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 first enzymatic method involving enzmatic cycling for the assay of a synthetic steroid, medroxyprogesterone acetate (MPA), in plasma is reported. First the steroid is extracted and chromatographically purified, and then it is desacetylated and rechromatographed on the same Lipidex column. The primary enzymatic reaction is carried out with 3 alpha, 20 beta-hydroxy-steroid dehydrogenase and the nicotinamide adenine dinucleotide+ product formed is enzymatically cycled with alcohol dehydrogenase and malate dehydrogenase. Malate, the product formed, is measured in a third enzymatic step with malate dehydrogenase in a medium of glutamate oxaloacetic transaminase. The reduced nicotinamide is measured fluorometrically. The final fluorometric assay's sensitivity is 25-30 fmol. Using 250-mcliter samples, the assay can detect MPA at a level of .6-1 nmol per liter of plasma.
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PMID:Enzymatic assay of medroxyprogesterone acetate in plasma. 699 91

The author carried out a dynamic study on the metabolic changes in liver under the influence of nicotinic acid, administered singly by intramuscular injection in a dose of 2mM/kg of body weight. She examined at the 1th, 3th, 6th and 24th hour the changes in the levels of nicotine-amide coenzymes (NAD, NAD-H and NADP), adenine nucleotides (ATP, ADP and AMP), the metabolic lactate and pyruvate and the enzymes LDH, MDH, GOT and GPT. The obtained data were compared with those of the control groups, treated with saline and killed at the same intervals as the experimental animals. Furthermore she made also a comparison with an intact group, presented as O group, whose values served as basal. The obtained data showed that after application of the nicotinic acid (NA) complex metabolic changes occurred in liver, due to its basic effects-stimulation of biosynthesis of nicotinamide coenzymes and inhibition of lipolysis in the fatty tissue. Most probably the effect on the biosynthesis of NAD was primary, which showed later substantial regulatory influence both on lipolysis in the fatty acid and on the metabolization of mobilizing lipids on behalf of the liver. Parallel occurring metabolic processes in the aorta and in the vascular wall in general, stimulation of the biological oxidation and bioenergetics formed the whole antilipolytic and antiarteriogenic action of nicotinic acid.
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PMID:[Metabolic changes in the liver as affected by nicotinic acid]. 730 22

Study of the key mechanisms, metabolism regulators, showed that in the blood of patients with atherosclerosis the NAD/NAD . N ratio decreases by 59.8% and the NAD+ concentration by 44%, while the NAD . N content increases by 56.7%. In the nicotinamide adenine dinucleotide system there is a general tendency tomards accumulation:the concentration of NADP+ grows by 218.6% and that of NADP . N by 12.9%. A marked increase in the content of incompletely oxidized products is determined: lactic acid by 37.4%, alpha-glycerophosphate by 49.8%, dihydroxyacetone phosphate by 155%, oxaloacetate by 131% in the presence of lactate dehydrogenase and malate dehydrogenase activation. The detected changes are evidence of tissue energy debt in atherosclerosis, they reflect the character of metabolic acidosis formation and point to the presence of conditions for intensified liposynthesis.
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PMID:[Content of nicotinamide coenzymes, metabolites and the NAD-dependent dehydrogenase activity in the blood in arteriosclerosis]. 737 12

The biochemical and cytotoxic activities of the IMP dehydrogenase (IMPDH) inhibitors benzamide riboside, tiazofurin, and selenazofurin were compared. These three C-nucleosides exert their cytotoxicity by forming an analogue of NAD, wherein nicotinamide is replaced by the C-nucleoside base. The antiproliferative activities of these three agents were compared in a panel of 60 human cancer cell lines. To examine the relationship of benzamide riboside and selenazofurin to tiazofurin, COMPARE computer analysis was performed, and correlation coefficients of 0.761 and 0.815 were obtained for benzamide riboside and selenazofurin, respectively. The biochemical activities of these agents were examined in human myelogenous leukemia K562 cells. Incubation of K562 cells for 4 hr with 10 microM each of benzamide riboside, selenazofurin and tiazofurin resulted in a 49, 71, and 26% decrease in IMPDH activity with a concurrent increase in intracellular IMP pools. As a consequence of IMPDH inhibition, GTP and dGTP concentrations were curtailed. These studies demonstrated that selenazofurin was the most potent of the three agents. To compare the cellular synthesis of NAD analogues of these agents, K562 cells were incubated with 10 microM each of benzamide riboside, tiazofurin and selenazofurin after prelabeling the cells with [2,8-3H]adenosine. The results demonstrated that benzamide riboside produced 2- and 3-fold more of NAD analogue (BAD) than tiazofurin and selenazofurin did. To elucidate the effects of the three compounds on other NAD-utilizing enzymes, the inhibitory activities of purified benzamide adenine dinucleotide (BAD), thiazole-4-carboxamide adenine dinucleotide (TAD) and selenazole-4-carboxamide adenine dinucleotide (SAD) were studied in commercially available purified preparations of lactate dehydrogenase, glutamate dehydrogenase and malate dehydrogenase. TAD and SAD did not inhibit these three dehydrogenases. Although BAD did not influence lactate and glutamate dehydrogenases, it selectively inhibited 50% of malate dehydrogenase activity at a 3.2 microM concentration. These studies demonstrate similarities and differences in the biochemical actions of the three C-nucleosides, even though they share similar mechanisms of action.
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PMID:Comparison of biochemical parameters of benzamide riboside, a new inhibitor of IMP dehydrogenase, with tiazofurin and selenazofurin. 794 41

Micro-determination methods were used for quantitative examination of possible differences in energy metabolism in mouse embryos arising after spontaneous ovulation or after gonadotrophin stimulation. Comparisons of embryonic development in vivo and in vitro were also made. The relevance of the results to human development and their clinical significance are discussed. The enzymatic activity of hexokinase, phosphofructokinase, glucose 6-phosphate dehydrogenase, malate dehydrogenase and lactate dehydrogenase in individual mouse embryos throughout preimplantation development was evaluated. Hexokinase activity in 1-cell embryos was the lowest by far of the five enzymes measured, and the 0.035 +/- 0.010 pmol of nicotinamide adenine dinucleotide phosphate hydrogenase formed/embryo/min was also lower than in any of the somatic organs examined. Hexokinase activity, unlike the other enzymes, progressively increased in the morulae and blastocyst stages in embryos obtained either by spontaneous ovulation or via gonadotrophin stimulation. Although there is a significant delay, this increase was also observed when 2-cell embryos developed in vitro. Increases in hexokinase activity were observed 68-75 h after human chorionic gonadotrophin administration in vivo, but after 80-86 h in vitro. These increases in vitro were inhibited by the administration of actinomycin D added to the medium. The results suggest that hexokinase may be a key enzyme synthesized as the zygotic genome is expressed in preimplantation embryos, and its measurement may help to assess the quality of embryos developed in vitro.
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PMID:Hexokinase activity in mouse embryos developed in vivo and in vitro. 802 95

The structure of malate dehydrogenase from Escherichia coli complexed with the substrate analog, citrate and the cofactor NAD, has been determined by X-ray crystallography. A monoclinic crystal of the malate dehydrogenase, grown in citrate buffer, was soaked in 10 mM NAD solution and found to be isomorphous with the apo-form. The X-ray data extended to 1.9 A, nearly the same resolution limit as the apo-enzyme crystals. The ternary complex of malate dehydrogenase has very few conformational differences from that of the pseudo binary complex of enzyme with bound citrate. In addition, the NAD molecule has a very similar conformation to the NAD as found in the crystal structure of the cytosolic eukaryotic malate dehydrogenase. Similar hydrogen bond interactions are made by both enzymes from polar groups belonging to the NAD. Such interactions include hydrogen bonds from the ribose oxygens and the phosphate oxygens, to backbone amide and carbonyl atoms of the protein and to side-chains of a select few conserved hydrophilic residues. The only notable difference occurs in the active site region where the nicotinamide moiety is obstructed from further entering the active site by the C-6 carbonyl atoms of citrate. In this position there are no direct polar interactions between the protein and the nicotinamide moiety. Energy minimization of the structure with malate substituted for citrate in the active site shows that the nicotinamide moiety assumes the same position in the active site as the NAD in cytosolic malate dehydrogenase. The carboxamide atoms of the energy minimized model make significant hydrogen bond interactions with the catalytic residue, H177, and with the main-chain atoms of I117 and V146 in the vicinity of the active site, while the position of the rest of the cofactor remains unchanged.
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PMID:Crystal structure of a ternary complex of Escherichia coli malate dehydrogenase citrate and NAD at 1.9 A resolution. 833 58

Seven biomimetic anthraquinone triazinyl dye-ligands, bearing as triazine-linked terminal moiety (keto)carboxylated structures mimicking substrates and inhibitors of malate dehydrogenase (MDH), were immobilised on cross-linked agarose Ultrogel A6R. These biomimetic ligands are terminal-ring analogues of commercial nonbiomimetic Cibacron blue 3GA (CB3GA) and parent Vilmafix blue A-R (VBAR). The biomimetic-dye adsorbents, along with nonbiomimetic adsorbents bearing immobilised CB3GA and VBAR, were evaluated for their ability to purify mitochondrial malate dehydrogenase (mMDH) from bovine heart. All but two biomimetic-dye adsorbents displayed higher purifying ability for MDH, compared to nonbiomimetic-dye adsorbents. Furthermore, immobilised anthraquinone-dyes were able to discriminate between the mitochondrial and the cytoplasmic MDH isoenzymes, binding only to the former. One immobilised biomimetic-dye (BM5), bearing as biomimetic terminal moiety 4-aminophenyloxanylic acid, showed the highest purifying ability. This affinity adsorbent was exploited in the purification of mMDH from unpretreated bovine heart extract in one-step. The procedure afforded mMDH at 54% overall yield and of specific activity approx. 1300 U mg-1 (25 degrees C), using step-elution with a mixture containing 0.1 mM beta-nicotinamide adenine dinucleotide (NAD+) and 1.5 mM sulphite. Commercial analytical-grade bovine heart mitochondrial MDH, when assayed under identical conditions, gave a specific activity not exceeding 950 U mg-1. The well-known adsorbent Cibacron blue 3GA-agarose exhibited 8% lower recovery and 25% lower purification for mMDH. The product obtained from the procedure based on the BM5-adsorbent was free of cytoplasmic MDH, glutamic-oxaloacetic transaminase (GOT) and fumarase, and since it has also shown high specific activity, it should be suitable for analytical applications.
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PMID:Biomimetic-dye affinity chromatography for the purification of mitochondrial L-malate dehydrogenase from bovine heart. 872 5

Recently a new tetrazolium was described for the use of monitoring cell viability in culture. This tetrazolium, commonly referred to as MTS [3-(4,5-dimethylthiazol-2-yl)- 5-(3-carboxymethonyphenol)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt], has the unusual property that it can be reduced to a water-soluble formazan. beta-Nicotinamide adenine dinucleotide/reduced (NADH) and beta-nicotinamide adenine dinucleotide phosphate/reduced (NADPH) are examples of physiologically important reducing agents. In cell-free studies, MTS was reduce to the soluble formazan in the presence of NADH and NADPH, and reaction were compared to those with dithiothreitol (DTT) or 2-mercaptoethanol (2-ME). The efficiency of these reactions was enhanced 1000-fold by the presence of phenazine methosulfate. Selectivity in the electron transfer from NADPH was slightly greater than NADH, and NADPH or NADH was much greater than the thiols DTT or 2-ME. Generation of either NADH or NADPH in solution by malate dehydrogenase or isocitrate dehydrogenase, respectively, was monitored by the MTS reduction reaction. The rate of formazan formation was comparable to the formation of NADH or NADPH. This system represents a useful tool for evaluating reaction kinetics in solutions of NAD- or NADP-dependent dehydrogenase enzymes, and these reactions can be performed in typical biological buffers containing reducing agents without significant interference to the MTS/formazan system.
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PMID:Aqueous soluble tetrazolium/formazan MTS as an indicator of NADH- and NADPH-dependent dehydrogenase activity. 877 59

Histochemistry studies of key dehydrogenases in the glycolytic pathway and related enzymes and the tricarboxylic acid (TCA)-cycle enzymes were carried out on adult female Onchocerca fasciata. The distribution pattern and enzymatic activities of 6-phosphogluconate dehydrogenase (6-GPDH), lactate dehydrogenase (LDH), mitochondrial glycerol-3-phosphate dehydrogenase (GPDH), nicotinamide adenine dinucleotide (phosphate) [NAD+(P)]-linked isocitrate dehydrogenase (ICDH), and NAD+(P)-linked malate dehydrogenase (MDH) in various tissues of the worm were determined. Moderate to intense enzyme activities were localized in three main areas, namely, the hypodermis, body-wall muscle, and reproductive tissues. Activity of the formazan reaction product was very low, if at all present, in the intestinal epithelium and was completely absent in the cuticle. On the basis of the present results and earlier observations, it is suggested that glycolysis leading to the end product lactate is the main energy-generating pathway in O. fasciata. The presence of significant activity of 6-GPDH indicates that the pentose-phosphate pathway might be operative in O. fasciata. In light of the activity of some of the TCA-cycle enzymes, ICDH and MDH, demonstrable in O. fasciata, it is possible that an additional pathway (pyruvate-succinate) of glucose metabolism via a reverse sequence of the TCA cycle may also be operative in the worm. The possible functional significance of the enzymes detected is discussed with respect to their location.
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PMID:Onchocerca fasciata: enzyme histochemistry and tissue distribution of various dehydrogenases in the adult female worm. 882 42

A hybrid numerical method, which employs molecular mechanics to describe the bulk of the solvent-protein matrix and a semiempirical quantum-mechanical treatment for atoms near the reactive site, was utilized to simulate the minimum energy surface and reaction pathway for the interconversion of malate and oxaloacetate catalyzed by the enzyme malate dehydrogenase (MDH). A reaction mechanism for proton and hydride transfers associated with MDH and cofactor nicotinamide adenine dinucleotide (NAD) is deduced from the topology of the calculated energy surface. The proposed mechanism consists of (1) a sequential reaction with proton transfer preceding hydride transfer (malate to oxaloacetate direction), (2) the existence of two transition states with energy barriers of approximately 7 and 15 kcal/mol for the proton and hydride transfers, respectively, and (3) reactant (malate) and product (oxaloacetate) states that are nearly isoenergetic. Simulation analysis of the calculated energy profile shows that solvent effects due to the protein matrix dramatically alter the intrinsic reactivity of the functional groups involved in the MDH reaction, resulting in energetics similar to that found in aqueous solution. An energy decomposition analysis indicates that specific MDH residues (Arg-81, Arg-87, Asn-119, Asp-150, and Arg-153) in the vicinity of the substrate make significant energetic contributions to the stabilization of proton transfer and destabilization of hydride transfer. This suggests that these amino acids play an important role in the catalytic properties of MDH.
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PMID:Simulation of the enzyme reaction mechanism of malate dehydrogenase. 912 1


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