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Gene Review

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

Rattus norvegicus

Synonyms: Malic enzyme 1, Mod-1, Mod1, NADP-ME, NADP-dependent malic enzyme
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Disease relevance of Me1


Psychiatry related information on Me1


High impact information on Me1


Chemical compound and disease context of Me1


Biological context of Me1


Anatomical context of Me1


Associations of Me1 with chemical compounds

  • In rat liver, triiodothyronine (T3) and dietary carbohydrate induce the expression of the genes coding for malic enzyme (ME) (EC and S14 protein [17].
  • When fed to rats it induces the thermogenic enzymes mitochondrial sn-glycerol-3-phosphate dehydrogenase and cytosolic malic enzyme in their livers [22].
  • Here we show that cultured cerebellar granule neurons form releasable [(14)C]glutamate from H(14)CO(3)(-) and [1-(14)C]pyruvate via pyruvate carboxylation, probably mediated by malic enzyme [23].
  • Underlying this change is a generalized induction of the enzymes involved in lipogenesis, including glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and malic enzyme, which together serve to generate the additional NADPH required for increased fatty acid synthesis [24].
  • This report presents evidence indicating that induction of the hexose-shunt dehydrogenases involves increased enzyme synthesis secondary to elevated enzyme specific mRNA levels, as has previously been shown for malic enzyme [24].

Regulatory relationships of Me1

  • However, insulin but not IGF-I induced the expression of the lipogenic marker malic enzyme, suggesting that IGF-I but not insulin is involved in the thermogenic differentiation process of fetal brown adipocytes [25].
  • We examined the effect of clofibrate (fibrate derivative) administration for 14 days to rats on malic enzyme (as an adequate control of fibrates action) and leptin mRNAs level in the white and brown adipose tissues (WAT and BAT, respectively) [26].

Other interactions of Me1

  • As a control, we examined the effect of a high carbohydrate diet which is known to increase malic enzyme mRNA without affecting either transcriptional rate or nuclear RNA (Dozin, B., Rall, J. E., and Nikodem, V. M. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 4705-4709) [27].
  • Insulin-induced early growth response gene (Egr-1) mediates a short term repression of rat malic enzyme gene transcription [3].
  • In this study we investigated the effect of GH and IGF-I on the metabolic response of T3 in target tissues by evaluating the activity of two T3-dependent liver enzymes: mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) and cytosolic malic enzyme (ME) in rat hepatocytes in primary culture [28].
  • A single low dose of triiodothyronine induces rapid increases in cytochrome-c1 and ANT2 mRNA species which parallel changes in the activity of the hormone-responsive malic enzyme, but are earlier than other mitochondrial biogenetic events [29].
  • However, dietary levan did not affect the gene expression of hepatic malic enzyme, phosphatidate phosphohydrolase and HMG CoA reductase [30].

Analytical, diagnostic and therapeutic context of Me1


  1. Structural characterization of the rat malic enzyme gene. Morioka, H., Magnuson, M.A., Mitsuhashi, T., Song, M.K., Rall, J.E., Nikodem, V.M. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  2. Thyroid hormone-mediated transcriptional activation of the rat liver malic enzyme gene by dehydroepiandrosterone. Song, M.K., Grieco, D., Rall, J.E., Nikodem, V.M. J. Biol. Chem. (1989) [Pubmed]
  3. Insulin-induced early growth response gene (Egr-1) mediates a short term repression of rat malic enzyme gene transcription. Barroso, I., Santisteban, P. J. Biol. Chem. (1999) [Pubmed]
  4. The effect of thyroid hormone on the chromatin structure and expression of the malic enzyme gene in hepatocytes. Usala, S.J., Young, W.S., Morioka, H., Nikodem, V.M. Mol. Endocrinol. (1988) [Pubmed]
  5. Changes in the hepatic levels of messenger ribonucleic acid for malic enzyme during induction by thyroid hormone or diet. Towle, H.C., Mariash, C.N., Oppenheimer, J.H. Biochemistry (1980) [Pubmed]
  6. Malic enzyme activity in the developing rat brain in relation to thyroid status. Thakare, U.R., Shah, D.H., Vijayan, U. Int. J. Dev. Neurosci. (1989) [Pubmed]
  7. Response of hepatic mitochondrial alpha-glycerophosphate dehydrogenase and malic enzyme to constant infusions of L-triiodothyronine in rats bearing the Walker 256 carcinoma. Evidence for divergent postreceptor regulation of the thyroid hormone response. Tibaldi, J.M., Sahnoun, N., Surks, M.I. J. Clin. Invest. (1984) [Pubmed]
  8. Thyroid hormone-carbohydrate interaction in the rat: correlation between age-related reductions in the inducibility of hepatic malic enzyme by triiodo-L-thyronine and a high carbohydrate, fat-free diet. Forciea, M.A., Schwartz, H.L., Towle, H.C., Mariash, C.N., Kaiser, F.E., Oppenheimer, J.H. J. Clin. Invest. (1981) [Pubmed]
  9. Glucose and triiodothyronine both induce malic enzyme in the rat hepatocyte culture: evidence that triiodothyronine multiplies a primary glucose-generated signal. Mariash, C.N., McSwigan, C.R., Towle, H.C., Schwartz, H.L., Oppenheimer, J.H. J. Clin. Invest. (1981) [Pubmed]
  10. Synergism of thyroid hormone and high carbohydrate diet in the induction of lipogenic enzymes in the rat. Mechanisms and implications. Mariash, C.N., Kaiser, F.E., Schwartz, H.L., Towle, H.C., Oppenheimer, J.H. J. Clin. Invest. (1980) [Pubmed]
  11. Stimulation of hepatic mitochondrial alpha-glycerophosphate dehydrogenase and malic enzyme by L-triiodothyronine. Characteristics of the response with specific nuclear thyroid hormone binding sites fully saturated. Oppenheimer, J.H., Silva, E., Schwartz, H.L., Surks, M.I. J. Clin. Invest. (1977) [Pubmed]
  12. Mitochondrial malic enzymes. Mitochondrial NAD(P)+-dependent malic enzyme activity and malate-dependent pyruvate formation are progression-linked in Morris hepatomas. Sauer, L.A., Dauchy, R.T., Nagel, W.O., Morris, H.P. J. Biol. Chem. (1980) [Pubmed]
  13. Tamoxifen and ICI 182,780 interactions with thyroid hormone in the ovariectomized-thyroidectomized rat. Dipippo, V.A., Powers, C.A. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
  14. The effects of a polychlorinated biphenyl mixture (Aroclor 1254) on liver gluconeogenic enzymes of normal and alloxan-diabetic rats. Mehlman, M.A., Tobin, R.B., Friend, B., Mackerer, C.R. Toxicology (1975) [Pubmed]
  15. Tumor-induced alterations in hepatic malic enzyme and carnitine palmitoyltransferase activity. Noguchi, Y., Vydelingum, N.A., Brennan, M.F. J. Surg. Res. (1993) [Pubmed]
  16. The effects of low-dose Bay-m-1099 (Miglitol) on serum lipids and liver enzyme activity of obese and obese-diabetic corpulent rats. Tulp, O.L., Szepesi, B., Michaelis, O.E., DeBouno, J.F. Comp. Biochem. Physiol. C, Comp. Pharmacol. Toxicol. (1991) [Pubmed]
  17. Kinetics of induction by thyroid hormone of the two hepatic mRNAs coding for cytosolic malic enzyme in the hypothyroid and euthyroid states. Evidence against an obligatory role of S14 protein in malic enzyme gene expression. Strait, K.A., Kinlaw, W.B., Mariash, C.N., Oppenheimer, J.H. J. Biol. Chem. (1989) [Pubmed]
  18. Coding nucleotide sequence of rat liver malic enzyme mRNA. Magnuson, M.A., Morioka, H., Tecce, M.F., Nikodem, V.M. J. Biol. Chem. (1986) [Pubmed]
  19. Hepatic hyperplasia and cancer in rats: metabolic alterations associated with cell growth. Rao, K.N., Elm, M.S., Kelly, R.H., Chandar, N., Brady, E.P., Rao, B., Shinozuka, H., Eagon, P.K. Gastroenterology (1997) [Pubmed]
  20. Tissue-specific control of rat malic enzyme activity and messenger RNA levels by a high carbohydrate diet. Dozin, B., Rall, J.E., Nikodem, V.M. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  21. Hydroperoxide-stimulated release of calcium from rat liver and AS-30D hepatoma mitochondria. Fiskum, G., Pease, A. Cancer Res. (1986) [Pubmed]
  22. Ergosteroids: induction of thermogenic enzymes in liver of rats treated with steroids derived from dehydroepiandrosterone. Lardy, H., Partridge, B., Kneer, N., Wei, Y. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  23. Neuronal pyruvate carboxylation supports formation of transmitter glutamate. Hassel, B., Brâthe, A. J. Neurosci. (2000) [Pubmed]
  24. Changes in the rates of synthesis and messenger RNA levels of hepatic glucose-6-phosphate and 6-phosphogluconate dehydrogenases following induction by diet or thyroid hormone. Miksicek, R.J., Towle, H.C. J. Biol. Chem. (1982) [Pubmed]
  25. IGF-I induces the uncoupling protein gene expression in fetal rat brown adipocyte primary cultures: role of C/EBP transcription factors. Guerra, C., Benito, M., Fernández, M. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  26. Effect of clofibrate on malic enzyme and leptin mRNAs level in rat brown and white adipose tissue. Kochan, Z., Karbowska, J., Swierczynski, J. Horm. Metab. Res. (1999) [Pubmed]
  27. Transcriptional activation and stabilization of malic enzyme mRNA precursor by thyroid hormone. Song, M.K., Dozin, B., Grieco, D., Rall, J.E., Nikodem, V.M. J. Biol. Chem. (1988) [Pubmed]
  28. Response of triiodothyronine-dependent enzyme activities to insulin-like growth factor I and growth hormone in cultured rat hepatocytes. Pellizas, C.G., Coleoni, A.H., Cabanillas, A.M., Masini-Repiso, A.M., Costamagna, M.E. Eur. J. Endocrinol. (1996) [Pubmed]
  29. Transcript levels for nuclear-encoded mammalian mitochondrial respiratory-chain components are regulated by thyroid hormone in an uncoordinated fashion. Luciakova, K., Nelson, B.D. Eur. J. Biochem. (1992) [Pubmed]
  30. Altered mRNA expression of hepatic lipogenic enzyme and PPARalpha in rats fed dietary levan from Zymomonas mobilis. Kang, S.A., Hong, K., Jang, K.H., Kim, Y.Y., Choue, R., Lim, Y. J. Nutr. Biochem. (2006) [Pubmed]
  31. Insulin stimulation of hepatic malic enzyme activity in normal and diabetic rats controlled by different regulatory processes. Drake, R.L., Parks, W.C., Thompson, E.W. J. Biol. Chem. (1983) [Pubmed]
  32. Nicotinamide adenine dinucleotide phosphate-malic enzyme of rat liver. Purification, properties, and immunochemical studies. Li, J.J., Ross, C.R., Tepperman, H.M., Tepperman, J. J. Biol. Chem. (1975) [Pubmed]
  33. Molecular cloning of a cDNA sequence for rat malic enzyme. Direct evidence for induction in vivo of rat liver malic enzyme mRNA by thyroid hormone. Magnuson, M.A., Nikodem, V.M. J. Biol. Chem. (1983) [Pubmed]
  34. Crystallization of an NADP+-dependent malic enzyme from rat liver. Baker, P.J., Thomas, D.H., Barton, C.H., Rice, D.W., Bailey, E. J. Mol. Biol. (1987) [Pubmed]
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