Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.37 (malate dehydrogenase)
 4,591 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth of Enterobacter cloacae on K+ citrate under aerated conditions (no detectable oxygen tension in the medium even though it was aerated) was slower (mean generation time, 130 min) than under aerobic conditions (mean generation time, 72 min), but with a faster utilization of citrate, resulting in a molar growth yield of 10.6 g (dry weight) of cells per mol of citrate utilized versus 40 g (dry weight) of cells per mol of citrate utilized for aerobic growth. The rapid utilization of citrate under aerated conditions was apparently due to the induction of citrate lyase and was supported by the finding that cells excreted acetate and a small amount of oxalacetate under aerated conditions, but not under aerobic conditions when the cells were devoid of citrate lyase activity. The activity of oxalacetate decarboxylase in aerated cells was slightly lower than in aerobic cells, indicating that little of the oxalacetate produced by the citrate lyase was metabolized by the decarboxylase. Oxalacetate was probably metabolized by malate dehydrogenase, previously shown to be present in anaerobic and aerobic cells. Thus, about 70% of the citrate was cleaved by the citrate lyase, resulting in little or no production of energy for growth. The remaining citrate was metabolized via the citric acid cycle under aerated conditions, since the cells contained alpha-ketoglutarate dehydrogenase at the same level as in aerobically grown cells. The presence of the other enzymes of the cycle was shown in earlier studies.
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PMID:Induction of citrate lyase in Enterobacter cloacae grown under aerated conditions and its effect on citrate metabolism. 119 31

The content of the Krebs cycle substrates and activity of dehydrogenases corresponding to them were studied in the brain and myocardium tissues of the non-linear male rats adapted to acute hypoxia under conditions of the altered gas medium. The content of malate and succinic acid was studied in the liver and skeletal muscles only. In the brain the total activity of malate dehydrogenase (MDH, EC 1.1.1.37, 1.1.1.39) alpha-ketoglutarate dehydrogenase (KDH, EC 1.2.4.2) pyruvate dehydrogenase (PDH, EC 1.2.4.1) and isocitrate dehydrogenase (ICDH, EC 1.1.1.41-42) is shown to be decreased and kept to be lowered in all the periods of the study. No essential shifts in the activity of these dehydrogenases were found in the myocardium. The activity of succinate dehydrogenase (SDH, EC 1.3.99.1) in both tissues lowers 48 h after the effect of the mentioned factors. Simultaneously the greatest changes in the level of the substrates were observed in the myocardium, in the brain they were less developed. In the liver the content of malate increases without pronounced changes in the amount of succinic acid and in the skeletal muscles the level of malate and succinic acid lowers.
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PMID:[Krebs cycle in tissue of rats subjected to combined effect of hypercapnia, hypoxia and cooling]. 121 51

The level of aspartate aminotransferase in liver mitochondria was found to be approximately 140 microM, or 2-3 orders of magnitude higher than its dissociation constant in complexes with the inner mitochondrial membrane and the high molecular weight enzymes (M(r) = 1.6 x 10(5) to 2.7 x 10(6)) carbamyl-phosphate synthase I, glutamate dehydrogenase, and the alpha-ketoglutarate dehydrogenase complex. The total concentration of aminotransferase-binding sites on these structures in liver mitochondria was more than sufficient to accommodate all of the aminotransferase. Therefore, in liver mitochondria, the aminotransferase could be associated with the inner mitochondrial membrane and/or these high molecular weight enzymes. The aminotransferase in these hetero-enzyme complexes could be supplied with oxalacetate because binding of aminotransferase to the high molecular weight enzymes can enhance binding of malate dehydrogenase, and binding of both malate dehydrogenase and the aminotransferase facilitated binding of fumarase. The level of malate dehydrogenase was found to be so high (140 microM) in liver mitochondria, compared with that of citrate synthase (25 microM) and the pyruvate dehydrogenase complex (0.3 microM), that there would also be a sufficient supply of oxalacetate to citrate synthase-pyruvate dehydrogenase.
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PMID:Glutamate-malate metabolism in liver mitochondria. A model constructed on the basis of mitochondrial levels of enzymes, specificity, dissociation constants, and stoichiometry of hetero-enzyme complexes. 135 Feb 79

The maximal rate (Vmax) of some mitochondrial enzyme activities related to energy transduction (citrate synthase, alpha-ketoglutarate dehydrogenase, malate dehydrogenase, succinate dehydrogenase, NADH-cytochrome c reductase, cytochrome oxidase) and amino acid metabolism (glutamate dehydrogenase, glutamate-pyruvate transaminase and glutamate-oxaloacetate transaminase) are evaluated in non synaptic ("free") and intrasynaptic mitochondria from brain hippocampus. The different mitochondrial populations were isolated from rat subjected to single i.p. treatment with saline solution, almitrine (30 mg/kg) and delta-yohimbine (10 mg/kg). In control rats, the mitochondrial populations exhibit different enzymatic patterns. Acute treatment with almitrine decreases cytochrome oxidase activity in intra-synaptic mitochondria, while acute treatment with delta-yohimbine decreases succinate dehydrogenase activity in both types of free and intra-synaptic mitochondria. NADH-cytochrome c reductase activity is also decreased by acute treatment with almitrine ("free" and "synaptic" mitochondria) and delta-yohimbine (synaptic mitochondria only).
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PMID:Factors involved in drug interference on enzyme activities of three mitochondrial populations from rat hippocampus. 180 34

In several metabolic encephalopathies, hyperammonemia and organic acidemia are consistently found. Ammonia and fatty acids (FAs) are neurotoxic: previous workers have shown that ammonia and FAs can act singly, in combination, or synergistically, in inducing coma in experimental animals. However, the biochemical mechanisms underlying the neurotoxicity of ammonia and FAs have not been fully elucidated. FAs are normally converted to their corresponding CoA derivatives (CoAs) once they enter cells and it is known that these fatty acyl CoAs can alter intermediary metabolism. The present study was initiated to determine the effects of ammonia and fatty acyl CoAs on brain mitochondrial dehydrogenases. At a pathophysiological level (2 mM), ammonia is a potent inhibitor of brain mitochondrial alpha-ketoglutarate dehydrogenase complex (KGDHC). Only at toxicological levels (10-20 mM) does ammonia inhibit brain mitochondrial NAD(+)- and NADP(+)- linked isocitrate dehydrogenase (NAD-ICDH, NADP-ICDH), and NAD(+)-linked malate dehydrogenase (MDH) and liver mitochondrial NAD-ICDH. Butyryl- (BCoA), octanoyl- (OCoA), and palmitoyl (PCoA) CoA were potent inhibitors of brain mitochondrial KGDHC, with IC50 values of 11, 20, and 25 microM, respectively; moreover, the inhibitory effect of fatty acyl CoAs and ammonia were additive. At levels of 250 microM or higher, both OCoA (IC50 = 1.15 mM) and PCoA (IC50 = 470 microM) inhibit brain mitochondrial NADP-ICDH; only at higher levels (0.5-1 mM) does BCoA inhibit this enzyme (by 30-45%). Much less sensitive than KGDHC and NADP-ICDH, brain mitochondrial NAD-ICDH is only inhibited by 1 mM BCoA, OCoA, and PCoA by 22%, 35%, and 44%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neurotoxicity of ammonia and fatty acids: differential inhibition of mitochondrial dehydrogenases by ammonia and fatty acyl coenzyme A derivatives. 194 69

Growth in the presence of glucose, even under highly aerobic conditions, significantly reduced the activities of three tricarboxylic acid cycle enzymes, citrate synthetase, alpha-ketoglutarate dehydrogenase, and malate dehydrogenase, in suicidal but not nonsuicidal Aeromonas strains. Pyruvate dehydrogenase activity, however, was significantly increased. The activities of all of the enzymes, as well as the glucose-mediated increase in acetic acid production, were shown to be regulated by catabolite repression. The regulator protein is the same one which regulates the utilization of several sugars.
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PMID:Glucose-mediated catabolite repression of the tricarboxylic acid cycle as an explanation for increased acetic acid production in suicidal Aeromonas strains. 216 82

Bovine kidney mitochondria were separated into matrix and membrane fractions by treatment with digitonin and Lubrol PX. While malate dehydrogenase was found essentially in the matrix fraction, both the pyruvate and the alpha-oxoglutarate dehydrogenase multienzyme complexes remained bound to the inner membrane fraction and became solubilized only after repeated treatments with detergents. Thus both multienzyme complexes must be associated with the inner membrane rather than located within the matrix space.
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PMID:Localization of the alpha-oxoacid dehydrogenase multienzyme complexes within the mitochondrion. 226 53

The binding of porcine heart mitochondrial malate dehydrogenase and beta-hydroxyacyl-CoA dehydrogenase to bovine heart NADH:ubiquinone oxidoreductase (complex I), but not that of bovine heart alpha-ketoglutarate dehydrogenase complex, is virtually abolished by 0.1 mM NADH. The malate dehydrogenase and beta-hydroxyacyl-CoA enzymes compete in part for the same binding site(s) on complex I as do the malate dehydrogenase and alpha-ketoglutarate dehydrogenase complex enzymes. Associations between mitochondrial malate dehydrogenase and bovine serum albumin were observed. Subtle convection artifacts in short-time centrifugation tests of enzyme association with the Beckman Airfuge are described. Substrate channeling of NADH from both the mitochondrial and cytoplasmic malate dehydrogenase isozymes to complex I and reduction of ubiquinone-1 were shown to occur in vitro by transient enzyme-enzyme complex formation. Excess apoenzyme causes little inhibition of the substrate channeling reaction with both malate dehydrogenase isozymes in spite of tighter equilibrium binding than the holoenzyme to complex I. This substrate channeling could, in principle, provide a dynamic microcompartmentation of mitochondrial NADH.
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PMID:Substrate channeling of NADH and binding of dehydrogenases to complex I. 250 78

Activity levels of pyruvate dehydrogenase, enzymes of citric acid cycle, aspartate and alanine aminotransferases were estimated in mitochondria, synaptosomes and cytosol isolated from brains of normal rats and those injected with acute and subacute doses of ammonium acetate. In mitochondria isolated from animals treated with acute dose of ammonium acetate, there was an elevation in the activities of pyruvate, isocitrate and succinate dehydrogenases while the activities of malate dehydrogenase (malate----oxaloacetate), aspartate and alanine aminotransferases were suppressed. In subacute conditions a similar profile of change was noticed excepting that there was an elevation in the activity of alpha-ketoglutarate dehydrogenase in mitochondria. In the synaptosomes isolated from animals administered with acute dose of ammonium acetate, there was an increase in the activities of pyruvate, isocitrate, alpha-ketoglutarate and succinate dehydrogenases while the changes in the activities of malate dehydrogenase, aspartate and alanine amino transferases were suppressed. In the subacute toxicity similar changes were observed in this fraction except that the activity of malate dehydrogenase (oxaloacetate----malate) was enhanced. In the cytosol, pyruvate dehydrogenase and other enzymes of citric acid cycle except malate dehydrogenase were enhanced in both acute and subacute ammonia toxicity though their activities are lesser than that of mitochondria. In this fraction malate dehydrogenase (oxaloacetate----malate) was enhanced while activities of malate dehydrogenase (malate----oxaloacetate), aspartate and alanine aminotransferases were suppressed in both the conditions. Based on these results it is concluded that the decreased activities of malate dehydrogenase (malate----oxaloacetate) in mitochondria and of aspartate aminotransferase in mitochondria and cytosol may be responsible for the disruption of malate-aspartate shuttle in hyperammonemic state.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activities of pyruvate dehydrogenase, enzymes of citric acid cycle, and aminotransferases in the subcellular fractions of cerebral cortex in normal and hyperammonemic rats. 272 22

We have found previously (Fahien, L.A., Kmiotek, E.H., MacDonald, M. J., Fibich, B., and Mandic, M. (1988) J. Biol. Chem. 263, 10687-10697) that glutamate-malate oxidation can be enhanced by cooperative binding of mitochondrial aspartate aminotransferase and malate dehydrogenase to the alpha-ketoglutarate dehydrogenase complex. The present results demonstrate that glutamate dehydrogenase, which forms binary complexes with these enzymes, adds to this ternary complex and thereby increases binding of the other enzymes. Kinetic evidence for direct transfer of alpha-ketoglutarate and NADH, within these complexes, has been obtained by measuring steady-state rates of E2 when most of the substrate or coenzyme is bound to the aminotransferase or glutamate dehydrogenase (E1). Rates significantly greater than those which can be accounted for by the concentration of free ligand, calculated from the measured values of the E1-ligand dissociation constants, require that the E1-ligand complex serve as a substrate for E2 (Srivastava, D. K., and Bernhard, S. A. (1986) Curr. Tops. Cell Regul. 28, 1-68). By this criterion, NADH is transferred directly from glutamate dehydrogenase to malate dehydrogenase and alpha-ketoglutarate is channeled from the aminotransferase to both glutamate dehydrogenase and the alpha-ketoglutarate dehydrogenase complex. Similar evidence indicates that GTP bound to an allosteric site on glutamate dehydrogenase functions as a substrate for succinic thiokinase. The potential physiological advantages to channeling of activators and inhibitors as well as substrates within multienzyme complexes organized around the alpha-ketoglutarate dehydrogenase complex are discussed.
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PMID:Kinetic advantages of hetero-enzyme complexes with glutamate dehydrogenase and the alpha-ketoglutarate dehydrogenase complex. 274 45


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