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)

During the course of testing chronic toxicity in rats several physiological and biochemical parameters were investigated. Many of the processes studied show a circadian and infradian rhythm, which can clearly be influenced from the second year onwards by age dependent alterations. The daily rhythm of the following processes were investigated: Hexobarbital sleeping time, aminophenazone demethylation, Hb (Hemoglobin), Hc (Hematocrit), GPT (Glutamate-pyruvate-transaminase) and total plasma proteins. The seasonal changes of total plasma proteins, Hexobarbital sleeping time and aniline hydroxylation were also examined. The results obtained indicate, that for comparison and interpretation of data on acute and chronic toxicity the knowledge of daily and seasonal changes is necessary and has to be considered for an exact planning of experiments.
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PMID:Planning of experiments for the testing of chronic toxicity in rats taking into account biorhythms. 693 52

Measurements have been made of the hepatic soluble and mitochondrial GOT and GPT and mitochondrial NAD+ glutamate dehydrogenase activities in thioacetamide-treated rats for 30 days. There is a significant fall in the GOT and GPT soluble activities from the effect of chronic thioacetamide administration while the mitochondrial activities become markedly increased in both cases. Glutamate dehydrogenase also increased from the effect of this hepatotoxic substance. Protein determined in the soluble and mitochondrial fractions, showed decreased levels in the cytosolic extracts and increased levels in the mitochondrial ones. Morphological aspects of liver cells showed hypertrophic mitochondria located around the likewise hypertrophic nucleus. The existence of functionally very active mitochondria in the generating liver, induced by thioacetamide, as well as metabolic mechanisms for the regulating control under pathological circumstances, can be a consequence of the increased ammonia concentration.
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PMID:[Changes caused by thioacetamide in GOT and GPT aminotransferases and glutamate dehydrogenase in rat liver. Ultrastructural study]. 714 64

1. The metabolism of L-alanine was studied in isolated guinea-pig kidney-cortex tubules. 2. In contrast with previous conclusions of Krebs [(1935) Biochem. J. 29, 1951-1969], glutamine was found to be the main carbon and nitrogenous product of the metabolism of alanine (at 1 and 5 mM). Glutamate and ammonia were only minor products. 3. At neither concentration of alanine was there accumulation of glucose, glycogen, pyruvate, lactate, aspartate or tricarboxylic acid-cycle intermediates. 4. Carbon-balance calculations and the release of 14CO2 from [U-14C]alanine indicate that oxidation of the alanine carbon skeleton occurred at both substrate concentrations. 5. A pathway involving alanine aminotransferase, glutamate dehydrogenase, glutamine synthetase, pyruvate dehydrogenase, pyruvate carboxylase and enzymes of the tricarboxylic acid cycle is proposed for the conversion of alanine into glutamine. 6. Strong evidence for this pathway was obtained by: (i) suppressing alanine removal by amino-oxyacetate, and inhibitor of transaminases, (ii) measuring the release of 14CO2 from [1-14C]alanine, (iii) the use of L-methionine DL-sulphoximine, an inhibitor of glutamine synthetase, which induced a large increase in ammonia release from alanine, and (iv) the use of fluoroacetate, an inhibitor of aconitase, which inhibited glutamine synthesis with concomitant accumulation of citrate from alanine. 7. In this pathway, the central role of pyruvate carboxylase, which explains the discrepancy between our results and those of Krebs (1935), was also demonstrated.
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PMID:The conversion of alanine into glutamine in guinea-pig renal cortex. Essential role of pyruvate carboxylase. 733 38

Glutamate pyruvate transaminase (GPT) has been studied in the red cells of 46 patients with a confirmed diagnosis of polycythaemia rubra vera (PRV). The red cells of many of the patients showed low levels of enzyme activity. This activity could be restored by in vitro incubation with pyridoxal phosphate suggesting that the effect was due to low levels of B6 rather than to a primary abnormality of the GPT. Patients with the lowest levels of GPT activity were likely to have clonal chromosomal abnormalities in the bone marrow cells, particularly 20q-. Among 43 patients in whom the GPT phenotypes could be determined by an electrophoretic method there was a marked deficiency of heterozygotes. This disturbance in phenotypic expression may be related to the clonal nature of the disease in PRV, the clone showing lack of response to homeostatic controls and irregularities of gene expression.
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PMID:Glutamic pyruvate transaminase phenotypes in polycythaemia rubra vera. 737 7

The C57BL/10 SPS/sps mouse mutant are audiogenic seizure-susceptible. The enzymatic activities of glutamate decarboxylase (GAD), GABA aminotransferase (GABA-T), alanine aminotransferase (ALA-T), aspartate aminotransferase (ASP-T), and glutamate dehydrogenase (GDH) of whole brain supernatant are significantly reduced in these epileptic mice. GABA uptake is decreased in cortex, midbrain, and pons medulla. Previous studies showed the presence of two sodium-dependent GLU uptake systems in normal (SPS/SP) mice. Glutamate Umax by System 1 is significantly decreased in these mice, whereas the Umax value for System 2 is significantly increased in the epileptic mice.
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PMID:Altered GABAergic and glutamatergic transmission in audiogenic seizure-susceptible mice. 788 3

Morphological changes in mitochondria are observed early in the course of acetaminophen (AA)-induced hepatotoxicity, and mitochondrial dysfunction has been observed both in vivo and in vitro following exposure to AA. This study examined the early effects of AA exposure in vivo on mitochondrial respiration and evaluated the effectiveness of N-acetyl-L-cysteine (NAC) in protecting against respiratory dysfunction. Mitochondria were isolated from the livers of fasted, male CD-1 mice 0, 0.5, 1, 1.5 or 2 h after administration of a hepatotoxic dose of AA (750 mg/kg). Glutamate- and succinate-supported mitochondrial respiration were subsequently assessed by polarographic measurement of state 3 (ADP-stimulated) and state 4 (resting) rates of oxygen consumption and determination of the corresponding respiratory control ratios (RCR: state 3/state 4) and ADP:O ratios. Hepatotoxicity was assessed histologically and by measuring plasma alanine aminotransferase (ALT) activity. The earliest sign of mitochondrial dysfunction observed in this study was a significant decrease in the ADP:O ratio for the oxidation of glutamate 1 h post-dosing. At 1.5 and 2 h post-dosing the RCRs for both glutamate- and succinate-supported respiration were significantly decreased. All of the respiratory parameters measured in this study were significantly decreased, with the exception of succinate-supported state 4 respiration which was significantly increased, 2 h after AA administration. Thus, inhibition of mitochondrial respiration preceded overt hepatic necrosis, indicated by an elevation of ALT activity, which was not observed until 3 and 4 h post-dosing. In addition, mitochondrial respiratory dysfunction correlated with morphological alterations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of mitochondrial respiration in vivo is an early event in acetaminophen-induced hepatotoxicity. 817 80

The rabbit kidney does not readily metabolize but synthesizes glutamine at high rates by pathways that remain poorly defined. Therefore, the metabolism of variously labeled [13C]- and [14C]glutamates has been studied in isolated rabbit kidney tubules with and without acetate. CO2, glutamine, and alanine were the main carbon and nitrogenous end products of glutamate metabolism but no ammonia accumulated. Absolute fluxes through enzymes involved in glutamate metabolism, including enzymes of four different cycles operating simultaneously, were assessed by combining mainly the 13C NMR data with a new model of glutamate metabolism. In contrast to a previous conclusion of Klahr et al. (Klahr, S., Schoolwerth, A. C., and Bourgoignie, J. J. (1972) Am. J. Physiol. 222, 813-820), glutamate metabolism was found to be initiated by glutamate dehydrogenase at high rates. Glutamate dehydrogenase also operated at high rates in the reverse direction; this, together with the operation of the glutamine synthetase reaction, masked the release of ammonia. Addition of acetate stimulated the operation of the "glutamate --> alpha-ketoglutarate --> glutamate" cycle and the accumulation of glucose but reduced both the net oxidative deamination of glutamate and glutamine synthesis. Acetate considerably increased flux through alpha-ketoglutarate dehydrogenase and citrate synthase at the expense of flux through phosphoenolpyruvate carboxykinase; acetate also caused a large decrease in flux through alanine aminotransferase, pyruvate dehydrogenase, and the "substrate cycle" involving oxaloacetate, phosphoenolpyruvate, and pyruvate.
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PMID:The rabbit kidney tubule simultaneously degrades and synthesizes glutamate. A 13C NMR study. 903 May 22

The anaerobic fungus Piromyces sp. strain E2 appeared restricted in nitrogen utilization. Growth was only supported by ammonium as source of nitrogen. Glutamine also resulted in growth, but this was due to release of ammonia rather than to uptake and utilization of the amino acid. The fungus was not able to grow on other amino acids, albumin, urea, allantoin, or nitrate. Assimilation of ammonium is very likely to be mediated by NADP-linked glutamate dehydrogenase (NADP-GDH) and glutamine synthetase (GS). One transaminating activity, glutamate-oxaloacetate transaminase (GOT), was demonstrated. Glutamate synthase (GOGAT), NAD-dependent glutamate dehydrogenase (NAD-GDH), and the transaminating activity glutamate-pyruvate transaminase (GPT) were not detected in cell-free extracts of Piromyces sp. strain E2. Specific enzyme activities of both NADP-GDH and GS increased four- to sixfold under nitrogen-limiting conditions.
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PMID:The anaerobic fungus Piromyces sp. strain E2: nitrogen requirement and enzymes involved in primary nitrogen metabolism. 908 17

The role of glutamate transporters in the regulation of synaptic depression was examined in the avian nucleus magnocellularis. Repetitive stimulation of presynaptic auditory nerve fibers resulted in acute depression of EPSCs. Pharmacological blockade of glutamate transport in glial cells enhanced residual glutamate in the synaptic cleft and markedly increased the extent of depression at stimulus frequencies above 20 Hz via a postsynaptic mechanism. Glutamate pyruvate transaminase, a glutamate scavenger, accelerated the decay of the EPSC and reduced synaptic depression, indicating that transporters are not completely effective in rapid removal of glutamate. Regulation of residual transmitter by glia may thus serve to control synaptic strength in a frequency-dependent manner.
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PMID:Control of synaptic depression by glutamate transporters. 1068 6

Axenic mycelia of the ectomycorrhizal basidiomycete, Suillus bovinus, were grown in liquid media under continuous aeration with compressed air at 25 degrees C in darkness. Provided with glucose as the only carbohydrate source, they produced similar amounts of dry weight with ammonia, with nitrate or with alanine, 60-80% more with glutamate or glutamine, but about 35% less with urea as the respectively only exogenous nitrogen source. In crude extracts of cells from NH4(+)-cultures, NADH-dependent glutamate dehydrogenase exhibited high aminating (688 nmol x mg protein(-1) x min(-1)) and low deaminating (21 nmol x mg protein(-1) x min(-1)) activities. Its Km-values for 2-oxoglutarate and for glutamate were 1.43 mM and 23.99 mM, respectively. pH-optimum for amination was about 7.2, that for deamination about 9.3. Glutamine synthetase activity was comparatively low (59 nmol x mg protein(-1) x min(-1)). Its affinity for glutamate was poor (Km = 23.7 mM), while that for the NH4+ replacing NH2OH was high (Km = 0.19 mM). pH-optimum was found at 7.0. Glutamate synthase (= GOGAT) revealed similar low activity (62 nmol x mg protein(-1) x min(-1)), Km-values for glutamine and for 2-oxoglutarate of 2.82 mM and 0.28 mM, respectively, and pH-optimum around 8.0. Aspartate transaminase (= GOT) exhibited similar affinities for aspartate (Km = 2.55 mM) and for glutamate (Km = 3.13 mM), but clearly different Km-values for 2-oxoglutarate (1.46 mM) and for oxaloacetate (0.13 mM). Activity at optimum pH of about 8.0 was 506 nmol x mg protein(-1) x min(-1) for aspartate conversion, but only 39 nmol x mg protein(-1) x min(-1) at optimum pH of about 7.0 for glutamate conversion. Activity (599 nmol x mg protein(-1) x min(-1)), substrate affinities (Km for alanine = 6.30 mM, for 2-oxoglutarate = 0.45 mM) and pH-optimum (6.5-7.5) proved alanine transaminase (= GPT) also important in distribution of intracellular nitrogen. There was comparatively low activity of the obviously constitutive enzyme, urease, (42 nmol x mg protein(-1) x min(-1)) whose substrate affinity was rather high (Km = 0.56 mM). Nitrate reductase proved substrate induced; activity could only be measured after exposure of the mycelia to exogenous nitrate. Routes of entry of exogenous nitrogen and tentative significance of the various enzymes in cell metabolism are discussed.
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PMID:Investigations into enzymes of nitrogen metabolism of the ectomycorrhizal basidiomycete, Suillus bovinus. 1081 9


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