Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The generation of C2- and C3-deuterated L-lactate was monitored by 13C NMR in human erythrocytes exposed to D-[1-13C]glucose, D-[2-13C]glucose or D-[6-13C]glucose and incubated in a medium prepared in D2O. 2. The results suggested that the deuteration of the C1 of D-fructose 6-phosphate in the phosphoglucoisomerase reaction, the deuteration of the C1 of D-glyceraldehyde-3-phosphate in the sequence of reactions catalyzed by triose phosphate isomerase and aldolase and the deuteration of the C3 of pyruvate in the reaction catalyzed by pyruvate kinase were all lower than expected from equilibration with D2O. 3. Moreover, about 40% of the molecules of pyruvate generated by glycolysis apparently underwent deuteration on their C3 during interconversion of the 2-keto acid and L-alanine in the reaction catalyzed by glutamate-pyruvate transaminase. 4. The occurrence of the latter process was also documented in cells exposed to exogenous [3-13C]pyruvate. 5. This methodological approach is proposed to provide a new tool to assess in intact cells the extent of back-and-forth interconversion of selected metabolic intermediates.
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PMID:Generation of C3- and C2-deuterated L-lactic acid by human erythrocytes exposed to D-[1-13C]glucose, D-[2-13C]glucose and D-[6-13C]glucose in the presence of D2O. 800 54

The production of C3-trisdeuterated, bisdeuterated, monodeuterated or non-deuterated L-[3-13C]lactate by human erythrocytes exposed to either D-[1-13C]glucose or D-[6-13C]glucose in the presence of 2H2O can be assessed by 13C NMR spectroscopy. Such a deuteration may occur at the level of the reactions catalyzed by phosphoglucoisomerase, phosphomannoisomerase, pyruvate kinase and glutamate-pyruvate transaminase. In this report, a mathematical model is proposed for the analysis of experimental data. It allows to estimate the relative extent of deuteration at each step of D-glucose metabolism. This approach may thus provide novel information on the extent of back-and-forth interconversion of either hexose 6-phosphates in both the phosphoglucoisomerase and phosphomannoisomerase reactions or pyruvate and L-alanine in the reaction catalyzed by glutamate-pyruvate transaminase.
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PMID:Mathematical modelling for the generation of L-[3-2H,3-13C]lactic acid isotopomers by erythrocytes exposed to either D-[1-13C]glucose or D-[6-13C]glucose in the presence of 2H2O. 802 92

Epimastigotes of Trypanosoma cruzi, the causative agent of Chagas disease, catabolize proteins and amino acids with production of MH3, and glucose with production of reduced catabolites, chiefly succinate and L-alanine, even under aerobic conditions. This "aerobic fermentation of glucose" is probably due to both the presence of low levels of some cytochromes, causing a relative inefficiency of the respiratory chain for NADH, reoxidation during active glucose catabolism, and the lack of NADH dehydrogenase and phosphorylation site I, resulting in the entry of reduction equivalents into the chain mostly as succinate. Phosphoenol pyruvate carboxykinase and pyruvate kinase may play an essential role in diverting glucose carbon to succinate or L-alanine, and L-malate seems to be the major metabolite for the transport of glucose carbon and reduction equivalents between glycosome and mitochondrion. The parasite contains proteinase and peptidase activities. The major lysosomal cysteine proteinase, cruzipain, has been characterized in considerable detail, and might be involved in the host/parasite relationship, in addition to its obvious role in parasite nutrition. Among the enzymes of amino acid catabolism, two glutamate dehydrogenases (one NADP- and the other NAD-linked), alanine aminotransferase, and the major enzymes of aromatic amino acid catabolism (tyrosine aminotransferase and aromatic alpha-hydroxy acid dehydrogenase), have been characterized and proposed to be involved in the reoxidation of glycolytic NADH.
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PMID:Intermediate metabolism in Trypanosoma cruzi. 805 82

The capacity of the malate-aspartate shuttle was evaluated in periportal (PP-H) and perivenous subfraction of rat hepatocytes (PV-H). The rate of glutamine production from alanine was 34-fold higher in PV-H than in PP-H. Statistically significant differences between PP-H and PV-H were found for the activities of lactate dehydrogenase and pyruvate kinase but not for the activities of NAD(+)-malate dehydrogenase, aspartate aminotransferase, and mitochondrial alanine aminotransferase. The rate of glucose production from sorbitol and the rate of ethanol utilization were higher in PP-H than in PV-H. In the presence of phenazine methosulfate (PMS), the increments in these rates were significantly greater in PV-H than in PP-H. The capacity of malate-aspartate shuttle in the presence of alanine was significantly higher in PP-H than in PV-H but in the presence of asparagine was similar in PP-H and PV-H. The results suggest that the capacity of malate-aspartate shuttle distributes heterogeneously along liver lobules with the dominance in periportal zone and that the difference of the capacity may result from the difference in the transport of aspartate across the mitochondrial membrane.
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PMID:The capacity of the malate-aspartate shuttle differs between periportal and perivenous hepatocytes from rats. 810 64

Subclinical nutritional myopathy was induced in 5-month-old sheep by feeding them a diet low in vitamin E and selenium. Subsequently clinical myopathy was induced by dosing with protected polyunsaturated fatty acids. Plasma activities of creatine kinase (CK), pyruvate kinase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase and aldolase, enzymes of muscle origin, all remained above their reference ranges in clinically affected sheep, but fluctuated widely. Similar fluctuations occurred in subclinically affected animals, resulting in some activities being within the reference ranges and some above, at different times. Plasma malondialdehyde, an indicator of lipid peroxidation, proved of no diagnostic value. Terminal plasma CK activities were significantly correlated with microscopic damage in the vastus lateralis (VL), but not the vastus intermedius (VI) or the tensor fascia lata (TFL) muscles. AST was the most highly correlated with damage in VI and VL. In two clinically affected sheep successfully treated with an oral dose of alpha-tocopherol acetate all enzymes decreased steadily to within their reference ranges, at rates probably related to their plasma half-lives. These results suggest that measurement of plasma CK activity would be useful in monitoring recovery of treated sheep.
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PMID:Plasma indicators of muscle damage in a model of nutritional myopathy in weaner sheep. 817 46

Efficient energy utilization is essential for cell growth; in an attempt to improve the growth conditions of the rat T-lymphocyte culture model for potential use in studying the mutagenic activity of carcinogens in vitro, we have investigated the effects of phytohemagglutinin (PHA), interleukin-2 (IL-2) and 2-mercaptoethanol (2-ME) on the activities of intermediary metabolism enzymes and cell proliferation. Isolated lymphocytes were cultured in the presence and absence of PHA, IL-2, or 2-ME. The intermediary metabolism enzymes investigated were glutamate dehydrogenase, glutamate-pyruvate transaminase, malate dehydrogenase, isocitrate dehydrogenase, lactate dehydrogenase, pyruvate kinase, and fatty acid synthetase (FAS). Measurable activity of all enzymes investigated, except for FAS, was detected in PHA-stimulated cells cultured with IL-2 or 2-ME. The unstimulated lymphocytes had significantly lower enzyme activity than stimulated cells. The combination of all three agents showed increased enzyme activity. This increase in activity brought about by the combination of the three agents was not reproduced by either agent acting alone. In general, the increase in enzyme activity correlated with cell proliferation as measured by [3H]thymidine uptake in PHA-stimulated cultures containing IL-2 and/or 2-ME. The results suggest that the addition of exogenous IL-2 and 2-ME enhances metabolic function and may be beneficial in in vitro culture of rat lymphocytes.
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PMID:Characterization of rat lymphocyte primary culture for the development of an in-vitro mutagenesis assay: effect of interleukin-2 and 2-mercaptoethanol on the activities of intermediary metabolism enzymes and cell proliferation. 873 77

The activities of 18 enzymes involved in the intermediary and energy metabolism were measured in certain widely-spread peracarid crustaceans: 3 hypogean (Niphargus virei, Niphargus rhenorhodanensis and Stenasellus virei) and 2 epigean (Gammarus fossarum and Asellus aquaticus) ones. The activities of numerous enzymes were correlated with the known metabolic rates of the 5 species. Such rates are reduced in hypogean organisms: levels of enzymatic activity in subterranean species were 1.2 to 8.6 times lower than in epigean species for the main key regulatory enzymes involved in the Krebs cycle and glycolysis (phosphofructokinase, pyruvate kinase, hexokinase and citrate synthetase). The relative activities of phosphofructokinase, glycogen phosphorylase and hexokinase clearly indicated that glycogen was the main fuel oxidized in both epigean and hypogean organisms. A higher glycogen phosphorylase/hexokinase ratio in hypogean than in epigean crustaceans showed that subterranean species had a greater ability to function anaerobically. The presence of high activities of glutamate-pyruvate transaminase and lactate dehydrogenase in all species (and of malate dehydrogenase and fumarase in hypogean species) was indicative of a coupled fermentation of glycogen and glutamate during anaerobiosis, with lactate and alanine as end-products (as well as succinate in hypogean species). A low fructose-1,6-bisphosphatase/phosphofructokinase ratio, associated with a low level of phosphoenolpyruvate carboxykinase activity, indicated that the glycolytic pathway was active and that gluconeogenic ability was limited in epigean crustaceans. In contrast, in hypogean species, association of a higher ratio and a high level of phosphoenolpyruvate carboxykinase activity suggested a low glycolytic activity and a high gluconeogenic ability.
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PMID:The activities of enzymes associated with the intermediary and energy metabolism in hypogean and epigean crustaceans. 909 Nov 76

We measured enzyme activities along a heterothermic tissue, the visceral retia mirabilia of the bluefin tuna, to test current theories of enzyme temperature adaptation. The heterothermic tissue model is ideal for the study of fundamental temperature adaptation because it eliminates confounding effects of whole animal acclimation. Enzymes were measured at six positions along the rete at four temperatures (15, 20, 25, and 30 degrees C). Five enzymes (aspartate aminotransferase, citrate synthase, glucose-6-phosphate dehydrogenase, glutamate dehydrogenase, and pyruvate kinase) exhibited a significant positive compensatory effect, with activity at the cold end of the rete 1.2-3.1 times higher than at the warm end. Two enzymes (alanine aminotransferase and lactate dehydrogenase) exhibited no significant compensation. On the basis of activation energies of enzymes along the rete, differences in activity were due to differences in enzyme concentration and not isozymes or enzyme modification. Analysis of the compensatory responses of the enzymes in light of their thermal sensitivities leads us to conclude that the pentose phosphate shunt is especially enhanced at the cold end of the rete.
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PMID:Enzyme adaptation along a heterothermic tissue: the visceral retia mirabilia of the bluefin tuna. 922 97

Skeletal muscle biopsies were performed on 12 healthy sedentary subjects and on 22 non-dyalized chronic renal failure patients (CRF) on a free diet and after overnight fasting. Parathormone, glucagon and insulin were determined at the same time of biopsies. CRF patients showed significantly low ATP and creatine phosphate levels. Regarding enzyme activities, a high hexokinase Vmax was found, while the pyruvate kinase activity was lower than in the control group. For the tricarboxylic acid cycle, citrate synthase, succinate dehydrogenase and malate dehydrogenase activities were higher; total NADH cytochrome c reductase activity was also high, while cytochrome oxidase activity was slightly lower. Both alanine aminotransferase and aspartate aminotransferase activities were considerably high in comparison with the control group. In conclusion, our study revealed a hypermetabolic TCA cycle, but impaired oxidative phosphorylation, which partly explained the reduced ATP concentration. Excessive protein intake and hormonal derangements may play a role in these metabolic changes.
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PMID:Altered muscle energy metabolism in post-absorptive patients with chronic renal failure. 924 94

Experiments were performed on eight subjects affected by peripheral arterial occlusive disease (PAOD) of the lower limbs. Each patient was submitted to Ecodoppler, angiography and the "Treadmill test". Two bioptic muscle of these patients. A sample was used for the spectrophotometric and spectrophotofluorimetric determinations of: glycogen, pyruvate, lactate, citrate, alpha-ketoglutarate, malate, aspartate, glutamate, AMP, ADP, ATP and creatine phosphate (CP). The other bioptic sample was used to determine the following enzyme activities: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase, citrate synthase, succinate dehydrogenase, malate dehydrogenase, total NADH cytochrome c reductase, cytochrome oxidase, aspartate aminotransferase and alanine aminotransferase. Patients showed an increase in lactate dehydrogenase, total NADH cytochrome c reductase and succinate dehydrogenase activities, a decrease in glycogen, ATP and CP concentrations. Telethermographic data showed patient muscle thermic emission quantitatively different from control group. The telethermographic test can be used as an additional diagnostic tool to determine and monitor the efficiency of a muscle undergoing metabolic failure.
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PMID:Instrumental and metabolic evaluation of patients affected by peripheral arterial occlusive disease (PAOD) following surgical revascularization surgery. 928 78


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