Malic Enzyme Gene Research Articles

Hormonal regulation of lipogenic enzymes in chick embryo hepatocytes in culture. Thyroid hormone and glucagon regulate malic enzyme mRNA level at post-transcriptional steps.

Mechanisms involved in stimulation of the synthesis of malic enzyme by insulin and triiodothyronine and in inhibition of synthesis by glucagon have been investigated by assessing levels and rates of synthesis of malic enzyme mRNA in chick embryo hepatocytes in culture. Insulin alone had no effect on the level of malic enzyme mRNA, whereas triiodothyronine by itself caused a 7-fold increase. Insulin plus triiodothyronine caused an 11-fold increase. Glucagon caused a 93% decrease in the accumulation of malic enzyme mRNA caused by insulin plus triiodothyronine. Although the relative changes in mRNA level are smaller in magnitude, they are qualitatively similar to the effects of these hormones on synthesis of malic enzyme, suggesting that control is exerted primarily at pretranslational steps. After addition of triiodothyronine, malic enzyme mRNA accumulated with sigmoidal kinetics, approaching a new steady state at 36-48 h after adding hormone. Puromycin, an inhibitor of protein synthesis, blocked the effect of triiodothyronine if added 30 min prior to the hormone and inhibited further accumulation of malic enzyme mRNA if added 24 h after triiodothyronine. However, puromycin had no effect on the level of beta-tubulin mRNA (t1/2 = 3-5 h), suggesting that the effect of triiodothyronine on malic enzyme mRNA required synthesis of a peptide. Triiodothyronine increased transcription of the malic enzyme gene by 2-fold and level of its mRNA by 11-14-fold, indicating regulation is primarily at a post-transcriptional step. Glucagon caused malic enzyme mRNA to decay with a half-life of 1.5 h, whereas alpha-amanitin or actinomycin D, inhibitors of transcription, caused the mRNA to decay with a half-life of 8-11 h. The effect of glucagon was entirely post-transcriptional because the hormone had no effect on transcription. Taken together, these results suggest a model in which triiodothyronine regulates production of a peptide that stabilizes malic enzyme transcripts in the cytoplasm and/or nucleus. Glucagon may inhibit activity of the peptide induced by triiodothyronine.

Thyroid hormone regulation of malic enzyme synthesis. Dual tissue-specific control.

The regulatory mechanism(s) involved in the tissue-specific induction of cytosolic malic enzyme (EC 1.1.1.40) by triiodothyronine (T3) have been investigated in rat liver and heart. In these two tissues, cellular malic enzyme mRNA accumulates to different extents in response to hormonal stimulation (11-16- and 3-4-fold above the respective basal levels) (Dozin, B., Magnuson, M. A., and Nikodem, V. M. (1985) Biochemistry 24, 5581-5586). To gain further insight into this pretranslational control, nuclear in vitro run-off transcription assays were performed and correlated with the levels of malic enzyme RNA sequences in cytoplasm. The data demonstrate that the rate of transcription of the malic enzyme gene is stimulated by T3 to similar extents in liver and heart (3-4-fold above the basal activity). In liver, T3 also promotes an additional increase in cellular malic enzyme mRNA. This additional effect could be due to a tissue-specific change in the rate of degradation of cytoplasmic mRNA or to an effect on malic enzyme mRNA in the nucleus.

Tissue-specific control of rat malic enzyme activity and messenger RNA levels by a high carbohydrate diet.

In euthyroid rats fed a high carbohydrate fat-free diet for 10 days, the mass of cellular malic enzyme mRNA in liver is increased 7- to 8-fold above the basal level. Malic enzyme activity is stimulated to the same extent. This effect does not result from an increase either in the transcriptional activity of the malic enzyme gene, as determined by nuclear run-off transcription assay, or in the content of intranuclear malic enzyme RNA sequences. Mathematical modeling shows that this increase in cytoplasmic mRNA is compatible with retarded degradation of cytoplasmic mRNA. Regulation of malic enzyme by carbohydrates is liver-specific, since no response is observed in the following nonhepatic tissues: brain, heart, spleen, kidney, testis, and lung. Furthermore, the amplitude of the response in liver depends on the thyroid state of the animals, being lower (by a factor of approximately 4) in hypothyroidism and higher (12- to 15-fold) when normal animals are injected simultaneously with a daily dose of 15 micrograms of triiodothyronine per 100 g of body weight for 10 days. Since thyroid hormones regulate liver malic enzyme synthesis predominantly at the nuclear level and carbohydrates at the cytoplasmic level, the additive effect of triiodothyronine and a high carbohydrate diet on the activity of malic enzyme is readily explicable.

Nutritional regulation of the synthesis and degradation of malic enzyme messenger RNA in duck liver.

The amount of malic enzyme mRNA in total liver RNA increased rapidly when starved ducklings were fed a high-carbohydrate mash diet, reaching 15 times the initial level at 9 h and an apparent steady state, about 20 times the initial level, at 24 h. Based on the kinetics of accumulation, malic enzyme mRNA had a half-life of 3-5 h in the livers of fed ducklings. When fed ducklings were starved, malic enzyme mRNA decreased with a half-life of about 1 h. Feeding, therefore, may have inhibited the degradation of malic enzyme mRNA, but not sufficiently to account for the 20-fold increase in mRNA level. The level of malic enzyme sequences in nuclear RNA increased severalfold when starved ducklings were fed, consistent with a stimulation of transcription. The rate of transcription of the malic enzyme gene, as measured in isolated nuclei, increased 3-5-fold when starved ducklings were refed. Starvation of fed animals caused a 55-65% inhibition of the transcription of the malic enzyme gene. Synthesis of albumin mRNA was little affected by refeeding or starvation, indicating that the observed effects on synthesis of malic enzyme mRNA were selective. We conclude that both increased transcription and decreased degradation contribute to the 20-fold increase in malic enzyme mRNA caused by feeding starved ducklings.

Genetic and cytogenetic studies of malic enzyme in Drosophila melanogaster.

The genetic and cytogenetic locations of the structural gene (Men) for malic enzyme have been determined. Men maps genetically between kar and ry at 51.73 +/- 0.02. Cytogenetically, Men probably lies in the proximal edge of 87D1,2, based on the results of mapping utilizing a number of deficiencies with breakpoints in that region. A number of null alleles have been recovered; heterozygotes for these nulls and a Men deficiency are both viable and fertile. These findings are related to the one band, one functional unit model of salivary gland chromosome structure.

Regulation of mitochondrial malic enzyme synthesis in mouse brain.

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 1.1.1.40] in brain. In this report we demonstrate differences between high- and low-activity strains in the development of enzyme activity levels in adult mice and show that the rate of enzyme synthesis quantitatively accounts for the inherited level of the brain enzyme. Genetic analysis has established that the locus controlling the amount of enzyme in brain (Mdr-1) is located on chromosome 7. Its linkage to Hbb and c places it in the same region of the chromosome as Mod-2, the structural gene for mitochondrial malic enzyme. By making use of deletions and a duplication that include Mod-2, evidence for cis action of Mdr-1 was obtained.

Effect of gene dosage on expression of mitochondrial malic enzyme activity in the mouse.

THE region of chromosome 7 in Mus musculus in which the albino (c) locus is located is of special interest because it is involved in deficiencies1–6, a duplication7,8, and X-autosome translocations9–11. The structural gene (Mod-2) for mitochondrial malic enzyme (MOD-2) maps about 1 centimorgan (ref. 12) to the distal side of c, and has been shown by genetic experiments4,5 to be deleted in certain lethal albino mutations. Over 30 independently isolated homozygous lethal c-locus mutations have been recovered and characterised at Oak Ridge. In this report we have compared the level of MOD-2 expression in animals heterozygous for lethal c-locus mutations (cch/c*) with that of their cch/cch littermates in order to clarify the precise quantitative effect of gene dosage on the expression of enzyme activity in this system. We have shown that enzyme activity is linearly related to gene dosage in both heart and kidney. The data demonstrate that four out of seven complementation groups of c* mutations are most simply explained as deficiencies that include Mod-2.

Selective alterations in hepatic enzyme response after reduction of nuclear triiodothyronine receptor sites by partial hepatectomy and starvation

Partial hepatectomy results in a decrease in the nuclear triiodothyronine binding capacity of rat liver. Although we confirmed reports that starvation causes a reduction in binding capacity, starvation alone did not fully account for the decrease after hepatectomy. Reduction in nuclear binding sites both by hepatectomy and starvation failed to impair the response to triiodothyronine administration as measured by an increase in the enzyme activity of mitochondrial α-glycerophosphate dehydrogenase, but significantly blocked the triiodothyronine response as measured by cytosolic malic enzyme. These findings indicate that triiodothyronine response is influenced by currently undefined metabolic factors and raises the possibility that such factors cause a selective decrease in receptors associated with the gene for malic enzyme.

Mechanisms and regulation of biosynthesis of saturated fatty acids.

Mechanisms and regulation of biosynthesis of saturated fatty acids.

Chromosome assignments of genes in man using mouse-human somatic cell hybrids: mitochondrial superoxide dismutase (indophenol oxidase-B, tetrameric) to chromosome 6.

Evidence from mouse/human somatic cell hybrids is presented for the synteny of the genes for indophenol oxidase-B (tetrameric) and cytoplasmic malic enzyme (EC 1.1.1.40). Assignment of these two genes to chromosome 6 is further confirmed. The identification of indophenol oxidase-B (tetrameric) as mitochondrial superoxide dismutase is discussed.

A possible mechanism for the transfer of cytosol-generated NADPH to the mitochondrial mixed-function oxidases in bovine adrenal cortex: A malate shuttle

The promoters of many genes contain C-rich polypyrimidine/polypurine (PPY/PPU) sequences that are important for gene expression. The promoter of the chicken malic enzyme gene contains a long PPY/PPU tract that can act as an alternative promoter. This tract can be separated functionally into a C-rich and (CT)7sequences. The (CT)7region together with some 3′ nucleotides is essential for function of the alternative transcription start site and the C-rich sequence as a regulatory element. In constructs that contained the PPY/PPU tract or the −147/+31-bp promoter of the malic enzyme gene connected to a reporter gene, deletion of the C-rich region increased gene expression. In constructs containing 5.8-kb 5′-flanking DNA of the gene, deletion of the same C-rich region decreased expression of the reporter gene. Positive function of the C-rich sequence required two upstream DNA regions, −237 to −147 bp and −3474 to −2715 bp. To understand the mechanism(s) by which the same sequence exerts different effects, we examined the transcription start sites in the construct where the C-rich region was deleted. We directly visualized transcription start sites by performing 5′-rapid amplification of cDNA ends and a subsequent primer extension on a single-stranded template. Deletion of the C-rich region from constructs containing 5.8 kb of 5′-flanking DNA almost completely abolished transcription initiation from the PPY/PPU promoter and reduced transcription from the major endogenous start site. DEAE fractionation of hepatic nuclear extract revealed more than 10 proteins that bound specifically to C-rich DNA. These results suggest that interactions between upstream DNA elements and the C-rich sequence and the selective use of DNA-binding activities may bestow different functions on the same nucleotide sequence.

Effects of dehydroepiandrosterone and diet protein on liver enzymes and lipogenesis.

ARTICLESEffects of dehydroepiandrosterone and diet protein on liver enzymes and lipogenesisHM Tepperman, SA De la Garza, and J TeppermanHM Tepperman, SA De la Garza, and J TeppermanPublished Online:01 May 1968https://doi.org/10.1152/ajplegacy.1968.214.5.1126MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByHappily at WorkJournal of Biological Chemistry, Vol. 278, No. 6Induction of Thermogenic Enzymes by DHEA and Its MetabolitesAnnals of the New York Academy of Sciences, Vol. 774, No. 1 DehydroepiandDehydroepiandrosterone and Body Fat6 September 2012 | Obesity Research, Vol. 3, No. S4Comparative studies of effects of dehydroepiandrosterone on rat and chicken liverComparative Biochemistry and Physiology Part B: Comparative Biochemistry, Vol. 105, No. 3-4Concerning the mechanism of increased thermogenesis in rats treated with dehydroepiandrosteroneJournal of Bioenergetics and Biomembranes, Vol. 25, No. 3Induction of peroxisomal β-oxidation enzymes by dehydroepiandrosterone and its sulfate in primary cultures of rat hepatocytesBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1137, No. 2Enhancement of Pancreatic Carcinogenesis by DehydroepiandrosteroneGenetic regulation of malic enzyme activity in the mouse.Journal of Biological Chemistry, Vol. 266, No. 32Effects of Dehydroepiandrosterone Treatment in Rats with Diet-Induced ObesityThe Journal of Nutrition, Vol. 120, No. 9Effect of dehydroepiandrosterone treatment on liver metabolism in ratsInternational Journal of Biochemistry, Vol. 22, No. 3Thyroid Hormone-mediated Transcriptional Activation of the Rat Liver Malic Enzyme Gene by DehydroepiandrosteroneJournal of Biological Chemistry, Vol. 264, No. 32Comparison of Dehydroepiandrosterone and Clofibric Acid Treatments in Obese Zucker RatsThe Journal of Nutrition, Vol. 119, No. 3Differential Effects of Adrenalectomy and Starvation-Refeeding on Hepatic Lipogenic Responses to Dehydroepiandrosterone and Glucocorticoid in BHE and Sprague-Dawley RatsThe Journal of Nutrition, Vol. 118, No. 8Lack of an effect of short-term dehydroepiandrosterone treatment on the pentose pathwayNutrition Research, Vol. 8, No. 7Effects of Short-Term Dehydroepiandrosterone Treatment on Serum and Pancreatic Insulin in Zucker RatsThe Journal of Nutrition, Vol. 118, No. 3The in vivo effects of four steroids on glucose‐6‐phosphate dehydrogenase activity of c57L/J mouse erythrocytes15 December 2008 | Journal of Environmental Science and Health . Part A: Environmental Science and Engineering, Vol. 22, No. 6The Effect of Dehydroepiandrosterone on Liver MetabolitesThe Journal of Nutrition, Vol. 116, No. 2Glucose metabolism in isolated adipocytes from lean and obese Zucker rats following treatment with dehydroepiandrosteroneMetabolism, Vol. 34, No. 3Response of sucrose-fed BHE rats to dehydroepiamdrosteroneNutrition Research, Vol. 4, No. 3Chemomorphology of Liver ParenchymaProgress in Histochemistry and Cytochemistry, Vol. 14, No. 3Regulation of the oxidative NADP-enzyme tissue levels inDrosophila melanogaster. II. The biochemical basis of dietary carbohydrate and D-glycerate modulationJournal of Experimental Zoology, Vol. 203, No. 3The effect of phenobarbitone on cytoplasmic NADP-linked dehydrogenase activities in rat liverBiochimica et Biophysica Acta (BBA) - General Subjects, Vol. 539, No. 1Prevention of obesity in Avy/a mice by dehydroepiandrosteroneLipids, Vol. 12, No. 5Regulation of the oxidative NADP-enzyme tissue levels inDrosophila melanogaster. I. Modulation by dietary carbohydrate and lipidJournal of Experimental Zoology, Vol. 195, No. 1Regulation and Physiological Functions of Malic EnzymesEnzymes of carbohydrate and lipid metabolism in the placenta and liver of pregnant ratsBiochimica et Biophysica Acta (BBA) - General Subjects, Vol. 279, No. 3Time Course of the Starve-refeed Response in Rats; the Possible Role of InsulinThe Journal of Nutrition, Vol. 101, No. 11Effect of hypophysectomy on some enzymes involved in lipid metabolism of the domestic chicken (gallus domesticus)Comparative Biochemistry and Physiology Part B: Comparative Biochemistry, Vol. 39, No. 1Differential responses of glucose 6-phosphate dehydrogenase and lipogenesis to fat-free dietsBiochemical Medicine, Vol. 4, No. 5-6Inhibition of lipid synthesis and glucose-6-phosphate dehydrogenase in rat skin by dehydroepiandrosteroneJournal of Lipid Research, Vol. 11, No. 4The Antiobesity Effect of Dehydroepiandrosterone TreatmentRole of Dehydroepiandrosterone in Experimental and Human CarcinogenesisDietary protein and the control of fatty acid synthesis in rat adipose tissueJournal of Lipid Research, Vol. 10, No. 6 More from this issue > Volume 214Issue 5May 1968Pages 1126-1132 Copyright & PermissionsCopyright © 1968 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1968.214.5.1126PubMed4384775History Published online 1 May 1968 Published in print 1 May 1968 Metrics

Effects of D- and L-thyroxine on enzymes in liver and adipose tissue of rats.

ARTICLESEffects of D- and L-thyroxine on enzymes in liver and adipose tissue of ratsJW YoungJW YoungPublished Online:01 Feb 1968https://doi.org/10.1152/ajplegacy.1968.214.2.378MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited Byدراسة بعض تأثيرات إزالة الغدة الزمكية عند عمرين مبكرين على بعض الصفات الإنتاجية والفسيولوجية لطيور دجاج اللحم سلالة Ross31 December 2021 | Al-Mukhtar Journal of Sciences, Vol. 36, No. 4Simultaneous enantioselective separation method for thyroid hormones using liquid chromatography–tandem mass spectrometry and its applicationsJournal of Pharmaceutical and Biomedical Analysis, Vol. 196Effects of perfluorodecanoic acid on hepatic indices of thyroid status in the ratBiochemical Pharmacology, Vol. 36, No. 8Hepatic indices of thyroid status in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxinBiochemical Pharmacology, Vol. 36, No. 2Regulation of hepatic malic enzyme by perfluorodecanoic acidJournal of Biochemical Toxicology, Vol. 1, No. 3Hormonal Regulation of the Expression of the Genes for Malic Enzyme and Fatty Acid SynthaseInhibition of the Effects of Thyroid Hormone On Rat Liver By 5,5'-Diphenylthiohydantoin30 June 2016 | Toxicology and Industrial Health, Vol. 1, No. 1Blood sugar, serum insulin and serum free fatty acid responses to graded glucose pulses in hypothyroid dogsActa Diabetologica Latina, Vol. 19, No. 2Rate of synthesis and degradation of rat liver phosphoenolpyruvate carboxykinase in the different thyroid statesArchives of Biochemistry and Biophysics, Vol. 213, No. 1Nuclear Receptors for Triiodothyronine: A Physiological PerspectiveThe influence of diet on the lipogenic response to thyroxine in rat liverLife Sciences, Vol. 17, No. 12Thyroid function and related hepatic enzymes in the germfree ratMetabolism, Vol. 24, No. 6Die Stoffwechselwirkungen der SchilddrüsenhormoneRegulation and Physiological Functions of Malic EnzymesRegulation of Lipogenesis and the Total Activities of Lipogenic Enzymes in a Primary Culture of Hepatocytes from Prenatal and Early Postnatal ChicksJournal of Biological Chemistry, Vol. 249, No. 5Regulation of fatty-acid synthesis in higher animals23 June 2010Effect of riboflavin deficiency on metabolism of the rat in hyperthyroid and euthyroid stateBiochimica et Biophysica Acta (BBA) - Enzymology, Vol. 268, No. 3Enzyme Activities Related to Fatty-Acid Synthesis in Liver and Adipose Tissue of Rats Treated with TriiodothyronineEuropean Journal of Biochemistry, Vol. 26, No. 4Synthesis and degradation of the lipogenic enzymes of rat liverAdvances in Enzyme Regulation, Vol. 10Interaction of Dietary Fat and Thyroid Function with Hepatic and Renal Gluconeogenesis of RatsThe Journal of Nutrition, Vol. 101, No. 7Fluctuation of Hepatic Enzymes Important in Glucose Metabolism in Relation to Thyroid FunctionEuropean Journal of Biochemistry, Vol. 13, No. 2The Hormonal Control of Hepatic GluconeogenesisThe Role of Thyroid Function in the Metabolism of Perfused Rat Liver with Particular Reference to Gluconeogenesis3 March 2005 | European Journal of Biochemistry, Vol. 10, No. 1Changes of enzyme activities with diet and thyroxine during postnatal development of the ratBiochimica et Biophysica Acta (BBA) - General Subjects, Vol. 170, No. 2 More from this issue > Volume 214Issue 2February 1968Pages 378-383 Copyright & PermissionsCopyright © 1968 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1968.214.2.378PubMed5639563History Published online 1 February 1968 Published in print 1 February 1968 Metrics