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

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.
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PMID:Specificity of hepatic aldehyde dehydrogenase inhibition by calcium carbimide (calcium cyanamide) in the rat. 686 Oct 4

Two sensitive assays, one which fluorometrically measures only the L isomer of 2-keto-4-hydroxyglutarate after decarboxylation to L-malate and the other which spectrophotometrically determines both enantiomers by reductive amination with glutamate dehydrogenase, are described. By use of these assays, the steady-state kinetics of the aldol condensation of pyruvate with glyoxylate, as catalyzed by 2-keto-4-hydroxyglutarate aldolase from either bovine liver or Escherichia coli, were studied as was the inhibition of this reaction by glyoxylate and other anions. For the E. coli aldolase, double-reciprocal plots are linear except at high (above 5 mM) glyoxylate concentrations; apparent Km values increase with increasing concentrations of the fixed substrate. The data are consistent with an ordered reaction sequence. Inhibition by halides follows the lyotropic or Hofmeister series. Esters are not good inhibitors; mono-, di-, and tricarboxylic acids are increasingly inhibitory. Of the substrate analogues tested, hydroxypyruvate is the most potent inhibitor. Inhibition studies with citrate, acetaldehyde, and glyoxylate (all competitive inhibitors) suggest there are two domains at the active site-the Schiff base forming lysyl residue which interacts with carbonyl analogues (like acetaldehyde) and a center of positive charge which binds anions (like citrate). In contrast to the bacterial enzyme, liver 2-keto-4-hydroxyglutarate aldolase is inhibited in a competitive manner by much lower concentrations (0.1 mM or even lower) of glyoxylate. Many salts and some carboxylic acids activate the liver enzyme. Similarly, substrate analogues like 2-ketobutyrate and fluoropyruvate are mild activators; no effect is seen with acetaldehyde. Besides glyoxylate, only glyoxal, 2-ketoglutarate, and hydroxypyruvate inhibit the aldol condensation reaction. A uniform value of 1 is found for the number of inhibitor molecules bound per active site of either liver or E. coli 2-keto-4-hydroxyglutarate aldolase.
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PMID:Steady-state kinetics and inhibition studies of the aldol condensation reaction catalyzed by bovine liver and Escherichia coli 2-keto-4-hydroxyglutarate aldolase. 701 77

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.
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PMID:Role of oxidative stress and antioxidant therapy in alcoholic and nonalcoholic liver diseases. 889 26

1. The activities of the enzymes of the citric acid cycle, the glyoxylate by-pass and some other enzymes acting on the substrates of these cycles have been measured at the pH of the yeast cell during the aerobic growth of yeast on different carbon sources and in different growth media. 2. Sugars induced an anaerobic type of metabolism as measured by ethanol production. Glucose was much more effective in inducing the anaerobic pathways than was galactose. The production of ethanol by cells grown on pyruvate was very small. 3. Glucose was also a more effective repressor than was galactose of the citric acid-cycle enzymes but both were equally effective in repressing almost completely the enzymes of the glyoxylate by-pass. 4. Disappearance of the sugars from the growth medium resulted in an increase in the activities of the enzymes of the citric acid cycle and in the appearance of substantial activities of the enzymes of the glyoxylate cycle. By contrast, the activities of purely biosynthetic enzymes (glutamate-oxaloacetate transaminase, NADP(+)-linked glutamate dehydrogenase) and of pyruvate decarboxylase were decreased. 5. The 2-oxoglutarate-oxidase system was found to be the least active enzyme of the citric acid cycle. 6. The regulatory control at the levels of pyruvate and acetaldehyde and the control of the citric acid cycle are discussed.
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PMID:Changes in the enzyme activities of Saccharomyces cerevisiae during aerobic growth on different carbon sources. 1674 16

Concentrations of acetaldehyde, ethanol, ethyl acetate (EA), organic acids and activities and gene expression of alcohol dehydrogenase (ADH; EC 1.1.1.1), pyruvate decarboxylase (PDC; EC 4.1.1.1), alcohol acyltransferase (AAT; EC 1.4.1.14), malate dehydrogenase (MDH; EC 1.1.1.37), malic enzyme (ME; EC 1.1.1.40) and glutamate dehydrogenase (EC 1.4.1.14) were investigated in two strawberry (Fragaria x ananassa Duch) cultivars with different responses to CO(2) during storage. 'Jewel' fruit treated with CO(2) accumulated acetaldehyde and ethanol but little EA, while 'Cavendish' accumulated little acetaldehyde or ethanol but accumulated EA. In CO(2)-treated fruit, PDC activity was positively correlated with EA accumulation in 'Jewel' but not in 'Cavendish', while no differential effect of atmosphere was observed on its gene expression. ADH activity and gene expression show a correlation with ethanol accumulation in 'Cavendish'. In 'Jewel', there was a positive correlation between ADH gene expression and enzyme activity; however, this correlation does not explain ethanol accumulation in this cultivar. EA accumulation did not show any correlation with AAT activity and gene expression in any of the cultivars. Succinate concentrations were highest and those of malate lowest in CO(2)-treated fruit of both cultivars, but MDH and ME activities were not affected by CO(2). Gene expression of MDH and ME were not affected by atmosphere in 'Cavendish', although in 'Jewel' the MDH expression was slightly lower in CO(2)- than air-treated fruit. The results of this study show that differences in fermentation products and malate accumulation in CO(2)-treated strawberry fruit are not consistently correlated with enzyme activities and gene expression.
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PMID:Fermentation and malate metabolism in response to elevated CO2 concentrations in two strawberry cultivars. 1849 36

The effect of univalent cations on activity of key enzymes of C2-metabolism has been investigated in the producer of biosurfactants, Acinetibacter calcoaceticus IMV B-7241 grown on ethanol. It was established that potassium cations are inhibitors of pyroquinolinequinone-dependent alcohol- and acetaldehyde dehydrogenases, the enzymes of biosynthesis of surface-active aminolipids (NADP-dependent glutamate dehydrogenase) and glycolipids (phosphoenopyruvate (PhEP)-carboxikinase), while ammonium cations are activators of these enzymes and PhEP-carboxylase. A decrease of potassium cations concentration in the cultivation medium to 1 mM and increase of the content of amine nitrogen to 10 mM as a result of potassium nitrate substitution by equimolar, as to nitrogen, urea concentration were accompanied by the increase of activity of enzymes of ethanol metabolism and SAS biosynthesis, as well as by the 2-fold increase of conditional concentration of the biosurfactants.
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PMID:[Effect of univalent cations on synthesis of surfactants by Acinetobacter calcoaceticus IMV B-7241]. 2372 Sep 59


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