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)

Oxygen free radicals have been implicated in the pathogenesis of postischemic liver injury. High-dose superoxide dismutase (SOD), a radical scavenging enzyme, has been investigated in a rat model of liver ischemia reperfusion by biochemical monitoring. Blood vessels to the median and left lobe were clamped for 1 h and then reperfusion was allowed. The indices used were serial venous blood levels of AST, ALT, calcium, and ATP determination in liver tissue. In SOD-treated animals (7,5000 U i.v.) a significant attenuation of the rise in enzyme levels was observed as well as the absence of the decrease in calcium level in the early phase after reperfusion as compared with control rats, and furthermore ATP restoration was significantly increased.
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PMID:Effect of superoxide dismutase on liver ischemia-reperfusion injury in the rat: a biochemical monitoring. 322 31

Hepatic function was assessed by the aminopyrine breath test (ABT) in male Sprague Dawley rats 24 h after partial hepatic ischemia. ABT decreased progressively to 26.3 (p less than 0.05) and 19.7% of dose (p less than 0.05) after 90 and 120 min of ischemia, respectively. ABT at 24 h after injury was correlated to the concentration of ATP in the ischemic lobes 1 h after the onset of reperfusion (r2 = 0.971) but not to ALT activity in plasma at 1 h (r2 = 0.391). We conclude that postischemic ATP levels are a better index of subsequent hepatic function than ALT.
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PMID:Postischemic ATP levels predict hepatic function 24 hours following ischemia in the rat. 337 51

The effects of total ischemia and subsequent reperfusion on the formation of anaerobic metabolism products and their release into myocardial effluent were studied in isolated guinea pig hearts. During 30-min ischemia myocardial ATP and phosphocreatine decreased to 34 and 15% of the initial levels, respectively; this was accompanied by alanine formation and approximately stoichiometric glutamate loss. The increase in malate in ischemic myocardium corresponded to the anaplerotic flux aspartate----oxaloacetate----malate; the succinate production being commensurable to alpha-ketoglutarate formation in the alanine aminotransferase reaction. The release of lactate, alanine, succinate, creatine and pyruvate trace amounts into the myocardial effluent was observed during an early phase of the reperfusion using 1H-NMR. The rates of metabolite release reduced as follows: lactate much greater than alanine greater than succinate greater than creatine. By the 30th min of the reperfusion the decrease in these metabolites tissue contents was accompanied by the recovery of ATP and phosphocreatine levels up to 65 and 90% of the initial ones, respectively. The data obtained demonstrate that the formation and the release of succinate, alanine and creatine from the heart as well as of lactate may indicate profound disturbances in energy metabolism.
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PMID:An assessment of anaerobic metabolism during ischemia and reperfusion in isolated guinea pig heart. 337 59

The effect of ischemia on the formation of products of anaerobic metabolism and their release into the cardiac effluent in isolated perfused guinea pig hearts was studied. During 30 min normothermal ischemia, the myocardial ATP and phosphocreatine levels decreased to 34% and 15% of the initial values, respectively. The net alanine formation in ischemia was approximately a stoichiometric glutamate decrease; the increase in the tissue malate content corresponded to the aspartate----oxaloacetate----malate anaplerotic flux, the succinate production being commensurable to alpha-ketoglutaric acid formation in the alanine aminotransferase reaction. Using 1H-NMR, it was shown that the release of trace amounts of lactate, alanine, succinate, creatine and pyruvate into cardiac effluents occurred during the first 5 minutes of reperfusion. The rate of metabolite release decreased in the following order: lactate much greater than alanine greater than succinate greater than creatine. By the 30th minute of reperfusion, the decrease in the tissue levels of these metabolites to preischemic values was accompanied by the recovery of ATP and phosphocreatine to 65% and 90% of the initial levels, respectively. The data obtained suggest that the formation and release of alanine, creatine or succinate as well as lactate from ischemic myocardium may testify to significant disturbances in energy metabolism of the myocardium.
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PMID:[Formation of products of anaerobic metabolism in the ischemic myocardium]. 337 64

A previously described digitonin-perfusion technique [Quistorff, Grunnet & Cornell (1985) Biochem. J. 226, 289-297], by which intracellular material of rat liver could be liberated, has been refined, now allowing release of cytosol of high purity from both periportal and perivenous parts of the same liver. The cytosolic fractions are obtained by perfusing the liver for short intervals (10-20 s) with digitonin (4-5 mg/ml), first in the normal perfusion direction and then, after an interval of 1-2 min, in the retrograde direction, the eluate being collected during and after both intervals. The technique is termed 'dual-digitonin-pulse perfusion'. The eluate fractions showed a peak specific activity of the cytosolic enzymes alanine aminotransferase (ALAT), lactate dehydrogenase (LDH) and pyruvate kinase (PK) of 3-5-fold higher than obtained in a biopsy from the same liver. For glutamine synthetase (GS) a 10-fold higher specific activity was obtained. Zonation, defined as the ratio of the specific activities in periportal and perivenous eluates, of ALAT, LDH and PK was 10, 1.7 and 0.70 respectively. Zonation of GS was less than 0.01. These factors may be modified by a slight zonation of cytosolic protein of 1.2-1.3. Peak concentrations in the eluate of ATP, ADP, Pi, NAD+ and glycerol 3-phosphate were 32.5 +/- 11.4, 19.9 +/- 4.3, 71.9 +/- 25.4, 2.41 +/- 0.83 and 6.84 +/- 2.74 nmol/mg of protein for periportal eluates. There was no difference between periportal and perivenous eluates except for glycerol 3-phosphate, which was significantly higher in perivenous eluates, 12.8 +/- 4.5 nmol/mg of protein.
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PMID:Dual-digitonin-pulse perfusion. Concurrent sampling of periportal and perivenous cytosol of rat liver for determination of metabolites and enzyme activities. 360 84

Biochemical changes in the placenta were studied using alloxan-induced diabetes mellitus in the female rat. In comparison with a control group (n = 13) the placentas of the diabetic animals (n = 12) had significantly higher glucose, glycogen and protein levels. It was, however, shown that this supply of substrate was inadequately utilised for energy, as ATP/ADP quotient was lower and the ADP content was significantly higher. Metabolism still appeared to take place under aerobic conditions, as evidenced by the unchanged lactate levels. In terms of the protein content of the placentas, the activity of the enzymes we investigated (GOT, GPT, LDH, G-6-PDH, MDH, ICDH) was lowered by 25-44%. These results support the idea of global placental insufficiency in diabetics.
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PMID:Effects of alloxan-induced diabetes mellitus on the metabolism of the rat placenta. 395 50

In a previous study, we showed that methotrexate (MTX) enhanced the intracellular production of ara-CTP. The study described in the present paper has elucidated the mechanism of this MTX-enhanced ara-CTP production, which occurs as a result of MTX reducing the intracellular dCTP pool, and the decreased dCTP pool then allowing activation of deoxycytidine Kinase. One of the mechanisms of synergistic interaction between 1-beta-D-arabinofuranosylcytosine (ara-C) and MTX might therefore be the stimulated phosphorylation of ara-C with MTX-activated deoxy-cytidine kinase. Using high-pressure liquid chromatography, the sequential changes occurring in the acid-soluble intracellular nucleotide pools of L1210 mouse leukemic cells were analysed after treatment with MTX (12mg/kg). At 3 hr after treatment with MTX a reduction of the dTTP pool to 46% of the control level was observed. The dCTP pool was also reduced to 36% of the control level after treatment with MTX. The levels of the dATP and dGTP pools were not significantly changed, at least during the observation period. Pyrimidine ribonucleotide pools were almost unchanged at 3 hr, but in the sequential changes observed in purine ribonucleotide pools after treatment with MTX, both diphosphate and triphosphate pools were seen to be on the decline, the reduction of triphosphate pools being especially marked. A decline in ATP and GPT to 24-30% of control levels was observed at 3 hr after treatment with MTX.
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PMID:[The effect of methotrexate on intracellular nucleotide pools]. 403 17

1. Changes in the concentrations of ammonia, glutamine, glutamate, 2-oxoglutarate, 3-hydroxybutyrate, acetoacetate, alanine, aspartate, malate, lactate, pyruvate, NAD(+), NADH and adenine nucleotides were measured in freeze-clamped rat liver during ischaemia. 2. Although the concentrations of most of the metabolites changed rapidly during ischaemia the ratios [glutamate]/[2-oxoglutarate][NH(4) (+)] and [3-hydroxybutyrate]/[acetoacetate] changed equally and the value of the expression [3-hydroxybutyrate][2-oxoglutarate][NH(4) (+)]/[acetoacetate][glutamate] remained approximately constant, indicating that the 3-hydroxybutyrate dehydrogenase and glutamate dehydrogenase systems were at near-equilibrium with the mitochondrial NAD(+) couple. 3. The value of the expression [alanine][oxoglutarate]/[pyruvate][glutamate] was about 0.7 in vivo and remained fairly constant during the ischaemic period of 5min, although the concentrations of alanine and oxoglutarate changed substantially. No explanation can be offered why the value of the ratio differed from that of the equilibrium constant of the alanine aminotransferase reaction, which is 1.48. 4. Injection of l-cycloserine 60min before the rats were killed increased the concentration of alanine in the liver fourfold and decreased the concentration of the other metabolites measured, except that of pyruvate. During ischaemia the concentration of alanine did not change but that of aspartate almost doubled. 5. After treatment with l-cycloserine the value in vivo of the expression [alanine][oxoglutarate]/[pyruvate][glutamate] rose from 0.7 to 2.4. During ischaemia the value returned to 0.8. 6. The effects of l-cycloserine are consistent with the assumption that it specifically inhibits alanine aminotransferase. 7. Most of the alanine formed during ischaemia is probably derived from pyruvate and from ammonia released by the deamination of adenine nucleotides and glutamine. The alanine is presumably formed by the combined action of glutamate dehydrogenase and alanine aminotransferase. 8. The rate of anaerobic glycolysis, calculated from the increase in the lactate concentration, was 1.3mumol/min per g fresh wt. 9. Although the concentrations of the adenine nucleotides changed rapidly during ischaemia, the ratio [ATP][AMP]/[ADP](2) remained constant at 0.54, indicating that adenylate kinase established near-equilibrium under these conditions.
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PMID:Effects of ischaemia on metabolite concentrations in rat liver. 431 90

1. Mitochondrial and supernatant aspartate transaminases (EC 2.6.1.1) and supernatant alanine transaminase (EC 2.6.1.2) were purified 89-, 204- and 240-fold respectively, from dolphin muscle. Starch-gel electrophoresis of crude and purified preparations revealed that all three enzymes exist as single forms. 2. K(m) values of alpha-oxoglutarate, alanine, pyruvate and glutamate for the alanine transaminase were 0.45, 8.2, 0.87 and 15mm respectively. For the aspartate transaminases, the K(m) values of alpha-oxoglutarate, aspartate, oxalacetate and glutamate were 0.76, 0.50, 0.10 and 9.4mm respectively, for the mitochondrial form and 0.13, 2.4, 0.06 and 3.2mm respectively, for the supernatant form. 3. In all cases, as the assay pH value was decreased from pH7.3, the K(m) values of the alpha-oxo acids decreased whereas those of the amino acids increased. 4. The apparent equilibrium constants for the aspartate transaminases were independent of pH. These values were 9.2 and 6.8 for the mitochondrial and supernatant forms respectively, where [Formula: see text] 5. Studies of the inhibition of the aspartate transaminases by dicarboxylic acids indicated that these enzymes may be controlled by pools of metabolic intermediates. 6. Three key roles are suggested for the transaminases in the energy metabolism of the diving animal. First, it is believed that a combined action of the transaminases could enhance energy production during hypoxia by providing (a) fumarate from aspartate for the ATP-producing reversal of succinate dehydrogenase, and (b) alpha-oxoglutarate from glutamate for the GTP-producing succinyl thiokinase reaction. Secondly, diving mammals probably accumulate more NADH than other mammals during hypoxia. The aspartate transaminases seem particularly well suited for restoring and maintaining redox balance via the malate-aspartate cycle after aerobic metabolism is resumed. Finally, since the preferred fuel for aerobic work is fat, the combined reactions of the transaminases could be instrumental in providing increased supplies of oxaloacetate for sparking the tricarboxylic acid cycle.
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PMID:Purification and properties of dolphin muscle aspartate and alanine transaminases and thier possible roles in the energy metabolism of diving mammals. 446 40

1. Transient and steady-state changes caused by acetate utilization were studied in perfused rat heart. The transient period occupied 6min and steady-state changes were followed in a further 6min of perfusion. 2. In control perfusions glucose oxidation accounted for 75% of oxygen utilization; the remaining 25% was assumed to represent oxidation of glyceride fatty acids. With acetate in the steady state, acetate oxidation accounted for 80% of oxygen utilization, which increased by 20%; glucose oxidation was almost totally suppressed. The rate of tricarboxylate-cycle turnover increased by 67% with acetate perfusion. The net yield of ATP in the steady state was not altered by acetate. 3. Acetate oxidation increased muscle concentrations of acetyl-CoA, citrate, isocitrate, 2-oxoglutarate, glutamate, alanine, AMP and glucose 6-phosphate, and lowered those of CoA and aspartate; the concentrations of pyruvate, ATP and ADP showed no detectable change. The times for maximum changes were 1min, acetyl-CoA, CoA, alanine and AMP; 6min, citrate, isocitrate, glutamate and aspartate; 2-4min, 2-oxoglutarate. Malate concentration fell in the first minute and rose to a value somewhat greater than in the control by 6min. There was a transient and rapid rise in glucose 6-phosphate concentration in the first minute superimposed on the slower rise over 6min. 4. Acetate perfusion decreased the output of lactate, the muscle concentration of lactate and the [lactate]/[pyruvate] ratio in perfusion medium and muscle in the first minute; these returned to control values by 6min. 5. During the first minute acetate decreased oxygen consumption and lowered the net yield of ATP by 30% without any significant change in muscle ATP or ADP concentrations. 6. The specific radioactivities of cycle metabolites were measured during and after a 1min pulse of [1-(14)C]acetate delivered in the first and twelfth minutes of acetate perfusion. A model based on the known flow rates and concentrations of cycle metabolites was analysed by computer simulation. The model, which assumed single pools of cycle metabolites, fitted the data well with the inclusion of an isotope-exchange reaction between isocitrate and 2-oxoglutarate+bicarbonate. The exchange was verified by perfusions with [(14)C]bicarbonate. There was no evidence for isotope exchange between citrate and acetyl-CoA or between 2-oxoglutarate and malate. There was rapid isotope equilibration between 2-oxoglutarate and glutamate, but relatively poor isotope equilibration between malate and aspartate. 7. It is concluded that the citrate synthase reaction is displaced from equilibrium in rat heart, that isocitrate dehydrogenase and aconitate hydratase may approximate to equilibrium, that alanine aminotransferase is close to equilibrium, but that aspartate transamination is slow for reasons that have yet to be investigated. 8. The slow rise in citrate concentration as compared with the rapid rise in that of acetyl-CoA is attributed to the slow generation of oxaloacetate by aspartate aminotransferase. 9. It is proposed that the tricarboxylate cycle may operate as two spans: acetyl-CoA-->2-oxoglutarate, controlled by citrate synthase, and 2-oxoglutarate-->oxaloacetate, controlled by 2-oxoglutarate dehydrogenase; a scheme for cycle control during acetate oxidation is outlined. The initiating factors are considered to be changes in acetyl-CoA, CoA and AMP concentrations brought about by acetyl-CoA synthetase. 10. Evidence is presented for a transient inhibition of phosphofructokinase during the first minute of acetate perfusion that was not due to a rise in whole-tissue citrate concentration. The probable importance of metabolite compartmentation is stressed.
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PMID:Control of the tricarboxylate cycle and its interactions with glycolysis during acetate utilization in rat heart. 544 22


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