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

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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)

The possibility that some of the enzymes of the citric acid cycle may be loosely associated into a multienzyme cluster has been investigated using extracts prepared by gentle disruption of cells. Gel filtration and sucrose density gradient centrifugation have shown that five sequential enzymes of the cycle specifically associate into a cluster: fumarase, malate dehydrogenase, citrate synthase, aconitase and isocitrate dehydrogenase. Ultrasonication destroys the abilities of the enzymes to associate. The cluster could catalyse the sequence of reactions leading from fumarate to oxoglutarate and has been found in extracts of several bacterial species as well as rat liver mitochondria.
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PMID:Organization of citric acid cycle enzymes into a multienzyme cluster. 308 26

On the basis of enzyme activities detected in extracts of Selenomonas ruminantium HD4 grown in glucose-limited continuous culture, at a slow (0.11 h-1) and a fast (0.52 h-1) dilution rate, a pathway of glucose catabolism to lactate, acetate, succinate, and propionate was constructed. Glucose was catabolized to phosphoenol pyruvate (PEP) via the Emden-Meyerhoff-Parnas pathway. PEP was converted to either pyruvate (via pyruvate kinase) or oxalacetate (via PEP carboxykinase). Pyruvate was reduced to L-lactate via a NAD-dependent lactate dehydrogenase or oxidatively decarboxylated to acetyl coenzyme A (acetyl-CoA) and CO2 by pyruvate:ferredoxin oxidoreductase. Acetyl-CoA was apparently converted in a single enzymatic step to acetate and CoA, with concomitant formation of 1 molecule of ATP; since acetyl-phosphate was not an intermediate, the enzyme catalyzing this reaction was identified as acetate thiokinase. Oxalacetate was converted to succinate via the activities of malate dehydrogenase, fumarase and a membrane-bound fumarate reductase. Succinate was then excreted or decarboxylated to propionate via a membrane-bound methylmalonyl-CoA decarboxylase. Pyruvate kinase was inhibited by Pi and activated by fructose 1,6-bisphosphate. PEP carboxykinase activity was found to be 0.054 mumol min-1 mg of protein-1 at a dilution rate of 0.11 h-1 but could not be detected in extracts of cells grown at a dilution rate of 0.52 h-1. Several potential sites for energy conservation exist in S. ruminantium HD4, including pyruvate kinase, acetate thiokinase, PEP carboxykinase, fumarate reductase, and methylmalonyl-CoA decarboxylase. Possession of these five sites for energy conservation may explain the high yields reported here (56 to 78 mg of cells [dry weight] mol of glucose-1) for S. ruminantium HD4 grown in glucose-limited continuous culture.
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PMID:Pathway and sites for energy conservation in the metabolism of glucose by Selenomonas ruminantium. 314 85

The malate dehydrogenase gene of Escherichia coli, which is susceptible to catabolite and anaerobic repression, has been cloned using plasmic pLC32-38 of Clarke and Carbon (1976). The nucleotide sequence was determined of a 2.47 kbp fragment, containing the mdh structural gene. All information necessary for expression of the mdh structural gene was mapped within a 1.3 kbp SphI-BstEII fragment. Compared with the untransformed wild type, transformations with pUC19 vector, containing this fragment, gave up to 40-fold more malate dehydrogenase activity in both E. coli wild type and mdh mutant recipients. Catabolite repression was not affected in the transformants. A possible CRP binding site in the promotor region of the mdh gene provides evidence for a co-regulation with fumA gene, the structural gene of fumarase, which is also subject to catabolite repression. The structures for transcription initiation and termination were similar to those previously described for E. coli. Amino acid sequence homologies between pro- and eucaryotic malate dehydrogenases are discussed.
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PMID:Cloning and sequence of the mdh structural gene of Escherichia coli coding for malate dehydrogenase. 332 23

A general analysis of the regulation of the citric acid cycle is hampered by the intimate interplay believed to exist between the various surrounding pathways. Two main regulatory mechanisms are thought to determine the flux through the cycle: (1) regulation of individual cycle enzymes, and (2) reversible complex formation between various enzymes of the cycle and related pathways. The latter mechanism allows a cell to maintain a high flux of substrates with a moderate number of intermediates, and offers a means of metabolite channeling. We were able to demonstrate specific interactions between several vertebrate cycle enzymes in conditions of reduced water concentration, i.e. by using immobilized enzyme systems. From affinity chromatographic experiments, we have shown that the enzymes of the citric acid cycle and the aspartate-malate shuttle are organized as one huge multi-enzyme complex, and a stoichiometric arrangement of fumarase/malate dehydrogenase/citrate synthase/aspartate aminotransferase has been postulated. Affinity electrophoresis was used as a new experimental device by which the enzyme-enzyme interactions could be directly visualized.
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PMID:Enzyme-enzyme interactions as modulators of the metabolic flux through the citric acid cycle. 333 92

The specific interaction of yeast citrate synthase with yeast mitochondrial inner membranes was characterized with respect to saturability of binding, pH optimum, effect of ionic strength, temperature response, and inhibition by oxalacetate. The binding ability of the inner membranes is inhibited by proteolysis and heat treatment, which implies that the membrane component(s) responsible for binding is a protein. A protein fraction from inner membranes when added to liposomes will bind citrate synthase. In addition, the binding of yeast fumarase, mitochondrial malate dehydrogenase, and cytosolic malate dehydrogenase to yeast inner membranes was examined. For these studies the yeast mitochondrial matrix enzymes, citrate synthase (from two types of yeast), malate dehydrogenase, and fumarase, as well as cytosolic malate dehydrogenase, were purified using rapid new techniques.
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PMID:The interaction of yeast citrate synthase with yeast mitochondrial inner membranes. 353 36

The role of the isocitrate dehydrogenases and other Krebs cycle enzymes in bovine mammary metabolism was studied by investigation of their distribution between cytosol and mitochondria. Citrate synthase was used as a marker for mitochondrial disruption, and distributions were normalized to this enzyme. Aconitase, fumarase, and NAD+:malate dehydrogenase were distributed between the mitochondria and the cytosol; evidence for the possible involvement of an aspartate:malate shuttle was also found. The NADP+:isocitrate dehydrogenase is predominantly cytosolic with a small but significant amount of mitochondrial component. Using the dye dichlorophenol-indophenol, a low level of NAD+:isocitrate dehydrogenase activity was observed in bovine mammary tissues. This assay also allows for detection of the enzyme in fresh mitochondria from a variety of other bovine tissues (heart, liver, kidney, and brain). Activities of the isocitrate dehydrogenases were also examined as a function of gestation and lactation. The NAD+:isocitrate dehydrogenase is apparently depressed during gestation with the NADP+ form of the enzyme (cytosolic) elevated postpartum. These results indicate that a substantial portion of Krebs cycle activity may become extramitochondrial in bovine mammary gland at the onset of lactation.
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PMID:Role of the isocitrate dehydrogenases and other Krebs cycle enzymes in lactating bovine mammary gland. 358 14

3-Hydroxyacyl coenzyme A (CoA) dehydrogenase-binding protein was solubilized from inner mitochondrial membrane by using taurodeoxycholate at high ionic strength. The binding protein was isolated from the suspension using 3-hydroxyacyl-CoA dehydrogenase affinity chromatography. The protein eluted from the affinity column had a molecular weight of approximately 150,000, as determined by gel filtration. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the protein is a dimer consisting of 69,000 and 71,000 molecular weight subunits. The enzyme binding capacity of this protein was tested with a polyethylene glycol precipitation method: 0.5 mg of enzyme could be precipitated together with 1 mg of binding protein, showing that 1 mol of binding protein binds 1 mol of enzyme. This protein had no affinity toward malic dehydrogenase, citrate synthase, and fumarase. The approximately 2-fold increase in the 3-hydroxyacyl-CoA dehydrogenase activity when it was measured in the presence of the binding protein is additional evidence of enzyme-binding protein interaction. When incorporated into liposomes, the binding protein retained its ability to bind 3-hydroxyacyl-CoA dehydrogenase, but did not bind malic dehydrogenase, citrate synthase, and fumarase. These results suggest that the protein isolated by us has a specific function in anchoring a beta-oxidation enzyme to the matrix surface of the mitochondrial membrane.
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PMID:Isolation and characterization of 3-hydroxyacyl coenzyme A dehydrogenase-binding protein from pig heart inner mitochondrial membrane. 377 31

Glutamine is utilized at a high rate (fourfold higher than that of glucose) by isolated incubated lymphocytes and produces glutamate, aspartate, lactate and ammonia. The pathway for glutamine metabolism includes the reactions catalysed by glutaminase, aspartate aminotransferase, oxoglutarate dehydrogenase, succinate dehydrogenase, fumarase, malate dehydrogenase and phosphoenolpyruvate carboxykinase. In fact little if any of the carbon of the glutamine that is used is converted to acetyl-CoA for complete oxidation. For this reason, the oxidation of glutamine is only partial and, in an analogous manner to the terminology used to describe the partial oxidation of glucose to lactate as glycolysis, the term glutaminolysis is used to describe the process of partial glutamine oxidation. The role of glutaminolysis in lymphocytes and perhaps other rapidly dividing cells is to provide both nitrogen and carbon for precursors for synthesis of macromolecules (e.g. purines and pyrimidines for DNA and RNA) and also energy. However, the rate of glutamine utilization by lymphocytes is markedly in excess of the precursor requirements (which are at most 4%) and if glutamine was vitally important in energy production it would be expected that more would be converted to acetyl-CoA for complete oxidation via the Krebs cycle. Indeed most of the energy for lymphocytes may be obtained by the complete oxidation of fatty acids and ketone bodies. Consequently the role of the high rate of glutaminolysis in lymphocytes and other rapidly dividing cells may be identical to that of glycolysis: the high rates provide ideal conditions for the precise and sensitive control of the rate of use of the intermediates of these pathways for biosynthesis when required. High rates of glycolysis and glutaminolysis can be seen as part of a mechanism of control to permit synthesis of macromolecules when required without any need for extracellular signals to make more glucose or glutamine available for these cells. In order to maintain a high rate of glutaminolysis despite fluctuation in the plasma level of glutamine, the flux through the glutaminolytic pathway can be controlled and the key processes in the lymphocyte that may play a role in this process include glutamine transport across the cell and mitochondrial membranes, glutaminase and oxoglutarate dehydrogenase. Changes in the intracellular concentration of Ca2+ may play a role in control of one or more of these reactions.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Glutamine metabolism in lymphocytes: its biochemical, physiological and clinical importance. 390 97

Oxaloacetate keto-enol tautomerase, partially purified from porcine kidney, catalyzes the conversion of enol- to keto-oxaloacetate by a mechanism in which solvent protons end up equally distributed between the two prochiral positions at C3 of keto-oxaloacetate. This conclusion is based upon the observation that when enzyme catalyzed ketonization is conducted in 3H2O in the presence of excess malate dehydrogenase and NADH, only 50% of the 3H in the isolated (2S)-[3-3H]malate is labilized to solvent upon treatment with fumarase. From a stereochemical perspective, this enzyme is unlike phenylpyruvate keto-enol tautomerase that is known to catalyze stereospecific proton transfer between solvent and the pro-R position of keto-substrate. As a result of an attempt to clarify the physiological importance of oxaloacetate tautomerase activity, keto-oxaloacetate was demonstrated to be directly transported across the inner membrane of rat liver mitochondria on the basis of the results of kinetic and isotope-trapping experiments.
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PMID:Stereochemistry and function of oxaloacetate keto-enol tautomerase. 395 7

The mitochondrial inner membrane lost its selectivity for the transport of solutes after reaction of hydrophobic sulfhydryl groups with alkylating agents (maleimide derivatives). The nature of the thiol reagent-induced membrane perturbations was investigated. Modifications of the interactions between membrane components after treatment with thiol reagents were assessed by measuring the binding parameters of 1-anilinonaphtalene-8-sulfonate. An enhancement (about 50%) of the fluorescence intensity, a weak increase of the number of binding sites, and a decrease of the apparent dissociation constant were observed. However, no significant modification of the net surface charge was detected. The osmotic behavior of mitochondria in hypotonic solutions of sucrose was altered after thiol modification. The outer membrane did not seem to influence the matricial volume expansion when thiols were alkylated. After swelling in an isotonic solution of permeant ions, N-butylmaleimide-treated mitochondrial lost one-half of their malate dehydrogenase content, whereas fumarase and glutamate dehydrogenase did not leave the matrix space. Addition of polyethylene glycol of molecular weight below 6000 to swollen mitochondria induced a rapid but transient shrinkage. In swollen mitochondria, the above results indicate a possible holes formation in the membrane structure. The size of these holes was estimated to be about 3 nm. This process which required the presence of the outer membrane, was favored by increasing the temperature and was antagonized by specific effectors of the adenine nucleotide translocator.
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PMID:Crucial role of sulfhydryl groups in the mitochondrial inner membrane structure. 399 77


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