Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:1.1.1.37 (malate dehydrogenase)
4,591 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The apoenzyme and holoenzyme structures of liver alcohol dehydrogenase have been determined by X-ray methods to obtain details about coenzyme binding, substrate specificity and the catalytic mechanism. Coenzyme binding induces a conformational change of the protein which partly shields the active site from the solution. The reduced coenzyme binds in an open conformation similar to that of NAD bound to malate dehydrogenase. A hydrogen bond between Thr-178 and the carboxamide group of the coenzyme is essential for proper positioning of the nicotinamide in the active site. Coenzyme analogues in which the carboxamide group is absent or substituted with iodine bind in a different conformation and do not induce the structural change of the protein. Binding of substrate molecules has been studied in crystals obtained from an equilibrium mixture of enzyme, coenzyme and p-bromobenzyl alcohol. The oxygen atom of this substrate as well as that of the inhibitor molecules trifluoroethanol and dimethyl sulphoxide bind directly to the catalytic zinc atom. The substrate-binding region is a deep hydrophobic pocket at the bottom of which the zinc atom mediates electrophilic catalysis of alcohol oxidation.
...
PMID:Coenzyme-induced conformational changes and substrate binding in liver alcohol dehydrogenase. 21 94

Nicotinamide adenine dinucleotide-linked malate dehydrogenase has been purified from Pseudomonas testosteroni (ATCC 11996). The purification represents over 450-fold increase in specific activity. The amino acid composition of the enzyme was determined and found to be quite different from the composition of the malate dehydrogenases from animal sources as well as from Escherichia coli. Despite this difference, however, the data show that the enzymatic properties of the purified enzyme are remarkably similar to those of other malate dehydrogenases that have been previously studied. The Pseudomonas enzyme has a molecular weight of 74,000 and consists of two subunits of identical size. In addition to L-malate, the enzyme slowly oxidizes other four-carbon dicarboylates having an alpha-hydroxyl group of S configuration such as meso- and (-) tartrate. Rate-determining steps, which differ from that of the reaction involving L-malate, are discussed for the reaction involving these alternative substrates. Oxidation of hydroxymalonate, a process previously undetected with other malate dehydrogenases, is demonstrated fluorometrically. Hydroxymalonate and D-malate strongly enhance the fluorescence of the reduced nicotinamide adenine dinucleotide bound to the enzyme. The enzyme is A-stereospecific with respect to the coenzyme. Malate dehydrogenase is present in a single form in the Pseudomonas. The susceptibility of the enzyme to activation or inhibition by its substrates-particularly the favoring of the oxidation of malate at elevated concentrations-strongly resembles the properties of the mitochondrial enzymes. The present study reveals that whereas profound variations in chemical composition have occurred between the prokaryotic and eukaryotic enzymes, the physical and catalytic properties of malate dehydrogenase, unlike lactate dehydrogenase, are well conserved during the evolutionary process.
...
PMID:Purification and properties of malate dehydrogenase from Pseudomonas testosteroni. 23 57

In order to obtain a quantitative estimate of the capacity of the pancreatic islets for provision of cytoplasmic acetyl-coenzyme A and for the turnover of nicotinamide adenine dinucleotide phosphate and its reduced form (NADP+/NADPH), the following enzymes were assayed in islets taken from New Zealand Obese mice: adenosine triphosphate citrate lyase (EC 4.1.3.8), malate dehydrogenase (decarboxylating) (NADP+) (EC 1.1.1.40), glutathione reductase (EC 1.6.4.2) and isocitrate dehydrogenase (NADP+) (EC 1.1.1.42). In addition, the activity of isocitrate dehydrogenase (NAD+) (EC 1.1.1.41) was determined. For comparative purposes the activities in exocrine pancreas, liver, heart muscle, kidney cortex and skeletal muscle were also determined. Specimens of pancreatic islets and the other tissues were microdissected from freeze-dried sections. In comparison with the other tissues, adenosine triphosphate citrate lyase was particularly active in the islets. The NADP+/NAPH-converting enzymes had activities, which suggested a rapid turnover of the islet NADP+/NADPH pool.
...
PMID:Nicotinamide adenine dinucleotide phosphate-converting enzymes and adenosine triphosphate citrate lyase in some tissues and organs of New Zealand obese mice with special reference to the enzyme pattern of the pancreatic islets. 24 Aug 82

Ultrastructural morphometric and biochemical studies were conducted on hepatic mitochondria from control rats and rats treated in vivo with arsenate to examine changes in interrelationships between mitochondrial structure and biochemical functions. Morphometric analysis disclosed an over-all 1.2-fold increase in the relative mitochondrial volume density and 1.4-fold increase in the surface density of the inner mitochondrial membrane of arsenate-exposed rats. These structural changes were associated with a 1.5-fold increase in 14C-leucine incorporation into all mitochondrial proteins, which was primarily associated with the acid-insoluble membranous fraction. Mitochondria from arsenate-treated rats showed a marked disruption of normal conformational behavior with depression of nicotinamide adenine dinucleotide (NAD)-linked substrate oxidation and a resulting in vivo increase in the mitochondrial [NAD] to [NADH] ratio. Observed changes in mitochondrial membranes from arsenate exposure also resulted in 1.5- to 2-fold increases in the specific activities of the membrane marker enzymes monoamine oxidase, cytochrome oxidase, and Mg2+-ATPase. Activity of malate dehydrogenase, which is localized in the mitochondrial matrix, was unchanged. The results of this study demonstrate a positive quantitative in vivo correlation between mitochondrial structure and function and indicate a marked dependency upon membrane integrity for normal maintenance of the specific biologic activities performed by this organelle in vivo.
...
PMID:Studies of hepatic mitochondrial structure and function: morphometric and biochemical evaluation of in vivo perturbation by arsenate. 49 44

The pathway of acetate assimilation in Methanosarcina barkeri was determined from analysis of the position of label in alanine, aspartate, and glutamate formed in cells grown in the presence of [14C]acetate and by measurement of enzyme activities in cell extracts. The specific radioactivity of glutamate from cells grown on [1-14C]- or [2-14C]acetate was approximately twice that of aspartate. The methyl and carboxyl carbons of acetate were incorporated into aspartate and glutamate to similar extents. Degradation studies revealed that acetate was not significantly incorporated into the C1 of alanine, C1 or C4 of aspartate, or C1 of glutamate. The C5 of glutamate, however, was partially derived from the carboxyl carbon of acetate. Cell extracts were found to contain the following enzyme activities, in nanomoles per minute per milligram of protein at 37 degrees C: F420-linked pyruvate synthase, 170; citrate synthase, 0.7; aconitase, 55; oxidized nicotinamide adenine dinucleotide phosphate-linked isocitrate dehydrogenase, 75; and oxidized nicotinamide adenine dinucleotide-linked malate dehydrogenase, 76. The results indicate that M. barkeri assimilates acetate into alanine and aspartate via pyruvate and oxaloacetate and into glutamate via citrate, isocitrate, and alpha-ketoglutarate. The data reveal differences in the metabolism of M. barkeri and Methanobacterium thermoautotrophicum and similarities in the assimilation of acetate between M. barkeri and other anaerobic bacteria, such as Clostridium kluyveri.
...
PMID:Acetate assimilation pathway of Methanosarcina barkeri. 76 16

A technique for studying the catalytic activity of enzymes spread as a film at an air-water interface, by exchanging the subphase under the film to remove unspread enzyme molecules, was developed, and its effectiveness was studied using surface-spread mitochondrial malate dehydrogenase. Mitochondrial malate dehydrogenase formed stable films which gave reproducible pi-A curves. The enzyme activity was measured by the oxidation rate of reduced nicotinamide adenine dinucleotide (NADH) in the presence of the substrate oxalacetic acid. Oxalacetic acid and NADH were injected into the subphase. The catalytic activity of the enzyme was dependent on the surface pressure of the film. The maximum catalytic activity was observed at a surface pressure of 4.4 dynes/cm. The activity was higher at intermediate surface pressures than at very low or very high surface pressures. A high bulk catalytic activity was observed in the unstable region, i.e., at a high degree of compression, of the film. The catalytic activity of the surface-spread enzyme was only a fraction of an equivalent amount of enzyme in solution.
...
PMID:Enzymatic activity of pig heart mitochondrial malate dehydrogenase monomolecular films by surface exchange technique. 87 77

Cell-free extracts of Methanobacterium thermoautotrophicum were found to contain high activities of the following oxidoreductases (at 60 degrees C): pyruvate dehydrogenase (coenzyme A acetylating), 275 nmol/min per mg of protein; alpha-ketoglutarate dehydrogenase (coenzyme A acylating), 100 nmol/min per mg; fumarate reductase, 360 nmol/min per mg; malate dehydrogenase, 240 nmol/min per mg; and glyceraldehyde-3-phosphate dehydrogenase, 100 nmol/min per mg. The kinetic properties (apparent V(max) and K(M) values), pH optimum, temperature dependence of the rate, and specificity for electron acceptors/donors of the different oxidoreductases were examined. Pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase were shown to be two separate enzymes specific for factor 420 rather than for nicotinamide adenine dinucleotide (NAD), NADP, or ferredoxin as the electron acceptor. Both activities catalyzed the reduction of methyl viologen with the respective alpha-ketoacid and a coenzyme A-dependent exchange between the carboxyl group of the alpha-ketoacid and CO(2). The data indicate that the two enzymes are similar to pyruvate synthase and alpha-ketoglutarate synthase, respectively. Fumarate reductase was found in the soluble cell fraction. This enzyme activity coupled with reduced benzyl viologen as the electron donor, but reduced factor 420, NADH, or NADPH was not effective. The cells did not contain menaquinone, thus excluding this compound as the physiological electron donor for fumarate reduction. NAD was the preferred coenzyme for malate dehydrogenase, whereas NADP was preferred for glyceraldehyde-3-phosphate dehydrogenase. The organism also possessed a factor 420-dependent hydrogenase and a factor 420-linked NADP reductase. The involvement of the described oxidoreductases in cell carbon synthesis is discussed.
...
PMID:Oxidoreductases involved in cell carbon synthesis of Methanobacterium thermoautotrophicum. 91 79

Temperature studies have indicated that from 0 to 37 degrees, the time-dependent inactivation of mitochondrial malate dehydrogenase from porcine heart by pyridoxal 5-phosphate (pyridoxal-5-P) is biphasic. The initial phase of the inactivation is reversible but can be made irreversible by reduction with sodium borohydride. The reduced pryidoxal-5-P-enzyme adduct exhibits a new absorbance maximum at 325 nm and a fluorescence emission at 392 nm when excited at 325. The irreversible second phase of the inactivation is accompanied by the appearance of a new 325-nm absorbance maximum, in the absence of reduction, and a fluorescence emission centered about 390 to 400 nm when excited at 325. The evidence presented suggests the formation of a Schiff base between pyridoxal-5-P and a nucleophilic residue, most likely lysine, of malate dehydrogenase during the first phase of inactivation. An X-azolidine-like structure, a further derivative of the Schiff base, possessing spectral properties consistent with the reported data, may be formed during the second phase; this presumably involves a second nucleophilic residue of the enzyme, implicating the action of pyridoxal-5-P as a bifunctional reagent in this instance. The presence of the coenzyme, NADH, protects the enzyme from inactivation, suggesting that pyridoxal-5-P interacts at or near the malate dehydrogenase active center. Simultaneous binding studies using pyridoxal-5-P with known malate dehydrogenase competitive inhibitors AMP, ADP, and nicotinamide indicate that the pyridoxal-5-P modification occurs in the general area of the ADP portion of the coenzyme binging site. Furthermore, the presence of nicotinamide enhances pyridoxal-5-P binding to and inactivation of malate dehydrogenase.
...
PMID:Biphasic inactivation of procine heart mitochondrial malate dehydrogenase by pyridoxal 5'-phosphate. 111 83

The facultative anaerobes Bacillus polymyxa Hino G, B. polymyxa Hino J, and B.macerans were observed to have imcomplete tricarboxylic acid cycles. They were devoid of malate dehydrogenase and all had very low levels of alpha-ketoglutarate dehydrogenase. B. polymyxa Hino J was devoid of alpha-ketoglutarate dehydrogenase when grown aerobically and anerobically. Citrate synthase from B. polymyxa was inhibited by adenosine triphosphate but not reduced nicotinamide adenine dinucleotide and resembled enzymes from other gram-positive bacteria in this respect. Like the citrate synthases from gram-negative, facultative anaerobes and chemolithotrophs, the enzyme from B. polymyxa was inhibited by alpha-ketoglutarate. Inhibition by adenosine triphosphate was shown to be competitive with acetyl-coenzyme A and alpha-ketoglutarate inhibition was competitive with oxaloacetate.
...
PMID:Regulation of the tricarboxylic acid cycle in gram-positive, facultatively anaerobic bacilli. 112 17

The inactivation of cytoplasmic malate dehydrogenase (L-malate: NAD+ oxidoreductase, EC 1.1.1.37) from porcine heart and the specific modification of arginyl residues have been found to occur when the enzyme is inhibited with the reagent butanedione in sodium borate buffer. The inactivation of the enzyme was found to follow pseudo-first order kinetics. This loss of enzymatic activity was concomitant with the modification of 4 arginyl residues per molecule of enzyme. All 4 residues could be made inaccessible to modification when a malate dehydrogenase-NADH-hydroxymalonate ternary complex was formed. Only 2 of the residues were protected by NADH alone and appear to be essential. Studies of the butanedione inactivation in sodium phosphate buffer and of reactivation of enzymatic activity, upon the removal of excess butanedione and borate, support the role of borate ion stabilization in the inactivation mechanism previously reported by Riordan (Riordan, J.F. (1970) Fed. Proc. 29, Abstr. 462; Riordan, J.F. (1973) Biochemistry 12, 3915-3923). Protection from inactivation was also provided by the competitive inhibitor AMP, while nicotinamide exhibited no effect. Such results suggest that the AMP moiety of the NADH molecule is of major importance in the ability of NADH to protect the enzyme. When fluorescence titrations were used to monitor the ability of cytoplasmic malate dehydrogenase to form a binary complex with NADH and to form a ternary complex with NADH and hydroxymalonate, only the formation of ternary complex seemed to be effected by arginine modification.
...
PMID:Identification of essential arginyl residues in cytoplasmic malate dehydrogenase with butanedione. 115 61


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---