Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.28 (lactic acid dehydrogenase)
 476 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In Peptostreptococcus elsdenii, a three-component flavoprotein electron transfer system catalyzes the oxidation of lactate and the reduction of crotonyl-coenzyme A (CoA). Spectral evidence showed that D-lactate dehydrogenase, when reduced by D-lactate, was able to reduce butyryl-CoA dehydrogenase, but only in the presence of the electron-transferring flavoprotein. Reduced nicotinamide adenine dinucleotide could replace reduced D-lactate dehydrogenase. A reconstituted system, containing the three partially purified enzymes, excess D-lactate, and a limiting amount of crotonyl-CoA, reduced the crotonyl-CoA to butyryl-CoA, but only if all components were present. The electron-transferring flavoprotein activity, purified 22-fold, was separated into two major flavoprotein components, A and B, after polyacrylamide gel electrophoresis. Elution of the proteins and subsequent kinetic assays of the eluates showed that component B catalyzes the reduction of butyryl-CoA dehydrogenase by reduced D-lactate dehydrogenase, whereas component A does not. Both A and B catalyzed the reduction of butyryl-CoA dehydrogenase by reduced nicotinamide adenine dinucleotide. The results suggest that the D-lactate dehydrogenase-dependent reduction involves a heretofore unrecognized component of the electron-transferring protein group which may utilize an unusual flavin, 6-hydroxy-7,8-dimethyl-10-(ribityl-5'-adenosine diphosphate)-isoalloxazine.
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PMID:Electron-transferring flavoprotein of Peptostreptococcus elsdenii that functions in the reduction of acrylyl-coenzyme A. 17 88

The synthesis of 5-(2-oxalylethyl)-NADH, a reduced nicotinamide adenine dinucleotide (NADH) derivate with pyruvate covalently attached to the 5 position of the dihydronicotinamide ring over an additional methylene group has been described previously (Trommer, W.E., Blume, H., and Kapmeyer, H. (1976) Justus Liebigs Ann. Chem., 848). In the presence of lactate dehydrogenase, the dihydropyridine ring of this coenzyme-substrate analogue is oxidized and the carbonyl function of the side chain is reduced to the corresponding L-hydroxy derivative with a maximum velocity of 1/3000 of the natural reaction. This reaction is intramolecular as shown by competition experiments with pyruvate. 5-(2-oxalylethyl)-NADH (pyr-NADH) appears to be a true transition state analogue, proving its postulated structure. Pyr-NADH is high specific for this enzyme as demonstrated by the facts that (1) D-lactate dehydrogenase does not catalyze the intramolecular redox reaction, although the substrate moiety of pyr-NADH is reduced in the presence of NADH; (2) when tested with malate dehydrogenase, alcohol dehydrogenase, glyceraldehyde phosphate dehydrogenase,glycerate dehydrogenase, and glycerol dehydrogenase pyr-NADH is not even oxidized in the presence of the corresponding substrates. However, a great similarity between the transition states of the reduction of pyruvate catalyzed by lactate dehydrogenase and alanine dehydrogenase could be shown. Alanine dehydrogenase catalyzes the intramolecular redox reaction as well. In the presence of ammonium ions, pyr-NADH is transformed to 5-(3-carboxyl-3-aminopropyl)-NAD+.
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PMID:A transition state analogue for two pyruvate metabolizing enzymes, lactate dehydrogenase and alanine dehydrogenase. 18

An Escherichia coli mutant (tolI) previously shown to be tolerant to colicins Ia and Ib is defective in several functions of the bacterial cytoplasmic membrane. When compared with its parental strain, X36, whole cells of tolI show reduced rates of respiration with succinate, malate, or lactate as the substrate but near-normal rates with glucose or glycerol. Cell membrane preparations prepared from tolI cells exhibit reduced succinate and D-lactate oxidase activity but elevated levels of reduced-form nicotinamide adenine dinucleotide (NADH) oxidase. tolI cells have reduced levels of succinate and D-lactate dehydrogenase but normal levels of NADH dehydrogenase. Glycerol-grown tolI cells and membrane vesicles prepared from such cells are defective in the active transport of several amino acids and thiomethyl-beta-D-galactoside; however, they accumulate higher levels of alpha-methylglucoside when compared with X36 whole cells or vesicles. Although tolI cells adsorb less colicin Ia at high colicin concentrations than do X36 cells, it is shown that the adsorption of an Ia molecule to tolI cells has a lower probability of eliciting cell death than does Ia adsorption to strain X36 cells. It is concluded that a single mutation can lead to an alteration in several aspects of cytoplasmic membrane function and colicin I sensitivity.
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PMID:Alterations in membrane function in an Escherichia coli mutant tolerant to colicins Ia and Ib. 110 88

Using 8-demethyl-8-hydroxy-5-deaza-5-carba analogues of the appropriate flavin nucleotides, we determined the stereochemistry of interaction between coenzyme and substrate for several flavoproteins. The enzymes were D-amino acid oxidase, L-lactate oxidase, and D-lactate dehydrogenase, all three of which interact with pyruvate, as well as cyclohexanone monooxygenase and 2-methyl-3-hydroxypyridine-5-carboxylic acid oxygenase, which were both probed with nicotinamide nucleotides. L-Lactate oxidase and D-lactate dehydrogenase used the si face of the modified flavin ring while the other three enzymes showed re-side specificity. This selection of flavoenzymes includes FAD- and FMN-dependent enzymes, enzymes that follow a carbanion mechanism, and others that have hydride transfer as an integral part of their reaction pathway.
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PMID:Stereochemistry and accessibility of prosthetic groups in flavoproteins. 289 58

A coupled-enzyme assay for determining viral neuraminidase activity is described. All reactants-viral neuraminidase, the initial substrate (fetuin), N-acetylneuraminic acid aldolase, lactic acid dehydrogenase, and reduced nicotinamide adenine dinucleotide-are combined in a single cuvette. Thus, in a single coupled system neuraminidase releases N-acetylneuraminic acid, which is cleaved to N-acetyl-D-mannosamine and pyruvic acid; finally, pyruvate is reduced to lactate as reduced nicotinamide adenine dinucleotide is oxidized. The rate of change of absorbance at 340 nm, as reduced nicotinamide adenine dinucleotide is oxidized, is a measure of the rate of reaction of the coupled system. This procedure, which measures the rate of release of N-acetylneuraminic acid by neuraminidase, is an alternate method for those procedures which require multistep, colorimetric determinations.
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PMID:Coupled-enzyme system for measuring viral neuraminidase activity. 411 35

Effects of exercise regimens on the enzyme histochemical changes of articular chondrocytes of the humeral heads in adult shepherd-type dogs were studied. One group of 4 dogs was exercised by walking on a flat surface 5 days a week for 6 months. A 2nd group of 4 dogs was exercised under the same conditions, except that the dogs were forced to walk over platforms placed in their path. Three control dogs were exercised ad libitum in their housing area. In all dogs, the reactivity of lactic acid dehydrogenase was quite strong nicotinamide dinucleotide dehydrogenase was moderate, and glucose-6-phosphatase was week. Succinic acid dehydrogenase uridine diphosphate (UDP)-galactose-4-epimerase, and UDP-N-acetylglucosamine-4-epimerase were of weakly moderate staining reactivity. Consistent regional or laminar variability was not found among the chondrocytic populations of the exercised and control groups for the reactivity of the enzymes studied. However, regional and/or laminar variabilities in individuals of the experimental groups were identified. The weak reactivity of glucose-6-phosphatase as seemingly contradictory to the presence of intracellular lipids of adult articular chondrocytes. Lipid synthesis was suggested as a mechanism to store excessive quantities of hydrogen ions in an innocuous form, rather than in the potentially deleterious by-product of anaerobic glycolysis, lactic acid.
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PMID:Effects of exercise on the histochemical changes of articular chondrocytes in adult dogs. 680 69

Isolated membranes of the cell wall-less stable protoplast L-form of Proteus mirabilis were characterized by density gradient centrifugation and by assay for their major chemical constituents, proteins, phospholipids and lipopolysacchartide, and for some specific marker enzymes of the cytoplasmic membrane. In most of the analyzed properties the L-form protoplast membrane resembled the bacterial cytoplasmic membrane, with some notable modifications. Considerable amounts of lipopolysaccharide, normally an exclusive constituent of the outer membrane, were found. Furthermore, the L-form membranes contained the functions of the reduced nicotinamide adenine dinucleotide oxidase system, of D-lactate dehydrogenase (EC 1.1.1.28) and of succinate dehydrogenase (EC 1.3.99.1) at specific activities comparable to, or in some cases considerably higher than, those present in cytoplasmic membranes of the bacterial form. Of two peptidoglycan DD-carboxypeptidase/transpeptidases (EC 3.4.17.8 and EC 2.3.2.10). which are normally present in the cytoplasmic membrane of the bacterial form of P. mirabilis, the membrane of the protoplast L-form contained only one. Electron microscopy of thin sectioned L-form protoplasts showed extensive heterogeneity of membraneous structures. In addition to the single membraneous integument, internal membrane-bounded vesicles and multiple stacks of membranes were present, as the result of unbalanced growth and membrane synthesis in the L-form state.
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PMID:Membranes of the protoplast L-form of Proteus mirabilis. 700 76

During attempts to clone the gene coding for the respiratory NADH dehydrogenase of Escherichia coli, two hybrid plasmids were constructed from E. coli chromosomal DNA [Young, I. G., Jaworowski, A., & Poulis, M. I. (1978) Gene 4, 25-36]. One of these plasmids, pIY1, derived from EcoRI-digested chromosomal DNA, was studied in detail and shown to possess the gene coding for the NADH dehydrogenase of the aerobic respiratory chain of E. coli. We now report the characterization of the other hybrid plasmid, pIY2, derived from HindIII-digested chromosomal DNA, and shown that it complements ndh mutants not by virtue of carrying the ndh gene but because it carries the gene coding for the respiratory D-lactate dehydrogenase. Cells carrying this hybrid plasmid overproduce the respiratory D-lactate dehydrogenase in their cell membranes by 15-20-fold with negligible activity appearing in the cytoplasm. This results in an amplification of the levels of the D-lactate oxidase. The amplified D-lactate oxidase activity, coupled with the pyridine nucleotide linked D-lactate dehydrogenase, apparently provides a new pathway for the oxidation of reduced nicotinamide adenine dinucleotide (NADH) in the cell, independent of the respiratory NADH oxidase.
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PMID:Cloning of the gene for the respiratory D-lactate dehydrogenase of Escherichia coli. 704 94

R-2-hydroxy-4-phenylbutyric acid (R-HPBA) is an important intermediate in the manufacture of angiotensin converting enzyme inhibitors. In this work, a recombinant D-lactate dehydrogenase (LDH) was used to transform 2-oxo-4-phenylbutyric acid (OPBA) to R-HPBA, with concomitant oxidation of beta-nicotinamide adenine dinucleotide (NADH) to NAD(+). The cofactor NADH was regenerated by formate dehydrogenase (FDH) present in whole cells of Candida boidinii, which were pre-treated with toluene to make them permeable. The whole cells used in the process were more stable and easier to prepare as compared with the isolated FDH from the cells. Kinetic study showed that the reaction rate was dependent on the concentration of cofactor, NAD(+), and that both R-HPBA and OPBA inhibited the reaction. A novel method for co-immobilization of whole cells and LDH enzyme on cotton cloth was developed using polyethyleneimine (PEI), which induced the formation of PEI-enzyme-cell aggregates and their adsorption onto cotton cloth, leading to multilayer co-immobilization of cells and enzyme with high loading (0.5 g cell and 8 mg LDH per gram of cotton cloth) and activity yield ( > 95%). A fibrous bed bioreactor with co-immobilized cells and enzyme on the cotton cloth was then evaluated for R-HPBA production in fed-batch and repeated batch modes, which gave relatively stable reactor productivity of 9 g/L . h and product yield of 0.95 mol/mol OPBA when the concentrations of OPBA and R-HPBA were less than 10 g/L.
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PMID:Biotransformation of R-2-hydroxy-4-phenylbutyric acid by D-lactate dehydrogenase and Candida boidinii cells containing formate dehydrogenase coimmobilized in a fibrous bed bioreactor. 1603 87

The ability of reduced nicotinamide adenine dinucleotide (NADH), generated through the activity of lactic acid dehydrogenase, to support the reduction of endogenous oxidized glutathione in intact human erythrocytes and in hemolysates was investigated. Rapid initial oxidation of endogenous reduced glutathione was effected with methyl phenylazoformate. Freshly obtained normal erythrocytes and erythrocytes deficient in glucose-6-phosphate dehydrogenase activity were unable to regenerate reduced glutathione upon incubation with lactate. Only normal erythrocytes were capable of reducing oxidized glutathione after preincubation with glucose, inosine, or a medium which promoted the synthesis of increased amounts of intracellular NAD. This regeneration of reduced glutathione could be explained by the generation of reduced nicotinamide adenine dinucleotide phosphate through the metabolism of accumulated phosphorylated intermediates of glycolysis. Hemolysates prepared from both normal erythrocytes and from erythrocytes deficient in glucose-6-phosphate dehydrogenase activity were able to reduce oxidized glutathione in the presence of added lactate and NAD. The results obtained indicated either an inability of the intact erythrocyte to utilize the NAD at the concentrations attained or an altered behavior of the system for the regeneration of reduced glutathione after lysis of the cell.
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PMID:Reduced nicotinamide adenine dinucleotide and the reduction of oxidized glutathione in human erythrocytes. 1669 46


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