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:1.4.1.2 (glutamate dehydrogenase)
4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dopa decarboxylase (DDC) catalyzes the cleavage of alpha-methylDopa into 3,4-dihydroxyphenylacetone and ammonia, via the intermediate alpha-methyldopamine, which does not accumulate during catalysis. The ketone has been identified by high-performance liquid chromatography and mass spectroscopic analysis, and ammonia by means of glutamate dehydrogenase. Molecular oxygen is consumed during the reaction in a 1:2 molar ratio with respect to the products. The kcat and Km of this reaction were determined to be 5.68 min-1 and 45 microM, respectively. When the reaction is carried out under anaerobic conditions, alpha-methyldopamine is formed in a time-dependent manner and neither ammonia nor ketone is produced to a significant extent. The reaction is accompanied by a time- and concentration-dependent inactivation of the enzyme with kinact of 0. 012 min-1 and Ki of 39.3 microM. Free 3,4-dihydroxyphenylacetone binds to the active site of DDC and inactivates the enzyme in a time- and concentration-dependent manner with a kinact/Ki value similar to that of alpha-methylDopa. d-Dopa, a competitive inhibitor of DDC, protects the enzyme against inactivation. Taken together, these findings indicate the active site directed nature of the interaction of DDC with 3,4-dihydroxyphenylacetone and provide evidence that the ketone generated by the reaction of DDC with alpha-methylDopa dissociates from the active site before it inactivates the enzyme. Inactivation of the enzyme by ketone followed by NaB3H4 reduction and chymotryptic digestion revealed that the lysine residue which binds pyridoxal 5'-phosphate (PLP) in the native enzyme is the site of covalent modification. Together with the characterization of the adduct released from the inactivated DDC, these data suggest that the enzyme is inactivated by trapping the coenzyme in a ternary adduct with ketone and the active site lysine. As recently reported for serotonin (5-HT) [Bertoldi, M., Moore, P. S., Maras, B., Dominici, P., and Borri Voltattorni, C. (1996) J. Biol. Chem. 271, 23954-23959], the conversion of dopamine (DA) into 3,4-dihydroxyphenylacetaldehyde and ammonia catalyzed by DDC is accompanied by irreversible loss of decarboxylase activity. However, the comparison between the absorbance, fluorescence, and CD features of DDC after 5-HT- or 3, 4-dihydroxyphenylacetone-induced inactivation shows that a different covalent adduct is formed between either of these two molecules and DDC-bound PLP.
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PMID:Reaction of dopa decarboxylase with alpha-methyldopa leads to an oxidative deamination producing 3,4-dihydroxyphenylacetone, an active site directed affinity label. 957 73

The quality of cold-stored donor livers slowly declines beyond approximately 12 h, although these organs may still be used for clinical transplantation. The aim of the present study was to improve the energetic status and viability of long-term-preserved livers by short-term gaseous oxygen insufflation prior to implantation of the organ using a technique that has already been shown to promote aerobic energy metabolism during hypothermia. Livers from ten male Wistar rats were isolated, rinsed blood-free. Five livers (group 1) were stored for 48 h at 4 degrees C in UW preservation solution, and five livers (group 2) were isolated and stored in the same manner for 47 h, and were then, during the last 60 min of the preservation period, connected to a persufflation device and gaseous oxygen was introduced into the organ via the inferior caval vein, with the liver still immersed in cold UW solution. This technique of endischemic gaseous oxygenation resulted in a significant normalization of vascular resistance upon isolated reperfusion in vitro and a reduction in hepatic efflux of alanine aminotransferase as well as glutamate dehydrogenase, which led to improved recovery of the reperfused grafts of group 2 as evidenced by an elevated energy charge potential at the end of the reperfusion period. In conclusion, the technique described seemed effective in enhancing the preoperative viability of marginal donor grafts.
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PMID:Endischemic oxygen persufflation to improve viability of marginally preserved donor livers. 966 26

Livers of fasted rats were perfused over 120 min in a recirculating hemoglobin-free system. Hepatotoxic injury induced by the addition of 1-butanol (130.2 mmol/l), CdCl2 (0.1 mmol/l), CuCl2 (0.03 mmol/l), Na3VO4 (2 mmol/l) or t-butylhydroperoxide (t-BuOOH, 0.5 mmol/l) to the perfusate was shown by strong increases in lactate dehydrogenase (LDH) and glutamate-pyruvate transaminase (GPT) release, decreased oxygen consumption between 50 and 60%, and a nearly complete suppression of bile flow. Hepatic adenosine triphosphate (ATP) and reduced glutathione (GSH) concentrations were reduced by between 30 and 80%, and 20 and 80% respectively. Only Na3VO4 and t-BuOOH evoked increased releases of glutamate dehydrogenase (GLDH) in the perfusate. Malondialdehyde (MDA) concentrations were enhanced by all toxicants in the perfusate and by all except 1-butanol in the liver. The MDA increase, however, was much higher after Na3VO4 and t-BuOOH than after the other toxicants. When glycine (12 mmol/l) was added 30 min before the toxicants to the perfusate it prevented the enzyme releases induced by all hepatotoxic agents by about 80%. Furthermore, glycine prevented the Na3VO4 induced increase of MDA in liver and perfusate, the hepatic ATP and GSH level reductions induced by 1-butanol and attenuated the reduction of oxygen consumption induced by CuCl2 and t-BuOOH. Glycine, however, did not reverse the reductions of oxygen consumption induced by CdCl2 and Na3VO4, the suppressions of bile flow and, with the exception of 1-butanol, the decreases of hepatic ATP levels induced by all agents.
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PMID:Influence of glycine on the damage induced in isolated perfused rat liver by five hepatotoxic agents. 970 6

The role of endogenous and internalized catalase in the protection of Plasmodium against oxidant stress was studied. Catalase activities were measured in isolated Plasmodium falciparum at different stages of intererythrocytic development. Activities measured at late schizont stages were compared to parasite markers (glutamate dehydrogenase, SOD) and to red blood cell markers (haemoglobin, Cu/Zn-SOD). The fate of the host cell catalase in the parasite digestive system was studied by immunoelectron microscopy using monoclonal antibodies. The internalized catalase appeared to be dissociated in the digestive system of the parasite and inactivated. To examine the protective role of the endogenous and internalized catalase in the parasite protection against oxidant stress, parasites were cultivated at two oxygen concentrations (5% and 20%) in inhibited catalase red blood cells. These experiments suggested that the catalases present both in red blood cell and parasite are not essential when parasites are cultivated under 5% oxygen, but are necessary to protect the parasite under 20% oxygen. Catalase may not be the main protective enzyme involved in the protection of P. falciparum in standard in vitro culture conditions, but may become critical under the higher oxygen tensions conditions encountered in vivo.
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PMID:Status of Plasmodium falciparum towards catalase. 979 89

The interaction between glycolysis, glutaminolysis and tumor growth in WAG/Fra rnu/rnu rats has been investigated. Small tumors are characterized by a low conversion of glucose to lactate whereas the conversion of glutamine to lactate is high. In medium sized tumors the flow of glucose to lactate as well as oxygen utilization are increased whereas glutamine and serine consumption are reduced. At this stage the tumor cells start with glutamate and alanine production. Large tumors are characterized by a low oxygen and glucose supply but a high glucose and oxygen utilization rate. The conversion of glucose to glycine, alanine, glutamate, glutamine, and proline reaches high values and the amino acids are released. Pyruvate kinase increases with tumor weight and is positively correlated with an increase in glucose and oxygen utilization. The shift from glutamate consumption to glutamate production is correlated with an increase in glutamate dehydrogenase and glutamate oxaloacetate transaminase activity.
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PMID:Pyruvate kinase and the interaction of amino acid and carbohydrate metabolism in solid tumors. 985 94

We investigated the acute toxic and metabolic effects of 23-aliphatic alcohols (16 saturated and 7 unsaturated) in the isolated perfused rat liver at a concentration of 65.1 mmol/l (approximately 0.3% ethanol). The capacity of the straight chain primary alcohols (methanol, ethanol, 1-propanol, 1-butanol and 1-pentanol) to release the enzymes glutamate-pyruvate transaminase (GPT), lactate dehydrogenase (LDH) and glutamate dehydrogenase (GLDH) into the perfusate was strongly correlated with their carbon chain length. The secondary alcohols were less active in this respect whereas branching of the carbon chain did not consistently change alcohol toxicity. Unsaturation in the straight chain but not in the branched chain alcohols was accompanied by an increase in toxicity. An increased enzyme release was in general accompanied by, and correlated to, reductions in oxygen consumption, bile secretion, and perfusion flow of the isolated livers. Statistically significant correlations exist between parameters of alcohol-induced hepatotoxicity and the membrane/buffer partition coefficents of the alcohols. With the exception of methanol, all alcohols tested increased the lactate/pyruvate ratio of the perfusate, although this effect was not correlated to the degree of hepatic injury. Hepatic ATP concentrations decreased in most cases in line with hepatic injury and were particularly correlated with changes in oxygen consumption. Hepatic concentrations of reduced glutathione (GSH) were only diminished by the unsaturated alcohols, whereas an increase in hepatic oxidized glutathione (GSSG) occurred only with some of the saturated alcohols. Hepatic concentrations of malondialdehyde (MDA) increased after two saturated and three unsaturated alcohols but did not correlate with other parameters of hepatotoxicity. In conclusion, alcohol-induced hepatotoxicity is primarily due to membrane damage induced by the direct solvent properties of the alcohols. The consequences and relative contributions of alcohol metabolization to the overall hepatotoxicity of higher alcohols requires further study.
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PMID:The toxic and metabolic effects of 23 aliphatic alcohols in the isolated perfused rat liver. 1036 51

Lung transplant (LTx) recipients have a low peak work rate, peak oxygen consumption (V O2peak), and early lactate threshold on incremental exercise. We hypothesized that LTx recipients have reduced oxidative function and altered fiber type proportion in peripheral skeletal muscle. Seven stable LTx recipients and seven age- and sex-matched control subjects were studied. Incremental exercise testing with arterialized venous sampling and a resting quadriceps femoris punch muscle biopsy were performed. Muscle specimens were analyzed for fiber type proportion, metabolites, oxidative and glycolytic enzyme activities, and mitochondrial ATP production rate (MAPR) using standard techniques. The results showed that mean V O2peak in LTx recipients was 52% of control subjects. Compared with the control subjects, LTx skeletal muscle exhibited: (1) a lower MAPR; (2) lower activity of the mitochondrial enzymes glutamate dehydrogenase (GDH), citrate synthase (CS), 2-oxogluterate dehydrogenase (OGDH), and 3-hydroxyacyl-CoA-dehydrogenase (HAD). There was no difference in the activities of anaerobic enzymes, except for higher phosphofructokinase activity; (3) a lower proportion of type I fibers; (4) a higher lactate and inosine monophosphate (IMP) content and a lower ATP content at rest indicating a high reliance on anaerobic metabolism. The reduced type I fiber proportion and severely reduced mitochondrial oxidative capacity may play an important role in exercise limitation after LTx.
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PMID:Skeletal muscle oxidative capacity, fiber type, and metabolites after lung transplantation. 1039 Mar 80

The effect of various metabolic inhibitors on the rate of oxygen consumption by procyclic culture forms of Trypanosoma congolense utilizing proline as substrate was investigated. Cyanide inhibited the rate of oxygen consumption by 81.0 +/- 6.7%, malonate inhibited the rate by 51.6 +/- 1.6% and Antimycin A by 73.1 +/- 5.9%. A combination of cyanide and malonate inhibited the rate of oxygen consumption by 84.9 +/- 6.7% while a combination of antimycin A and malonate inhibited the rate by 81.6 +/- 7.6%. Rotenone had no effect on the rate of respiration except when the intact cells were first permeabilized by digitonin after which rotenone decreased the rate of respiration by 20-30%. Salicylhydroxamate (SHAM) did not have any effect on the rate of oxygen consumption. Enzymes involved in the catabolism of proline with high activities were: proline dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, fumarase, NADP-linked malic enzyme, alanine aminotransferase and malate dehydrogenase. Activities of 1-pyrroline-5 carboxylate dehydrogenase, glutamate dehydrogenase, aspartate aminotransferase and NAD-linked malic enzyme were detectable but lower. The end products of proline catabolism were alanine and glutamate. Unlike the case in Trypanosoma brucei brucei aspartate was not detected. Possible pathways of proline catabolism in procyclic culture forms of T. congolense and of electron transfer are proposed.
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PMID:Catabolism of proline by procyclic culture forms of Trypanosoma congolense. 1042 13

Ornithine decarboxylase (ODC) from Lactobacillus 30a catalyses the cleavage of alpha-methylornithine into ammonia and 2-methyl-1-pyrroline; glutamate decarboxylase (GAD) from Escherichia coli catalyses the cleavage of alpha-methylglutamate into ammonia and laevulinic acid. In our analyses, 2-methyl-1-pyrroline and laevulinic acid were identified by HPLC and mass spectroscopic analysis, and ammonia was identified by means of glutamate dehydrogenase. Molecular oxygen was consumed during these reactions in a 1:2 molar ratio with respect to the products. The catalytic efficiencies (k(cat)/K(m)) of the reactions catalysed by ODC and GAD were determined as 12500 and 9163 M(-1).min(-1) respectively. When the reactions were performed under anaerobic conditions, no ammonia, 2-methyl-1-pyrroline or laevulinic acid was produced to a significant extent. The formation of ammonia and O(2) consumption (in a 1:2 molar ratio with respect to ammonia) were also detected during the reaction of ODC and GAD with putrescine and gamma-aminobutyrate respectively. Taken together, these findings clearly indicate that ODC and GAD catalyse an oxidative deamination of their decarboxylation products, a reaction similar to that catalysed by dopa decarboxylase (DDC) with alpha-methyldopa [Bertoldi, Dominici, Moore, Maras and Borri Voltattorni (1998) Biochemistry 37, 6552-6561]. Furthermore, this reaction was accompanied by a decarboxylation-dependent transamination occurring for GAD, DDC and ODC with a frequency of approx. 0.24%, 1% and 9% respectively compared with that of oxidative deamination.
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PMID:Ornithine and glutamate decarboxylases catalyse an oxidative deamination of their alpha-methyl substrates. 1047 60

The liver is the major site of gluconeogenesis, the major organ of amino acid catabolism and the only organ with a complete urea cycle. These metabolic capabilities are related, and these relationships are best exemplified by an examination of the disposal of the daily protein load. Adults, ingesting a typical Western diet, will consume approximately 100 g protein/d; the great bulk of this is metabolized by the liver. Although textbooks suggest that these amino acids are oxidized in the liver, total oxidation cannot occur within the confines of hepatic oxygen uptake and ATP homeostasis. Rather, most amino acids are oxidized only partially in the liver, with the bulk of their carbon skeleton being converted to glucose. The nitrogen is converted to urea and, to a lesser extent, to glutamine. The integration of the urea cycle with gluconeogenesis ensures that the bulk of the reducing power (NADH) required in the cytosol for gluconeogenesis can be provided by ancillary reactions of the urea cycle. Glutamate is at the center of these metabolic events for three reasons. First, through the well-described transdeamination system involving aminotransferases and glutamate dehydrogenase, glutamate plays a key catalytic role in the removal of alpha-amino nitrogen from amino acids. Second, the "glutamate family" of amino acids (arginine, ornithine, proline, histidine and glutamine) require the conversion of these amino acids to glutamate for their metabolic disposal. Third, glutamate serves as substrate for the synthesis of N-acetylglutamate, an essential allosteric activator of carbamyl phosphate synthetase I, a key regulatory enzyme in the urea cycle.
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PMID:Glutamate, at the interface between amino acid and carbohydrate metabolism. 1073 67


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