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:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The contribution of amino acid oxidation to total energy expenditure is negligible during short-term intense exercise and accounts for 3-6% of the total adenosine triphosphate supplied during prolonged exercise in humans. While not quantitatively important in terms of energy supply, the intermediary metabolism of several amino acids-notably glutamate, alanine, and the branched-chain amino acids-affects other metabolites, including the intermediates within the tricarboxylic acid (TCA) cycle. Glutamate appears to be a key substrate for the rapid increase in muscle TCA cycle intermediates (TCAI) that occurs at the onset of moderate to intense exercise, due to a rightward shift of the reaction catalyzed by alanine aminotransferase (glutamate + pyruvate <==> alanine + 2-oxoglutarate). The pool of muscle TCAI declines during prolonged exercise, and this has been attributed to an increase in leucine oxidation that relies on one of the TCAI. However, this mechanism does not appear to be quantitatively important due of the relatively low maximal activity of branched-chain oxoacid dehydrogenase, the key enzyme involved. It has been suggested that an increase in TCAI is necessary to attain high rates of aerobic energy production and that a decline in TCAI may be a causative factor in local muscle fatigue. These topics remain controversial, but recent evidence suggests that changes in TCAI during exercise are unrelated to oxidative energy provision in skeletal muscle.
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PMID:Regulation of skeletal muscle amino acid metabolism during exercise. 1125 39

Few data are available on enzyme activity in amphibian plasma or erythrocytes. We measured the activity of several blood enzymes in the urodele amphibian Pleurodeles waltl reared under standard laboratory conditions. In subsequent experiments, we will estimate and compare the physiological and biochemical conditions of P. waltl when reared under extreme temperature or microgravity conditions. The enzymes selected were glutamate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, superoxide dismutase, catalase, isocitrate dehydrogenase and glucose-6-phosphate dehydrogenase. In fresh plasma samples, enzyme activity in females was higher than in males, except for aspartate and alanine aminotransferases, which were equivalent in females and males. Glutamate dehydrogenase activity was higher in males than in females. In female erythrocytes, the activity of all enzymes was higher than in male erythrocytes. We have also studied the storage conditions of samples and observed that for most enzymes, the activity in freshly isolated plasma and erythrocyte preparations decreased after storage at -18 or +4 degrees C.
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PMID:Sex-linked differences in activity of enzymes in the blood of the urodele amphibian Pleurodeles waltl. 1169 17

The effect of antagonist pretreatment on the signaling properties of the human metabotropic glutamate 1a (hmGlu1a) receptor was examined in stably transfected L929sA cells. Pre-exposure of hmGlu1a receptor-expressing cells to the mGlu1 receptor antagonists (S)-4-carboxy-3-hydroxyphenylglycine and 7-(hydroxyimino)cyclo-propa[b]chromen-1a-carboxylate ethyl ester dramatically enhanced subsequent glutamate-induced phosphoinositide hydrolysis and intracellular [Ca(2+)] rise. We found clear indications that the antagonist-mediated enhancement of glutamate-evoked mGlu1a receptor signaling is caused by the development of mGlu1a receptor supersensitivity: the potency of glutamate was increased by 3-fold after 24 h antagonist pretreatment and the potency of the antagonists was significantly decreased in antagonist-pretreated cells. The kinetic profile of the antagonist-mediated enhancement showed that the maximal increase in intracellular [Ca(2+)] was already reached after 30-min pretreatment, suggesting that de novo receptor synthesis is not involved in the process of mGlu1a receptor supersensitization. Glutamate-mediated phosphoinositide hydrolysis increased up to 24 h after antagonist treatment. Although it seemed likely that the hmGlu1a receptor could desensitize after activation by endogenously present glutamate, removal of glutamate from the extracellular medium with GPT resulted in a much smaller enhancement of glutamate responsiveness. Moreover, the magnitude of antagonist-mediated receptor supersensitivity was much larger than the magnitude of agonist-induced receptor desensitization. These results suggest that antagonist-evoked mGlu1 receptor supersensitivity is not merely the result of a blockade of agonist-induced desensitization. Finally, we found that antagonist pretreatment doubled the amount of receptors at the cell surface. Our findings are the first lines of evidence that prolonged antagonist treatment can supersensitize the hmGlu1a receptor. In view of the potential therapeutic application of mGlu1 receptor antagonists, it will be important to know whether these phenomena occur in vivo.
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PMID:Supersensitivity of human metabotropic glutamate 1a receptor signaling in L929sA cells. 1196 Nov 43

Hepatotoxicity induced by 1,1-dichloroethylene (DCE) is mediated by cytochrome P450-dependent metabolism to reactive intermediates, including the epoxide. We have tested the hypothesis that mitochondria are a primary target of toxicity by investigating dose- and time-dependent effects of DCE on mitochondrial respiration. Hepatotoxicity, as assessed by serum alanine aminotransferase (ALT) activity, was evaluated. We have also determined the effectiveness of N-acetyl-L-cysteine (NAC) in protecting against respiratory perturbations and hepatotoxicity. Liver mitochondria were isolated 2 h after DCE (50, 75, 100, 125, and 150 mg/kg) treatment. Glutamate (complex I)- and succinate (complex II)-supported mitochondrial respiration was assessed by measurement of state 3 (ADP-stimulated) and state 4 (resting) rates of oxygen consumption. The corresponding respiratory control ratios (RCRs, state 3/state 4) and ADP:O ratios were then calculated. A DCE dose of 125 mg/kg significantly inhibited glutamate- and succinate-supported state 3 respiration, leading to a significant reduction in corresponding RCRs and ADP:O ratios. In time-dependent studies, state 3 respiration rates and RCRs for glutamate-supported respiration were significantly decreased as early as 20 min after DCE (125 mg/kg) treatment, whereas those for succinate-supported respiration were significantly decreased at 90 min. Additionally, ADP:O ratios for glutamate-supported respiration were significantly decreased starting at 60 min, and those for succinate-supported respiration at 90 min. Alterations in mitochondrial function preceded significant increases in ALT activity, which was first manifested at 2 h. Pretreatment with NAC (1200 mg/kg) abrogated DCE-induced GSH depletion and inhibited disturbances in mitochondrial respiration. Moreover, NAC protected against increased ALT activity, suggesting that the protective effect of NAC is due to increased GSH for conjugation reactions and/or its antioxidant property. These results showed that DCE-mediated mitochondrial dysfunction is an early event that preceded the onset of hepatotoxicity.
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PMID:Mitochondrial dysfunction is an early manifestation of 1,1-dichloroethylene-induced hepatotoxicity in mice. 1249 May 82

Physiological and biochemical perturbations in the liver of Carassius auratus were investigated in vivo following 40 days of exposure to ytterbium solutions of different concentration. Glutamate-pyruvate transaminase (GPT) activity in goldfish liver was stimulated at 0.05 mg/L Yb3+ and inhibited at higher Yb3+ concentrations. Activity of the antioxidant enzyme superoxide dismutase (SOD) was stimulated at Yb3+ higher than 0.05 mg/L, and catalase (CAT) activity was strongly inhibited after 40 days of exposure. Detoxifying enzymes glutathione S-transferase (GST) and glutathione peroxidase (GSH-Px) were stimulated at 0.05 mg/L and inhibited at 0.1 mg/L after 40 days of exposure. Among the parameters determined, CAT in goldfish liver was most sensitive to Yb3+, indicating that CAT might be considered a potential tool in the biomonitoring of exposure to Yb3+ in an aquatic ecosystem.
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PMID:Physiological responses of Carassius auratus to ytterbium exposure. 1256 69

Elimination of glutamate through enzymatic degradation is an alternative to glutamate receptor blockade in preventing excitotoxic neuronal injury. Glutamate pyruvate transaminase (GPT) is a highly active glutamate degrading enzyme that requires pyruvate as a co-substrate. This study examined the ability of GPT to protect neurons of the hippocampal slice preparation against glutamate toxicity. Two methods were used to elevate the concentration of glutamate in the peri-neuronal space. In an endogenous release paradigm, slices were incubated with 100-500 microM L-trans-pyrrolidine-2,4-dicarboxylate (PDC), an inhibitor of glutamate re-uptake. One hour of exposure to PDC in normal, pyruvate-free slice maintenance medium caused a dose dependent increase in neuronal death assessed 24 h later by propidium iodide uptake in dead cell nuclei. GPT (10 U/ml) decreased neuronal death caused by exposure to PDC at all PDC concentrations tested. Neuroprotection in this model was not dependent on added or non-physiologic levels of pyruvate. In a different paradigm, glutamate was added directly to the normal, pyruvate-free slice maintenance medium and not rinsed away, exposing the slices to a range of 1-5 mM glutamate for an extended period. Twenty-four hours later, neuronal death was again assessed by propidium iodide uptake. GPT was again neuroprotective, decreasing neuronal death in the range from 3 to 5 mM glutamate. In the setting of incubation with this large load of glutamate, neuroprotection by GPT was enhanced by adding pyruvate to the medium. GPT is an effective neuroprotectant against glutamate excitotoxicity. When exposure is limited to endogenously released glutamate, neuroprotection by GPT is not dependent on added pyruvate.
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PMID:Glutamate-pyruvate transaminase protects against glutamate toxicity in hippocampal slices. 1283 98

Glutamate is a major excitatory neurotransmitter in the mammalian brain. Nevertheless, high extracellular levels of this amino acid have been shown to be toxic to several neuronal populations, but no data are available to show how glutamate homeostasis is altered in response to local infusion of glutamate. In the present study, 1 microM of glutamate was stereotactically injected into cerebral cortex, striatum, and hippocampus of adult rat brain, and the activities of key metabolic enzymes, lactate dehydrogenase, glutamate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase were evaluated by postmortem analysis in tissue homogenates. The results show that glutamate bolus, induced significant alterations in vivo glutamate and energy metabolism, as evidenced by marked alterations in these enzyme activities, whereas dizocilpine, a glutamate receptor antagonist, negated many of the effects induced by high glutamate. However, the degree of involvement of these observations in glutamate-induced neurotoxicity remains to be ascertained.
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PMID:Metabolic responses in discrete regions of rat brain following acute administration of glutamate. 1293 56

Cephaloridine, which accumulates in the renal proximal tubule, is a model compound used for studying the toxicity of antibiotics towards this nephron segment. Several studies have demonstrated that cephaloridine alters renal intermediary and energy metabolism, but the mechanism by which this compound interferes with renal metabolic pathways remains incompletely understood. In an attempt to improve our knowledge in this field, we have studied the influence of cephaloridine on the synthesis of glutamine, which represents a key metabolic process involving several important enzymatic steps in the rabbit kidney. For this, suspensions of rabbit renal proximal tubules were incubated for 90 and 180 min in the presence of 5 mM alanine, an important glutamine precursor, both in the absence and the presence of 10 mM cephaloridine. Glutamate accumulation and glutamine synthesis were found to be inhibited by cephaloridine after 90 and 180 min of incubation, and cephaloridine accumulation in the renal proximal cells occurred in a time-dependent manner. The renal proximal tubule activities of alanine aminotransferase and glutamate dehydrogenase, which initiates alanine removal and releases the ammonia needed for glutamine synthesis, respectively, were inhibited to a significant degree and in a concentration-dependent manner by cephaloridine concentrations in the range found to accumulate in the renal proximal cells. Citrate synthase and glutamine synthetase activities were also inhibited by cephaloridine, but to a much lesser extent. The above enzymatic activities were not found to be inhibited when they were measured after successive dilutions of renal proximal tubules incubated for 180 min in the presence of 5 mM alanine and 10 mM cephaloridine. When microdissected segments (S1-S3) of rabbit renal proximal tubules were incubated for 180 min with 5 mM alanine with and without 5 and 10 mM cephaloridine, glutamate accumulation and glutamine synthesis were also inhibited in the three renal proximal segments studied; the latter cephaloridine-induced inhibitions observed were concentration-dependent except for glutamine in the S3 segment. These results are consistent with the view that cephaloridine accumulates and is toxic along the entire rabbit renal proximal tubule. They also demonstrate that cephaloridine interferes in a concentration-dependent and reversible manner mainly with alanine aminotransferase and glutamate dehydrogenase, which are therefore newly-identified targets of the toxic effects of cephaloridine in the rabbit renal proximal tubule.
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PMID:Identification of novel targets of cephaloridine in rabbit renal proximal tubules synthesizing glutamine from alanine. 1599 Oct 25

This study was designed to determine the toxic effects of nickel sulfate on the biochemical and elemental profile of liver in protein deficient rats. Nickel sulfate in the dose of 800mg/l in drinking water was administrated to Sprauge Dawley (S.D) normal control as well as protein deficient rats for a total duration of eight weeks. The effects of nickel treatment and protein deficiency when given separately and in combination were studied on rat liver marker enzymes like Alkaline phosphatase (ALP),Glutamate oxaloacetate transaminase (GOT), Glutamate pyruvate transaminase (GPT) and also on the status of essential elements in rat liver. Protein deficient, Ni treated as well as combined protein deficient and nickel treated rats showed significant reductions in the body weight and hepatic protein contents as compared to normal control rats. Hepatic alkaline phosphatase activity and alanine aminotransferase showed a significant elevation in rats subjected to protein deficiency, nickel treatment and combined protein deficiency and nickel treatment. As regards to hepatic levels of aspartate aminotransferase a significant elevation was observed in protein deficient and nickel treated protein deficient animals. Nickel administration to normal and protein deficient rats has resulted in a significant increase in concentrations of nickel, phosphorus and sulfur in liver tissue. The concentration of zinc and copper in liver tissue decreased significantly in protein deficient, nickel treated and nickel treated protein deficient animals. Tissue iron concentrations were found to be decreased in protein deficient animals, but the concentrations of iron got elevated significantly in nickel treated and nickel treated protein deficient animals. It has been observed that selenium got decreased significantly in protein deficient, nickel treated and nickel treated protein deficient animals when compared to normal animals. The elevation of selenium in nickel treated protein deficient animals was also significantly higher when compared to protein deficient animals.
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PMID:Ineffectiveness of nickel in augmenting the hepatotoxicity in protein deficient rats. 1633 21

Changes in the activity of a number of enzymes concerned with amino acid synthesis and metabolism were recorded for the endosperm, testa pericarp, and embryo of developing barley (Hordeum distichum L.) grains. Both glutamate-pyruvate transaminase and glutamate-oxaloacetate transaminase activities were present in all tissues and at all ages examined. Glutamate dehydrogenase activity was largely confined to endosperm while glutamine synthetase activity was mainly in the testa pericarp.Ammonium ion concentration was maximal in endosperm by 20 days after anthesis. Glutamate concentration varied in endosperm and was in the range of 3.5 to 8.5 mm between 20 and 45 days after anthesis. Significant levels of ammonium ion and glutamate were also present in the testa pericarp over the major part of the developmental period.
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PMID:Metabolism of Ammonium Ion and Glutamate in Relation to Nitrogen Supply and Utilization during Grain Development in Barley. 1666 Mar 38


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