Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.27 (lactate dehydrogenase)
 29,211 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The structures of NADP+ and magnesium isocitrate bound to the NADP(+)-dependent isocitrate dehydrogenase of Escherichia coli have been determined and refined at 2.5-A resolution. NADP+ is bound by the large domain of isocitrate dehydrogenase, a structure that has little similarity to the supersecondary structure of the nucleotide-binding domain of the lactate dehydrogenase-like family of nucleotide-binding proteins. The coenzyme-binding site confirms the fundamentally different evolution of the isocitrate dehydrogenase-like and the lactate dehydrogenase-like classes of nucleotide-binding proteins. In the magnesium-isocitrate complex, magnesium is coordinated to the alpha-carboxylate and alpha-hydroxyl oxygen of isocitrate in a manner suitable for stabilization of a negative charge on the hydroxyl oxygen during both the dehydrogenation and decarboxylation steps of the conversion of isocitrate to alpha-ketoglutarate. The metal ion is also coordinated by aspartate side chains 283' (of the second subunit of the dimer) and 307 and two water molecules in a roughly octahedral arrangement. On the basis of the geometry of the active site, the base functioning in the dehydrogenation step is most likely aspartate 283'. E. coli isocitrate dehydrogenase transfers a hydride stereospecifically to the A-side of NADP+, and models for a reactive ternary complex consistent with this stereospecificity are discussed.
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PMID:Catalytic mechanism of NADP(+)-dependent isocitrate dehydrogenase: implications from the structures of magnesium-isocitrate and NADP+ complexes. 188 29

Microcystin-LR (MCLR) is a potent cyclic heptapeptide hepatotoxin produced by the blue-green algae, Microcystis aeruginosa. Toxic blooms of this cyanobacteria have been reported throughout the temperate world. In spite of the potential economic loss and health hazard posed by this toxin, few studies on the development of an antidote have been conducted. Thus, a number of biologically active compounds were tested in mice for effectiveness in preventing the toxicity of a lethal dose of MCLR (100 micrograms kg-1). Efficacy was evaluated based upon the percentage of surviving mice, time to death and serum lactate dehydrogenase activity 45 min after treatment with the toxin. The biologically active compounds were separated into groups based upon proposed mechanisms of action. Enzyme induction by phenobarbital but not by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in partial protection against toxicity. Calcium channel blockers, free-radical scavengers and water-soluble antioxidants produced little protection against toxicity. The membrane-active antioxidants vitamin E and silymarin, as well as glutathione and the monoethyl ester of glutathione, produced significant protection from lethality. Rifampin and cyclosporin-A, both immunosuppressive and membrane-active agents, which also block the bile acid uptake system of hepatocytes, produced complete protection from the toxicity of MCLR. Thus, lipophilic antioxidants provide partial protection against MCLR toxicity while cyclosporin-A and rifampin are highly effective and potentially useful antidotes. The toxicity of MCLR may depend upon stimulation of the immune system and may be mediated by membrane alterations.
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PMID:Evaluation of potential chemoprotectants against microcystin-LR hepatotoxicity in mice. 190 96

S-adenosyl-L-homocysteine hydrolase (AdoHcy hydrolase, EC 3.3.1.1), a specific target for antiviral drug design, catalyzes the hydrolysis of AdoHcy to adenosine (Ado) and homocysteine (Hcy) as well as the synthesis of AdoHcy from Ado and Hcy. The enzyme isolated from different sources has been shown to contain tightly bound NAD+. Based on the 2.0 A-resolution X-ray crystal structure of dogfish lactate dehydrogenase (LDH), which is functionally homologous to AdoHcy hydrolase, and the primary sequence of rat liver AdoHcy hydrolase, we have derived a molecular model of an extended active site for AdoHcy hydrolase. The computational mutation was performed using the software MUTAR (Yeh et al., University of Kansas, Lawrence), followed by molecular mechanics optimizations using the programs AMBER (Singh et al., University of California, San Francisco) and YETI (Vedani, University of Kansas). Solvation of the model structure was achieved by use of the program SOLVGEN (Jacober, University of Kansas); 56 water molecules were explicitly included in all refinements. Some of these may be involved in the catalytic reaction. We also studied a model of the complex of AdoHcy hydrolase with NAD+, as well as the ternary complexes of the enzyme, NAD+, and substrate or inhibitor molecules. Our refined model is capable of explaining part of the redox reaction catalyzed by AdoHcy hydrolase and has been used to differentiate the relative binding strength of inhibitors.
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PMID:A molecular model for the active site of S-adenosyl-L-homocysteine hydrolase. 191 18

Twelve consecutive patients with a solitary functioning kidney were treated for renal stone by extracorporeal shock wave lithotripsy (ESWL*) with the modified Dornier HM3 lithotriptor and studied for 3 days after treatment. Urinary excretion of electrolytes, N-acetyl-beta-glucosaminidase (NAG), alkaline phosphatase, kallikrein, glycosaminoglycans, albumin and beta 2-microglobulin, and clearances of creatinine, inulin and para-aminohippuric acid were determined, as were serum levels of creatinine, urea, beta 2-microglobulin and aldosterone, and plasma renin activity. Urinary flow rate, free water clearance, and urinary excretion of NAG, kallikrein and beta 2-microglobulin were significantly increased 0 to 24 hours after ESWL. The urinary excretions of alkaline phosphatase, albumin and glycosaminoglycans were unchanged. Glomerular filtration rate was significantly decreased and effective renal plasma flow was unchanged. Filtration fraction was stable. Serum lactic dehydrogenase increased significantly after ESWL and remained high through the period of observation. Serum levels of creatinine, beta 2-microglobulin and aldosterone were unaltered. A decrease in plasma renin activity immediately after treatment is explained by the water immersion and the extracellular volume expansion during treatment.
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PMID:Acute changes in renal function following extracorporeal shock wave lithotripsy in patients with a solitary functioning kidney. 198 13

Seventeen patients were subjected to analysis of various renal functional parameters before and after extracorporeal shock wave lithotripsy (ESWL) for renal stones. Thirteen patients were observed at 2 weeks and 3 months. Glomerular filtration rate (GFR) was not influenced by ESWL as based on unchanged serum levels of creatinine, beta 2-microglobulin and creatinine clearance. A significant increase in urinary excretion of beta 2-microglobulin, N-acetyl-beta-glucosaminidase and alkaline phosphatase, with return to pre-treatment values within 4 to 5 days, reflected transient disturbances in proximal tubular function. Urinary albumin excretion was increased 0-24 h after ESWL. No significant alterations were observed in plasma renin activity or serum aldosterone due to ESWL. Serum lactic dehydrogenase remained significantly increased for 2 weeks. In addition, significant changes in several blood and urine parameters were caused by immersion in water and intravenous infusions during treatment and were not specifically due to ESWL.
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PMID:Acute changes in kidney function following extracorporeal shock wave lithotripsy for renal stones. 202 7

An attempt was made to compare the toxic effects of the organochlorine insecticide 'chlordane' in man and rats. Analysis of blood for chlordane metabolites showed their presence in the descending order of trans-nonachlor, oxychlordane, heptachlorepoxide and cis-nonachlor. The total range of chlordane and its metabolites in the sera of workers was 9.84 +/- 4.47 ng/g. Serum levels of triglycerides (TG), creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) activities were also found to be higher in pest-control operators. In a simultaneous study, rats were administered 100 mg/kg body wt. of chlordane by stomach tube once a day for 4 days, whereas 50 mg/kg body wt. of chlordane was injected intraperitoneally once a day for 4 days. The data show that total cholesterol and serum TG as well as CPK and LDH activities are increased after chlordane treatment. The isoenzyme patterns suggest that an increase in CPK and LDH is related to skeletal muscle. Furthermore, the hepatotoxicity of chlordane was also studied in rats only. A significant increase in liver weight, its water content, total lipids, triglycerides and phospholipids was recorded. Chlordane induced lipid peroxidation in the liver, exhibiting a dose-response relationship. Although no appreciable effect on mitochondrial function and latent ATPase activity was observed, 2,4-dinitrophenol-stimulated ATPase activity was inhibited. Histological examination of the liver confirmed fatty infiltration induced by chlordane in rats.
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PMID:Effects of chlordane on parameters of liver and muscle toxicity in man and experimental animals. 203 78

Hepatic cell injury was studied in an in vitro system using rat liver slices incubated in two stages. During the first 2 hr slices were exposed to 10 mM paracetamol, this was absent during the subsequent 4 hr of incubation. Cell damage was quantified at the end by measuring leakage of lactic dehydrogenase, increase in water content and potassium loss. Treatment of slices with 20 mM fructose in the second period of incubation prevented paracetamol-induced damage. The effect of fructose was not modified by the continued presence of paracetamol in the second incubation period. The inhibition of glycolysis either with 1 mM NaF or 10 microM iodoacetate blocked the effect of fructose. The protective effect afforded by fructose was not duplicated by the addition of lactate. All these findings strongly suggest an increase in intracellular ATP levels as the most probable explanation for the protective effect of fructose, and point to fructose as a potentially useful therapeutic tool for protection of the liver late in paracetamol intoxication.
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PMID:Prevention of paracetamol-induced liver injury by fructose. 203 39

Development of improved hydrogels for soft intraocular lenses, based on 2-hydroxyethyl methacrylate monomer, requires the use of various other monomers and polymerization additives which have potential ocular toxicity. Three monomers, 2-hydroxyethyl methacrylate, methyl methacrylate, and 2-ethoxyethyl methacrylate, as well as two common inhibitors, hydroquinone and 4-methoxyphenol, were subjected to in vitro cytotoxicity assays as aqueous solutions at different concentrations. A new polymerization initiator, 2,2'-azo-bis-(2,4-dimethyl valeronitrile), was thermally decomposed in water at different concentrations and the products were also assayed for cytotoxicity. Assays were based on incubation with human choroidal fibroblasts. Cell death was evaluated by trypan blue dye exclusion, DNA synthesis inhibition, and lactate dehydrogenase tests. While methyl methacrylate and 2-ethoxyethyl methacrylate were found nontoxic, the other chemicals displayed high cytotoxicity. However, when extracts of synthesized poly(2-hydroxyethyl methacrylate) specimens, differentially treated after polymerization, were subjected to the same assays it was found that toxicity from residual 2-hydroxyethyl methacrylate monomer was lost during steam sterilization and storage in water because of the removal of the monomer through aqueous washing. The lack of toxicity in these specimens suggests that residual contents of inhibitor and initiator are too low to cause toxic effects on choroidal fibroblasts. It is concluded that hydrogels have low cytotoxic effects in vitro.
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PMID:Cytotoxic effects of residual chemicals from polymeric biomaterials for artificial soft intraocular lenses. 204 Sep 72

Polyacrylamide gel electrophoresis of the two digenetic trematodes, Gigantocotyle explanatum from the liver and Gastrothylax crumenifer from the rumen of the water buffalo, Bubalus bubalis revealed the presence of at least six and seven isoenzymes of lactate dehydrogenase (LDH), respectively in a partially purified enzyme preparation. The respective host tissues showed five isoenzymes of LDH, which are characteristic to the vertebrates. Both parachloromercuribenzoate and iodoacetate affected the LDH activity of the parasites and host tissues differently. Spectrophotometric analysis also showed different specific activity and susceptibility to the action of thiol inhibitors. The host LDH was quite stable at 57 degrees C for 30 min, but that of the parasites was less stable.
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PMID:Lactate dehydrogenase in two digenetic trematodes and their host. 207 42

Serum activities of alanine-aminotransferase (ALAT, EC 2.6.1.2), aspartate-aminotransferase (ASAT, EC 2.6.1.1), lactate dehydrogenase (LDH, EC 1.1.1.27), and alkaline phosphatase (AP, EC 3.1.3.1) were increased significantly after a dose of 0.16 g/kg/b. w. (ip.) carbon tetrachloride (tetrachloromethane) in rats pretreated with 10% (v/v) ethanol for one and 10 weeks in comparison with water/carbon tetrachloride-treated animals. At the end of 30 and 52 weeks of ethanol consumption these levels were very slightly increased or not detectable. Ethanol treatment alone did not cause an increase in serum enzyme activities or histological liver damage, but caused a diminished intake of fluid and food and in some cases also a reduction of weight gain in the animal body. Significant decrease in body weight after carbon tetrachloride was more evident in rats pretreated with ethanol (1 week greater than 10 greater than or equal to 52 weeks) than in water drinking animals, the lethality caused by carbon tetrachloride was also higher after one and 10 weeks than after 30 to 52 weeks of ethanol pretreatment. The results indicate a decrease of carbon tetrachloride toxicity with increased duration of ethanol pretreatment. This phenomenon could be attributed to reduced sensibility to those alcohol effects which are responsible for increase of carbon tetrachloride toxicity.
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PMID:Influence of ethanol pretreatment of differing duration on toxic effects of carbon tetrachloride in rats. 208 Sep 8


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