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)

It is shown in experiments is vivo that development of experimental metabolic alkalosis in rats is followed by changes in redox processes in the eye retina and tunic. For the first two months of the experiment the number of sulphydryl group decreases, while that of disulphide ones of water-soluble proteins and low-molecular compounds increases. The amount of oxidized metabolites of glycolysis and of a cycle of tricarboxylic acids (pyruvate, oxaloacetate, alpha-ketoglutarate) increases relative to the reduced ones (lactate, isocitrate, malate), as well as activities of hexokinase, pyruvate kinase, NAD-dependent malate dehydrogenase, while activities of fructose diphosphatase, glucoso-6-phosphate dehydrogenase, glutathione peroxidase and glutathione reductase fall. The content of malonic dialdehyde increases. 90 days later disorders of certain compensatory mechanisms of the metabolic system of alkalosis regulation probably occurred in the eye retina and tunic tissues: hexokinase and pyruvate kinase activity fell to the control values, while that of NAD-dependent malate dehydrogenase--below the control level; the content of lactate increased. Activity of glutathione-dependent enzymes remained low and the amount of malonic dialdehyde grew much more than in the previous terms.
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PMID:[Redox processes in the retina and tunic tissues of the rat eye in experimental alkalosis]. 144 Sep 68

Renal clear cell tubules and clear/acidophilic cell tumors were induced in male Sprague-Dawley rats by 7 weeks oral administration (stop model) of N-nitrosomorpholine (NNM) at a concentration of 12 mg/100 ml in the drinking water. Twelve, 23 and 34 weeks after withdrawal of NNM serial cryostat sections of the kidneys were histochemically analyzed for the following parameters: glucose transporter proteins (GLUT1, GLUT2), glycogen content and the activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), glucose-6-phosphate dehydrogenase (G6PDH), hexokinase (HK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PK), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), alkaline phosphatase (ALP), acid phosphatase (ACP) and gamma-glutamyltransferase (GGT). Clear cell (glycogenotic) tubules first appeared at 23 weeks, and clear/acidophilic cell tumors at 34 weeks after withdrawal of the carcinogen. G6Pase, ALP, GGT and GLUT2 were absent in clear cell tubules, clear/acidophilic cell tubules, and clear/acidophilic cell tumors indicating a sequential origin of all these types of lesions from the collecting duct system, in line with previous morphological findings. In comparison to the collecting duct epithelium, glycogenotic tubules demonstrated an increased activity of PHO and reduced activities of glycolytic and mitochondrial enzymes, which were accompanied by a strongly reduced expression of GLUT1. Moderately increased activities of glycolytic and mitochondrial enzymes were observed in the clear cells of clear/acidophilic cell tubules and tumors compared with those in glycogenotic tubules. They had slightly increased activities of the glycolytic enzymes GAPDH and PK compared with normal collecting duct epithelium, while most of them were nearly lacking in GLUT1. Our findings suggest that glycogen storage is not due to an increased uptake of glucose from the blood, but results from a disturbance in intracellular flux of metabolites. The development of clear cell tubules from the normal collecting duct epithelium is accompanied by a markedly decreased expression of GLUT1 along with a reduction in glycolytic and mitochondrial enzymes. This reduction of enzyme activities is replaced by an increase in enzyme activities in clear/acidophilic cell tumors indicating a fundamental shift in carbohydrate metabolism during progression from preneoplastic to neoplastic lesions.
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PMID:Sequential changes in glycogen content, expression of glucose transporters and enzymic patterns during development of clear/acidophilic cell tumors in rat kidney. 147 41

The crystal structure of malate dehydrogenase from Escherichia coli has been determined with a resulting R-factor of 0.187 for X-ray data from 8.0 to 1.87 A. Molecular replacement, using the partially refined structure of porcine mitochondrial malate dehydrogenase as a probe, provided initial phases. The structure of this prokaryotic enzyme is closely homologous with the mitochondrial enzyme but somewhat less similar to cytosolic malate dehydrogenase from eukaryotes. However, all three enzymes are dimeric and form the subunit-subunit interface through similar surface regions. A citrate ion, found in the active site, helps define the residues involved in substrate binding and catalysis. Two arginine residues, R81 and R153, interacting with the citrate are believed to confer substrate specificity. The hydroxyl of the citrate is hydrogen-bonded to a histidine, H177, and similar interactions could be assigned to a bound malate or oxaloacetate. Histidine 177 is also hydrogen-bonded to an aspartate, D150, to form a classic His.Asp pair. Studies of the active site cavity indicate that the bound citrate would occupy part of the site needed for the coenzyme. In a model building study, the cofactor, NAD, was placed into the coenzyme site which exists when the citrate was converted to malate and crystallographic water molecules removed. This hypothetical model of a ternary complex was energy minimized for comparison with the structure of the binary complex of porcine cytosolic malate dehydrogenase. Many residues involved in cofactor binding in the minimized E. coli malate dehydrogenase structure are homologous to coenzyme binding residues in cytosolic malate dehydrogenase. In the energy minimized structure of the ternary complex, the C-4 atom of NAD is in van der Waals' contact with the C-3 atom of the malate. A catalytic cycle involves hydride transfer between these two atoms.
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PMID:Crystal structure of Escherichia coli malate dehydrogenase. A complex of the apoenzyme and citrate at 1.87 A resolution. 150 30

Analysis of the mechanism and structure of lactate dehydrogenases is summarized in a map of the catalytic pathway. Chemical probes, single tryptophan residues inserted at specific sites and a crystal structure reveal slow movements of the protein framework that discriminate between closely related small substrates. Only small and correctly charged substrates allow the protein to engulf the substrate in an internal vacuole that is isolated from solvent protons, in which water is frozen and hydride transfer is rapid. The closed vacuole is very sensitive to the size and charge of the substrate and provides discrimination between small substrates that otherwise have too few functional groups to be distinguished at a solvated protein surface. This model was tested against its ability to successfully predict the design and synthesis of new enzymes such as L-hydroxyisocaproate dehydrogenase and fully active malate dehydrogenase. Solvent friction limits the rate of forming the vacuole and thus the maximum rate of catalysis.
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PMID:Design and synthesis of new enzymes based on the lactate dehydrogenase framework. 167 37

Zidovudine (azidothymidine (AZT)) inhibits human immunodeficiency virus replication, prolongs survival, and delays progression of acquired immune deficiency syndrome. We determined AZT-induced molecular and ultrastructural changes in the rat heart. Rats (3 per group) were given drinking water with or without AZT (0.2 to 1.0 mg/ml; 29 to 102 mg/kg/day). After 21, 35, or 49 days, hearts were glutaraldehyde-fixed by abdominal aortic perfusion, processed, and examined by transmission electron microscopy. In parallel, myocardial RNA was extracted from hearts (AZT dose: 1 mg/ml; 35 days) and subjected to Northern analysis using cDNA probes for: alpha c-actin, troponin C, mitochondrial creatine kinase and malate dehydrogenase, a portion of the mitochondrial genome containing cytochrome b coding region (pMM26), and glyceraldehyde-3-phosphate dehydrogenase. Results showed marked and widespread cardiac mitochondrial swelling with fractured and disrupted cristae after 35 days of 1 mg/ml AZT. After a 14-day recovery, these ultrastructural defects did not reverse. Changes were not present in myocardium after 21 days of AZT nor after 35 days of lower dose AZT (0.2 mg/ml). Mitochondrial cytochrome b mRNA expression was depressed in AZT-treated rat hearts (35 days; 1 mg/ml AZT). mRNAs encoding glyceraldehyde-3-phosphate dehydrogenase, alpha c-actin, troponin C, mitochondrial creatine kinase, malate dehydrogenase, and mitochondrial ribosomal RNAs remained unchanged. AZT disrupts cardiac mitochondrial ultrastructure and expression of mitochondrial cytochrome b mRNA in a dose- and time-dependent fashion. The mechanism of AZT cardiotoxicity may relate to inhibition of mitochondrial DNA replication (at the level of DNA polymerase gamma) as postulated by others.
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PMID:Mitochondrial ultrastructural and molecular changes induced by zidovudine in rat hearts. 171 47

A supramaximal dose of caerulein (5 micrograms/kg.hr for 3.5 hours) caused edematous acute pancreatitis in rats, characterized by portal hyperamylasemia (32 +/- 3 U/ml) and pancreatic edema (pancreatic water content, 86 +/- 2%) [control group: amylase, 8 +/- 1 U/ml; water content, 74 +/- 2%]. In this model, increased portal levels of malate dehydrogenase (148 +/- 25 U/ml), increased mitochondrial fragility and impaired pancreatic energy charge level (0.77 +/- 0.05) were also observed [control group: malate dehydrogenase, 54 +/- 11 U/ml; energy charge level, 0.94 +/- 0.03]. Administration of gabexate mesilate, FOY, in a dose of 50 mg/kg.hr for 2 hours before and during the caerulein infusion had a significant protective effect against these pancreatic injuries (portal amylase level, 11 +/- 2 U/ml; MDH level, 72 +/- 19 U/ml; E.C., 0.89 +/- 0.02; water content, 76 +/- 2%). FOY in a dose of 20 mg/kg.hr was partially protective. These results indicate that subcellular organelle fragility and malfunction are closely related to the pathogenesis of acute pancreatitis and suggest the usefulness of FOY in the treatment of this disease.
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PMID:Protective effects of gabexate mesilate (FOY) against impaired pancreatic energy metabolism in rat acute pancreatitis induced by caerulein. 171 26

The activity, stability and structure in solution of polypeptide elongation factor hEF-Tu from Halobacterium marismortui have been investigated. The protein is stable in aqueous solutions only at high concentrations of NaCl, KCl or ammonium sulphate, whereas it is more active in exchanging GDP at lower salt concentrations. It is more active and stable at lower pH values than is non-halophilic EF-Tu. The structure in solution of the protein was determined by complementary density, ultracentrifugation, dynamic light-scattering and neutron-scattering measurements. The protein has large hydration interactions, similar to those of other halophilic proteins: 0.4 (+/- 0.1) g of water and 0.20 (+/- 0.05) g of KCl associated with 1 g of protein, with a water/KCl mass ratio always remaining close to 2. The kinetics of inactivation at low salt concentrations showed a stabilizing effect of NaCl when compared to KCl. At low salt concentration, inactivation, protein unfolding and aggregation were strongly correlated. The results suggest that the stabilization model proposed for halophilic malate dehydrogenase by Zaccai et al., involving extensive protein interactions with hydrated salt ions, is also valid for hEF-Tu.
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PMID:Solution studies of elongation factor Tu from the extreme halophile Halobacterium marismortui. 173 Oct 81

The conjugates of glucose-6-phosphate dehydrogenase, lactate dehydrogenase, and malate dehydrogenase with progesterone and cortisol, containing 1-40 steroid molecules per enzyme molecule, were obtained by the reactions of N-succinimide esters of the 3-[O-(carboxymethyl)oximes)] of cortisol and progesterone with a protein in a water-DMFA (10%) medium. The catalytic activity and thermostability of dehydrogenases and their steroid conjugates were kinetically studied. The effects of the modification degree on the activity and thermostability of dehydrogenases by their hydrophobization were studied and discussed. Practical recommendations for using the dehydrogenase-steroid conjugates in enzyme immunoassay are given.
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PMID:Catalytic activity and thermostability of dehydrogenase conjugates with cortisol and progesterone. 179 Jan 69

Prolonged exposure to hexacarbon compounds is neurotoxic to humans and animals. As various hexacarbon compounds inhibit glycolytic enzymes in vitro, it has been suggested that this may underlie their neurotoxic effects in vivo. In the present investigation we examined whether long-term treatment with 2,5-hexanedione (200 mg/kg,sc) for 40 days affects the specific activity of brain and liver enolase, lactic dehydrogenase and malate dehydrogenase in female Wistar rats (150-170 g). Glycemia and liver glycogen levels were also determined. The specific activity of all enzymes tested, liver glycogen content and glycemia were not affected by chronic treatment with 2,5-hexanedione. Rats treated with 2,5-hexanedione weighed significantly less than control rats starting on day 18 of treatment (183 +/- 3.4 g for the vehicle group vs 171 +/- 3.2 g for the 2,5-hexanedione group). 2,5-Hexanedione also increased water intake (46% when compared to vehicle-treated rats). Prolonged treatment of rats with the non-neurotoxic hexacarbon 1,6-hexanediol (207 mg/kg, sc) significantly increased liver glycogen content (5.9 +/- 0.6 g/100 g for the vehicle group vs 9.0 +/- 1.1 g/100 g for the 1,6-hexanediol group) as well as food intake (44.0 +/- 1.5 g 100 g-1 6 days-1 for the vehicle vs 50.0 +/- 1.1 g 100 g-1 6 days-1 for the 1,6-hexanediol group).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term treatment with 2,5-hexanedione has no effect on the specific activity of some brain and liver glycolytic enzymes of adult rats. 182 91

We report here on the Raman spectra of NADH, 3-acetylpyridine adenine dinucleotide, APAD+, and a fragment of these molecules, adenosine 5'-diphosphate ribose (ADPR) bound to the mitochondrial (mMDH) and cytoplasmic (or soluble, sMDH) forms of malate dehydrogenase. We observe changes in the Raman spectrum of the adenosine moiety of these cofactors upon binding to mMDH, indicating that the binding site is hydrophobic. On the other hand, there is little change in the spectrum of the adenosine moiety when it binds to sMDH. Such observations are in clear contrast with those results obtained in LDH and LADH, where there are significant changes in the spectrum of the adenosine moiety when it binds to these two proteins. A strong hydrogen bond is postulated to exist between amide carbonyl group of NAD+ and the enzyme in the binary complexes with both mMDH and sMDH on the basis of a sizable decrease in the frequency of the carbonyl double bond. The interaction energy for formation of a hydrogen bond is the same as found previously for LDH, and we estimate that it is 2.8 kcal/mol more favorable in the binary complex than in water. A hydrogen bond is also detected between the amide-NH2 group of NADH and sMDH that is stronger than that formed in water and is of the same size as found in LDH. Surprisingly, the hydrogen bond to the -NH2 group in mMDH is the same as that found for water.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Raman spectroscopic studies of NAD coenzymes bound to malate dehydrogenases by difference techniques. 188 40


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