Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.4.1.2 (glutamate dehydrogenase)
 4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Berenil (4,4-diamidinodiazoaminobenzene-diacetamide acetate) or Suramin [sodium salt of 8-(3-benzamido-4-methylbenzamido)-naphthalene-1,3,5-trisulfonic acid] treatment of rats infected with Trypanosoma b. brucei enhanced hepatic microsomal aniline hydroxylase and p-aminopyrine N-demethylase activities. While Suramin inhibited significantly the activities of cytoplasmic glutamate dehydrogenase and lactate dehydrogenase, Berenil had no effect. The kinetic profiles of these enzymes consistently showed a Km value similar to that of controls. Both cytosolic and microsomal glutathione-S transferase and microsomal epoxide hydratase were unaffected by Suramin. However, a significant increase in cytosolic glutathione-S transferase was observed with Berenil. Microsomal phospholipids were not affected by any of the drugs.
 ...
PMID:Response of the rat's hepatic drug-metabolizing enzyme system to chemotherapy of Trypanosoma b. brucei infections with Berenil and Suramin. 673 75

Acute, oral administration of 7.0 mg/kg calcium carbimide (calcium cyanamide) to rats, 2 h before sacrifice, produced complete inhibition of hepatic, low-Km (less than 1 microM acetaldehyde) mitochondrial and cytosolic aldehyde dehydrogenase enzymes and significantly inhibited high-Km (approximately 1 mM acetaldehyde) mitochondrial, cytosolic, and microsomal aldehyde dehydrogenase isozymes. Calcium carbimide had no effect on several other hepatic enzyme activities including mitochondrial glutamate dehydrogenase and monoamine oxidase, cytosolic alcohol dehydrogenase, microsomal NADPH-cytochrome c reductase, benzo[a]pyrene hydroxylase and aminopyrine N-demethylase activities, and microsomal cytochrome P-450 content. It is concluded that calcium carbimide is a more specific inhibitor of hepatic aldehyde dehydrogenase enzymes than disulfiram.
 ...
PMID:Specificity of hepatic aldehyde dehydrogenase inhibition by calcium carbimide (calcium cyanamide) in the rat. 686 Oct 4

This study was undertaken to evaluate the effects of chronic ethanol consumption on the hepatotoxicity of acetaminophen. Male Sprague-Dawley rats were pair fed a nutritionally adequate liquid diet containing either ethanol or isocaloric carbohydrate for 4-6 wk. Acetaminophen (0.5 g/kg body wt) was given intraperitoneally 12 h after ethanol withdrawal. By 36 h, frank hepatic centrilobular necrosis and a decrease in hepatic aminopyrine N-demethylase activity were observed in the ethanol-fed rats, whereas in controls the changes were minimal. Serum glutamyl oxaloacetic transaminase and glutamate dehydrogenase activities were significantly increased in ethanol-fed rats. Hepatic damage in ethanol fed rats was apparent already at 6 h, as evidenced by elevated serum enzyme activities and ultrastructural changes, particularly of the mitochondria. The depletion of hepatic glutathione content and the covalent binding of acetaminophen metabolite(s) were significantly greater in ethanol-fed rats than in controls. Urinary excretion of mercapturic acid conjugate during the first 12 h was also increased in ethanol-fed rats. In an in vitro study, covalent binding of acetaminophen metabolite(s) to microsomal protein was increased after ethanol feeding for 4-6 wk. Thus, chronic ethanol feeding increases the hepatotoxicity of acetaminophen; enhanced production of reactive metabolite(s) may be responsible.
 ...
PMID:Increased hepatotoxicity of acetaminophen after chronic ethanol consumption in the rat. 719 62

Reactions between ebselen and subcellular particles of rat liver were investigated by monitoring the activity of mitochondrial glutamate dehydrogenase and microsomal glucose 6-phosphate dehydrogenase. Rat small intestine lactate dehydrogenase was purified and was also used in the reaction between cytosolic protein and ebselen. Glutamate dehydrogenase in intact rat liver mitochondria was completely resistant to ebselen, but the enzyme was significantly inactivated in broken mitochondria mediated by Triton X-100, reflecting the fact that ebselen was not transported through the mitochondrial membrane into the matrix. Glucose 6-phosphate dehydrogenase in rat liver microsomes was inactivated by ebselen, accompanied by a slight decrease in the thiol groups of microsomal membrane protein. Purified cytosolic lactate dehydrogenase was inactivated concentration- and time-dependent by ebselen. The activity of rat small intestine lactate dehydrogenase abolished by ebselen was significantly restored by incubation with purified rat small intestine thioltransferase in the presence of reduced glutathione (GSH). The level of thiol groups in rat liver microsome membrane protein decreased by ebselen was partially restored by an incubation with purified rat liver thioltransferase in the presence of GSH. The results suggested that thioltransferase can cleave the Se-S conjugates between ebselen and cytosolic proteins or microsomal membrane proteins in the presence of GSH.
 ...
PMID:Modulation of subcellular particles of the rat small intestine and liver by ebselen. 765 15

Antipyrine clearance was used to assess microsomal oxidative function in eight female Churra breed sheep at 20, 30, 40, 60, 80 and 100 days after infection by an oral administration of 150 metacercariae of Fasciola hepatica. Experimental infection was ascertained by an ELISA test and by faecal analysis. A significant increase in plasma glutamate dehydrogenase (GLDH) activity from 20 days post-infection and in gamma-glutamyltransferase (GGT) activity from 40 days post-infection was found. Both enzyme activities reached maximum levels in plasma of infected sheep at 80 days post-infection, progressively decreasing thereafter. A significant reduction in the total plasma clearance of antipyrine occurred from 60 to 100 days post-infection and a significant increase in mean residence time occurred by 80 days post-infection. The decrease of antipyrine metabolism coincided with the entrance of parasites in bile ducts and the highest liver damage caused by migrating juvenile flukes.
 ...
PMID:Experimental ovine fasciolosis: antipyrine clearance as indicator of liver damage. 863 98

The main pathway for the hepatic oxidation of ethanol to acetaldehyde proceeds via ADH and is associated with the reduction of NAD to NADH; the latter produces a striking redox change with various associated metabolic disorders. NADH also inhibits xanthine dehydrogenase activity, resulting in a shift of purine oxidation to xanthine oxidase, thereby promoting the generation of oxygen-free radical species. NADH also supports microsomal oxidations, including that of ethanol, in part via transhydrogenation to NADPH. In addition to the classic alcohol dehydrogenase pathway, ethanol can also be reduced by an accessory but inducible microsomal ethanoloxidizing system. This induction is associated with proliferation of the endoplasmic reticulum, both in experimental animals and in humans, and is accompanied by increased oxidation of NADPH with resulting H2O2 generation. There is also a concomitant 4- to 10-fold induction of cytochrome P4502E1 (2E1) both in rats and in humans, with hepatic perivenular preponderance. This 2E1 induction contributes to the well-known lipid peroxidation associated with alcoholic liver injury, as demonstrated by increased rates of superoxide radical production and lipid peroxidation correlating with the amount of 2E1 in liver microsomal preparations and the inhibition of lipid peroxidation in liver microsomes by antibodies against 2E1 in control and ethanol-fed rats. Indeed, 2E1 is rather "leaky" and its operation results in a significant release of free radicals. In addition, induction of this microsomal system results in enhanced acetaldehyde production, which in turn impairs defense systems against oxidative stress. For instance, it decreases GSH by various mechanisms, including binding to cysteine or by provoking its leakage out of the mitochondria and of the cell. Hepatic GSH depletion after chronic alcohol consumption was shown both in experimental animals and in humans. Alcohol-induced increased GSH turnover was demonstrated indirectly by a rise in alpha-amino-n-butyric acid in rats and baboons and in volunteers given alcohol. The ultimate precursor of cysteine (one of the three amino acids of GSH) is methionine. Methionine, however, must be first activated to S-adenosylmethionine by an enzyme which is depressed by alcoholic liver disease. This block can be bypassed by SAMe administration which restores hepatic SAMe levels and attenuates parameters of ethanol-induced liver injury significantly such as the increase in circulating transaminases, mitochondrial lesions, and leakage of mitochondrial enzymes (e.g., glutamic dehydrogenase) into the bloodstream. SAMe also contributes to the methylation of phosphatidylethanolamine to phosphatidylcholine. The methyltransferase involved is strikingly depressed by alcohol consumption, but this can be corrected, and hepatic phosphatidylcholine levels restored, by the administration of a mixture of polyunsaturated phospholipids (polyenylphosphatidylcholine). In addition, PPC provided total protection against alcohol-induced septal fibrosis and cirrhosis in the baboon and it abolished an associated twofold rise in hepatic F2-isoprostanes, a product of lipid peroxidation. A similar effect was observed in rats given CCl4. Thus, PPC prevented CCl4- and alcohol-induced lipid peroxidation in rats and baboons, respectively, while it attenuated the associated liver injury. Similar studies are ongoing in humans.
 ...
PMID:Role of oxidative stress and antioxidant therapy in alcoholic and nonalcoholic liver diseases. 889 26

Whole body exposure of male rats to 7 Gy gamma irradiation increased lipid peroxidation in the liver resulting in biomembrane damage of subcellular structures and release of their enzymes. This is evidenced by increase of thiobarbituric acid-reactive substances (TBARS) in mitochondria, lysosomes and microsomes. This was associated with a decrease in activity of the enzymes specific for each subcellular fraction; namely, mitochondrial glutamate dehydrogenase (GDH), lysosomal beta-glucuronidase and microsomal glucose 6-phosphatase. This was paralleled by an increased activity of these enzymes in the cytosol. Rats were supplemented with lycopene, a carotenoid present in tomatoes (5 mg/kg weight/day), by gavage, for 7 days before exposure to 7 Gy gamma irradiation. This resulted in diminishing amount of TBARS recorded for each subcellular structure in the liver of irradiated animals. Significant amelioration in the decrease recorded for the activity of mitochondrial glutamate dehydrogenase, lysosomal beta-glucuronidase and microsomal glucose 6-phosphatase was observed. This was associated with significant amelioration in the increase recorded for the activity of these enzymes in the cytosol. It is postulated that lycopene could play an important role in the recovery of the integrity of biological membranes of the liver after radiation injury.
 ...
PMID:Role of lycopene in recovery of radiation induced injury to mammalian cellular organelles. 1126 92

A series of molecular species with approximately spherical shape and with molecular weights between 35,000 and 250,000 were shadowed with platinum while resting on a cleaved mica surface. They were backed, stripped from the surface, and examined by electron microscopy. Materials examined were: pepsin, liver alcohol dehydrogenase, yeast alcohol dehydrogenase, glutamic dehydrogenase, polyhedral virus protein (insect), fibrinogen substructure, alkaline phosphatase, and microsomal particles from Escherichia coli. Measurements were made of widths perpendicular to the shadowing direction and heights were deduced from shadow lengths. For those molecular species with well established molecular weights the average heights correlate very well with the diameter of the theoretical sphere but the average widths are too great by 50 to 80 A due to the lateral growth of the deposited metal. Although the distortion in shape of shadowed particles is relatively large, with standardized conditions for shadowing, it is possible to make allowance for the distortion and to obtain reasonably reliable estimates of the dimensions of spherical organic particles down to a molecular weight of about 35,000.
 ...
PMID:Measurement of globular protein molecules by electron microscopy. 1439 16

A detailed subfractionation of the non-pregnant porcine corpus luteum (CL) was performed employing differential centrifugation. Marker enzyme assays (i.e., lactate dehydrogenase for the cytosol, NADPH-cytochrome P450 reductase for the endoplasmatic reticulum, catalase (CAT) for peroxisomes, glutamate dehydrogenase for the mitochondrial matrix and acid phosphatase for lysosomes) in all subfractions obtained exhibited a pattern of distribution similar to that observed with rat liver. These subfractions should be useful in connection with many types of future studies. In disagreement with previous biochemical and morphological studies, peroxisomes (identified on the basis of catalase activity and by Western blotting of catalase and of the major peroxisomal membrane protein (PMP-70)) sedimented together with mitochondria (i.e., at 5000 x g(av) for 10 min) and not in the post-mitochondrial fraction prepared at 30,000 x g(av) for 20 min by Peterson and Stevensson. No other classical peroxisomal enzymes were detectable in the porcine ovary, raising questions concerning the function of peroxisomes in this organ. Furthermore, UDP-glucuronosyltransferase (UGT), generally considered to be an integral membrane protein anchored in the endoplasmatic reticulum, was recovered in both the cytosolic (i.e., the supernatant after centrifugation at 50,000 x g(av) for 1h) and the microsomal fraction of the porcine corpus luteum, even upon further centrifugation of the former. In contrast, UGT sediments exclusively in the microsomal fraction upon subfractionation of the liver and ovary from rat.
 ...
PMID:Detailed analytical subcellular fractionation of non-pregnant porcine corpus luteum reveals peroxisomes of normal size and significant UDP-glucuronosyltransferase activity in the high-speed supernatant. 1472 50


<< Previous 1 2 3