polymerization of microtubules into asters and spindles in homogenates of surf clam eggs. Weisenberg, R.C., Rosenfeld, A.C. J. Cell Biol. (1975) [Pubmed]
  11. A new locus for autosomal dominant dilated cardiomyopathy identified on chromosome 6q12-q16. Sylvius, N., Tesson, F., Gayet, C., Charron, P., Bénaïche, A., Peuchmaurd, M., Duboscq-Bidot, L., Feingold, J., Beckmann, J.S., Bouchier, C., Komajda, M. Am. J. Hum. Genet. (2001) [Pubmed]
  12. Structure of a closed form of human malic enzyme and implications for catalytic mechanism. Yang, Z., Floyd, D.L., Loeber, G., Tong, L. Nat. Struct. Biol. (2000) [Pubmed]
  13. Kinetics and regulation of hepatoma mitochondrial NAD(P) malic enzyme. Teller, J.K., Fahien, L.A., Davis, J.W. J. Biol. Chem. (1992) [Pubmed]
  14. Cell-specific regulation of transcription of the malic enzyme gene: characterization of cis-acting elements that modulate nuclear T3 receptor activity. Fang, X., Hillgartner, F.B. Arch. Biochem. Biophys. (1998) [Pubmed]
  15. Crystallization and preliminary X-ray analysis of cellobiose phosphorylase from Cellvibrio gilvus. Hidaka, M., Kitaoka, M., Hayashi, K., Wakagi, T., Shoun, H., Fushinobu, S. Acta Crystallogr. D Biol. Crystallogr. (2004) [Pubmed]
  16. Linkage between the loci for mitochondrial malic enzyme (ME2) and coagulation factor XIIIA subunit (F13A). Kömpf, J., Schunter, F., Wernet, P., Ritter, H. Hum. Genet. (1985) [Pubmed]
  17. Sub-unit structure of soluble and mitochondrial malic enzyme: demonstration of human mitochondrial enzyme in human-mouse hybrids. Povey, S., Wilson, D.E., Harris, H., Gormley, I.P., Perry, P., Buckton, K.E. Ann. Hum. Genet. (1975) [Pubmed]
  18. Different regulatory properties of the cytosolic and mitochondrial forms of malic enzyme isolated from human brain. Bukato, G., Kochan, Z., Swierczyński, J. Int. J. Biochem. Cell Biol. (1995) [Pubmed]
  19. A population study of leukocyte enzymes (GOT2, ME2 and PGM3) in Galicia (NW Spain). Llano, C., Caeiro, J.L., Boán, F. Hum. Hered. (1990) [Pubmed]
  20. Purification and properties of cytosolic and mitochondrial malic enzyme isolated from human brain. Bukato, G., Kochan, Z., Swierczyński, J. Int. J. Biochem. Cell Biol. (1995) [Pubmed]
  21. Purification and properties of cytosolic malic enzyme from human skeletal muscle. Taroni, F., Di Donato, S. Int. J. Biochem. (1988) [Pubmed]
  22. Molecular cloning and functional characterization of the human cytosolic malic enzyme promoter: thyroid hormone responsiveness. González-Manchón, C., Butta, N., Ferrer, M., Ayuso, M.S., Parrilla, R. DNA Cell Biol. (1997) [Pubmed]
  23. Kinetics of dissociation of reduced nicotinamide adenine dinucleotide phosphate from its complexes with malic enzyme in relation to substrate inhibition and half-of-the-sites reactivity. Dalziel, K., Hsu, R.Y., Matthews, B., Soulié, J.M. Biochemistry (1983) [Pubmed]
  24. The homeodomain proteins PBX and MEIS1 are accessory factors that enhance thyroid hormone regulation of the malic enzyme gene in hepatocytes. Wang, Y., Yin, L., Hillgartner, F.B. J. Biol. Chem. (2001) [Pubmed]
  25. Regulation of malic enzyme synthesis by insulin triiodothyronine, and glucagon in liver cells in culture. Goodridge, A.G., Adelman, T.G. J. Biol. Chem. (1976) [Pubmed]
  26. Overexpression of the alpha-thyroid hormone receptor in avian cell lines. Effects on expression of the malic enzyme gene are selective and cell-specific. Hillgartner, F.B., Chen, W., Goodridge, A.G. J. Biol. Chem. (1992) [Pubmed]
  27. Assignment of the major histocompatibility complex to a region of the short arm of human chromosome 6. Francke, U., Pellegrino, M.A. Proc. Natl. Acad. Sci. U.S.A. (1977) [Pubmed]
  28. Respiratory properties and malate metabolism in Percoll-purified mitochondria isolated from pineapple, Ananas comosus (L.) Merr. cv. smooth cayenne. Hong, H.T., Nose, A., Agarie, S. J. Exp. Bot. (2004) [Pubmed]
  29. A bienzyme electrode for L-malate based on a novel and general design. Gajovic, N., Warsinke, A., Scheller, F.W. J. Biotechnol. (1998) [Pubmed]
  30. Phenotypic and functional characteristics of porcine peritoneal mesothelial cells. Ohan, J., Gilbert, M.A., Brouland, J.P., Rougier, J.P., Trugnan, G., Wassef, M., Leseche, G., Drouet, L. In Vitro Cell. Dev. Biol. Anim. (1999) [Pubmed]
  31. Cloning, sequencing and functional expression of a cDNA encoding a NADP-dependent malic enzyme from human liver. González-Manchón, C., Ferrer, M., Ayuso, M.S., Parrilla, R. Gene (1995) [Pubmed]
  32. ME1. A monoclonal antibody that distinguishes epithelial-type malignant mesothelioma from pulmonary adenocarcinoma and extrapulmonary malignancies. O'Hara, C.J., Corson, J.M., Pinkus, G.S., Stahel, R.A. Am. J. Pathol. (1990) [Pubmed]
  33. Design of a functional membrane protein by engineering a heme-binding site in glycophorin A. Cordova, J.M., Noack, P.L., Hilcove, S.A., Lear, J.D., Ghirlanda, G. J. Am. Chem. Soc. (2007) [Pubmed]
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