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)

Oxidation-reduction midpoint potentials (E(m)) have been measured for the thioredoxin-dependent, reductive activation of sorghum nicotinamide adenine dinucleotide phosphate- (NADP-) dependent malate dehydrogenase (MDH) in the wild-type enzyme and in a number of site-specific mutants. The E(m) value associated with activation of the wild-type enzyme, -330 mV at pH 7.0, can be attributed to the E(m) of the C365/C377 disulfide present in the C-terminal region of the enzyme. The C24/C29 disulfide, located in the N-terminal region of the enzyme and the only other disulfide present in oxidized, wild-type MDH, has a E(m) value of -280 mV at pH 7.0. A third regulatory disulfide, C24/C207, that is absent in the oxidized enzyme but is thought to be formed during the activation process, has an E(m) value at pH 7.0 of -310 mV. E(m) vs pH profiles suggest pK(a) values for the more acidic cysteine involved in the formation of each of these disulfides of 8.5 for C24/C29; 8.1 for C24/C207; and 8.7 for C365/C377. The results of this study show that the N-terminal disulfide formed between C24 and C29 has a more positive E(m) value than the two other disulfides and is thus is likely to be the "preregulatory disulfide" postulated to function in activating the enzyme.
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PMID:Oxidation-reduction properties of the regulatory disulfides of sorghum chloroplast nicotinamide adenine dinucleotide phosphate-malate dehydrogenase. 1072 27

The chloroplastic NADP-malate dehydrogenase is activated by reduction of its N- and C-terminal disulfides by reduced thioredoxin. The activation is inhibited by NADP(+), the oxidized form of the cofactor. Previous studies suggested that the C-terminal disulfide was involved in this process. Recent structural data pointed toward a possible direct interaction between the C terminus of the oxidized enzyme and the cofactor. In the present study, the relationship between the cofactor specificity for catalysis and for inhibition of activation has been investigated by changing the cofactor specificity of the enzyme by substitution of selected residues of the cofactor-binding site. An NAD-specific thiol-regulated MDH was engineered. Its activation was inhibited by NAD(+) but no longer by NADP(+). These results demonstrate that the oxidized cofactor is bound at the same site as the reduced cofactor and support the idea of a direct interaction between the negatively charged C-terminal end of the enzyme and the positively charged nicotinamide ring of the cofactor, in agreement with the structural data. The structural requirements for cofactor specificity are modeled and discussed.
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PMID:Inhibition of the thioredoxin-dependent activation of the NADP-malate dehydrogenase and cofactor specificity. 1080 30

Like many other bacteria, Corynebacterium glutamicum possesses two types of L-malate dehydrogenase, a membrane-associated malate:quinone oxidoreductase (MQO; EC 1.1.99.16) and a cytoplasmic malate dehydrogenase (MDH; EC 1.1.1.37) The regulation of MDH and of the three membrane-associated dehydrogenases MQO, succinate dehydrogenase (SDH), and NADH dehydrogenase was investigated. MQO, MDH, and SDH activities are regulated coordinately in response to the carbon and energy source for growth. Compared to growth on glucose, these activities are increased during growth on lactate, pyruvate, or acetate, substrates which require high citric acid cycle activity to sustain growth. The simultaneous presence of high activities of both malate dehydrogenases is puzzling. MQO is the most important malate dehydrogenase in the physiology of C. glutamicum. A mutant with a site-directed deletion in the mqo gene does not grow on minimal medium. Growth can be partially restored in this mutant by addition of the vitamin nicotinamide. In contrast, a double mutant lacking MQO and MDH does not grow even in the presence of nicotinamide. Apparently, MDH is able to take over the function of MQO in an mqo mutant, but this requires the presence of nicotinamide in the growth medium. It is shown that addition of nicotinamide leads to a higher intracellular pyridine nucleotide concentration, which probably enables MDH to catalyze malate oxidation. Purified MDH from C. glutamicum catalyzes oxaloacetate reduction much more readily than malate oxidation at physiological pH. In a reconstituted system with isolated membranes and purified MDH, MQO and MDH catalyze the cyclic conversion of malate and oxaloacetate, leading to a net oxidation of NADH. Evidence is presented that this cyclic reaction also takes place in vivo. As yet, no phenotype of an mdh deletion alone was observed, which leaves a physiological function for MDH in C. glutamicum obscure.
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PMID:Functions of the membrane-associated and cytoplasmic malate dehydrogenases in the citric acid cycle of Corynebacterium glutamicum. 1109 46

In the polymorphic Teladorsagia circumcincta (morphs circumcincta and trifurcata), a sheep and goat line (SGL) and a goat line (GL) have been previously described on the basis of the malate dehydrogenase allozyme polymorphism (MDH-2) and of the morphology of the dorsal ray. The GL were never found alone in 1 host, so the status of species was not given to these 2 lines. To investigate further whether there are other genetic markers that will delineate them, we collected T. circumcincta worms from goat and sheep at 8 farms in Touraine (west-central France). The worms were identified individually as being SGL or GL on the basis of MDH-2 polymorphism. This distinctiveness was corroborated by sequences of the beta-tubulin isotype I gene, the second internal transcribed spacer (ITS2) of their rDNA, and the nicotinamide dehydrogenase (ND4) gene of their mDNA. The extent of the divergence in the 3 additional genetic markers was such that SGL and GL may be considered as 2 species. A third putative species was found in the SGL line based exclusively on the ND4 gene. These findings suggest that T. circumcincta is a species complex and that further investigation is required on a wider geographic scale.
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PMID:New molecular evidence that Teladorsagia circumcincta (Nematoda: Trichostrongylidea) is a species complex. 1205 53

The extremely halophilic bacterium Salinibacter ruber was previously shown to have a high intracellular potassium content, comparable to that of halophilic Archaea of the family Halobacteriaceae. The amino acid composition of its bulk protein showed a high content of acidic amino acids, a low abundance of basic amino acids, a low content of hydrophobic amino acids, and a high abundance of serine. We tested the level of four cytoplasmic enzymatic activities at different KCl and NaCl concentrations. Nicotinamide adenine dinucleotide (NAD)-dependent isocitrate dehydrogenase functioned optimally at 0.5-2 M KCl, with rates of 60% of the optimum value at 3.3 M. NaCl provided less activation: 70% of the optimum rates in KCl were found at 0.2-1.2 M NaCl, and above 3 M NaCl, activity was low. We also detected nicotinamide adenine dinucleotide phosphate (NADP)-dependent isocitrate activity, which remained approximately constant between 0-3.2 M NaCl and increased with increasing KCl concentration. NAD-dependent malate dehydrogenase functioned best in the absence of salt, but rates as high as 25% of the optimal values were measured in 3-3.5 M KCl or NaCl. NAD-dependent glutamate dehydrogenase, assayed by the reductive amination of 2-oxoglutarate, showed low activity in the absence of salt. NaCl was stimulatory with optimum activity at 3-3.5 M. However, no activity was found above 2.5 M KCl. Although the four activities examined all function at high salt concentrations, the behavior of individual enzymes toward salt varied considerably. The results presented show that Salinibacter enzymes are adapted to function in the presence of high salt concentrations.
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PMID:Amino acid composition of bulk protein and salt relationships of selected enzymes of Salinibacter ruber, an extremely halophilic bacterium. 1207 57

The cytoplasmic coenzyme NAD(+)-dependent alcohol (methanol) dehydrogenase (MDH) employed by Bacillus methanolicus during growth on C(1)-C(4) primary alcohols is a decameric protein with 1 Zn(2+)-ion and 1-2 Mg(2+)-ions plus a tightly bound NAD(H) cofactor per subunit (a nicotinoprotein). Mg(2+)-ions are essential for binding of NAD(H) cofactor in MDH protein expressed in Escherichia coli. The low coenzyme NAD(+)-dependent activity of MDH with C(1)-C(4) primary alcohols is strongly stimulated by a second B. methanolicus protein (ACT), provided that MDH contains NAD(H) cofactor and Mg(2+)-ions are present in the assay mixture. Characterization of the act gene revealed the presence of the highly conserved amino acid sequence motif typical of Nudix hydrolase proteins in the deduced ACT amino acid sequence. The act gene was successfully expressed in E. coli allowing purification and characterization of active ACT protein. MDH activation by ACT involved hydrolytic removal of the nicotinamide mononucleotide NMN(H) moiety of the NAD(H) cofactor of MDH, changing its Ping-Pong type of reaction mechanism into a ternary complex reaction mechanism. Increased cellular NADH/NAD(+) ratios may reduce the ACT-mediated activation of MDH, thus preventing accumulation of toxic aldehydes. This represents a novel mechanism for alcohol dehydrogenase activity regulation.
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PMID:Molecular, biochemical, and functional characterization of a Nudix hydrolase protein that stimulates the activity of a nicotinoprotein alcohol dehydrogenase. 1208 58

The effects of sex, genotype, and adipose depot on lipogenic enzyme activity have been investigated in Holstein and Pirenaican bulls and heifers, taking into account differences in adipocyte size. Fifteen Pirenaican bulls and 15 heifers and 15 Holstein bulls and 13 heifers were fattened until slaughter (12 to 13 mo old and 450 to 500 kg of body weight). During the fattening period, animals had ad libitum access to commercial concentrates and straw. The 10th rib was dissected to determine the fat content. Adipocyte size and activities of the following lipogenic enzymes were determined: glycerol 3-phosphate dehydrogenase, fatty acid synthase, nicotinamide adenine dinucleotide phosphate (NADP)-malate dehydrogenase, glucose 6-phosphate dehydrogenase, and NADP-isocitrate dehydrogenase, in the omental, perirenal, subcutaneous, and intermuscular adipose depots, respectively. Because adipocyte mean cell volume varied with sex, breed, and depot, regression analyses of log(e) activity per cell and log(e) cell volume were used to compare activities per unit volume. Sex, breed and depot had no effect (P > 0.05) on the gradients of regressions, which did not differ significantly from 1. Thus, activity per unit volume did not vary with cell size. Consequently, sex, breed, and depot effects on the regression analyses were equivalent to effects on activity per unit volume. Females had greater amounts of fat in the 10th rib (P < 0.001), larger adipocytes (P < 0.001) and, in general, greater (P < 0.05) lipogenic activity per cell, even when adjusted for cell size, than males. These findings suggest that differences in adiposity between sexes are mainly due to females having a greater capacity for lipid synthesis, and hence, hypertrophy, than males. When adjusted for differences in carcass weight, Holsteins had larger adipocytes than Pirenaicans. The abdominal depots, omental and perirenal, had a greater adipocyte size (P < 0.001) and, in general, greater lipogenic enzyme activities per cell (P < 0.05) than the subcutaneous and intermuscular carcass depots. However, when activity per cell was adjusted for cell size, subcutaneous depots had greater fatty acid synthae, glucose 6-phosphate dehydrogenase, and NADP-malate dehydrogenase activities than omental and perirenal, indicating that other factors such as nutrient supply may restrict hypertrophy of carcass adipocytes.
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PMID:Lipogenic enzyme activities in different adipose depots of Pirenaican and Holstein bulls and heifers taking into account adipocyte size. 1264 87

The malic dehydrogenase activity was determined by the modified method of Ochoa (1955) using tissue homogenates of various parasitic helminths. Worm parasites were mostly collected from local abattoir, and removed from the organ or tissues of the naturally infected animal hosts, and some materials were also obtained from the human hosts. The helminths used in this experiment include 3 kinds of nematodes, 5 kinds of trematodes, and 8 kinds of cestodes. They were throughly washed and homogenized in glass tissue grinder in ice chilled water bath, and then centrifuged. The supernatants were designated as enzyme preparations. The hydrogen concentrations of buffer solution were pH 1.4, 2.7, 3.5, 4.2, 5.2, 7.4, 8.2, 9.3, 10.2, 11.6, and enzymatic reaction of this experiment was performed at incubation temperature of 20, 30, 40, and 50 degrees C. The extinction of Nicotinamide Adenosine Dinucleotide (NAD) was measured by spectrophotometry at the wave length of 340 millimicron. The results of the experiment were as follows: 1. The malic dehydrogenase activity occurred over all kinds of parasitic helminths used in this study. And the activity on sparganum turned out to be highest. 2. All helminths displayed their maximum activity in the range of alkaline pH. 3. A comparison of the effects of temperature and substrate concentration on the enzyme activity was made among these helminths. However, no definite relationship among them has been detected. 4. The significance of the existence of this enzyme in the helminths was briefly discussed.
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PMID:[Studies On Malic Dehydrogenase Activity In Parasitic Helminths] 1291 53

Dowler, William M. (University of Illinois, Urbana), Paul D. Shaw, and David Gottlieb. Terminal oxidation in cell-free extracts of fungi. J. Bacteriol. 86:9-17. 1963.-The terminal respiration in cell-free extracts of ten representative fungi is mediated by an electron transport system similar to that observed in animal tissue. Reduced nicotinamide adenine dinucleotide (NADH) and succinic cytochrome c reductases and NADH oxidase activity are contained in the extracts. An antimycin-sensitive site and cytochrome oxidase are present. Dehydrogenases including glucose-6-phosphate, triose phosphate, isocitric, glutamic, succinic, and malic dehydrogenase were found, but pyruvic and alpha-ketoglutaric dehydrogenases were absent. The soluble nature of the dehydrogenases indicates probable disruption of the mitochondria, since normally these enzymes are found within the mitochondria. Particles containing most of the terminal respiratory activity could be sedimented by centrifugation at 40,000 x g for 30 min. Oxygen was utilized by cell-free extracts with NADH, succinate, and isocitrate as substrates, but not with glucose.
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PMID:TERMINAL OXIDATION IN CELL-FREE EXTRACTS OF FUNGII. 1405 29

Experiments with analogs of the coenzyme nicotinamide adenine dinucleotide demonstrate that the molecular forms of malate dehydrogenase in Euglena vary with the nutritional environment. Electrophoretic separations on starch gel show that Euglena grown on autotrophic medium has a malate dehydrogenase which is lacking in Euglena grown on heterotrophic medium.
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PMID:MOLECULAR HETEROGENEITY OF ENZYMES: MALATE DEHYDROGENASE OF EUGLENA. 1405 55


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