Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Titrations of mitochondrial apo-aspartate aminotransferase with pyridoxal 5'-phosphate in the presence of AMP, contrary to what has been observed in the case of the cytosolic isoenzyme [(1983) FEBS Lett. 153, 98-102], show sigmoidal isotherms, with Hill coefficients ranging from nH = 1.4, in the absence of AMP, to nH = 1.8, in the presence of 5.9 mM AMP. The experimental data were successfully fitted by the Monod-Wyman- Changeaux model. The best fit, in the absence of AMP, was obtained with L = 30, KR = 4.72 X 10(-7) M and KT = 1.18 X 10(-5) M. Binding curves in the presence of AMP fit the model by keeping KR as a constant. This implies that AMP could bind to the apoenzyme only in the T state. In contrast, binding curves in the presence of phosphate ion (Pi) showed a less pronounced cooperativity, the Hill coefficient dropping to nH = 1.0 in the presence of 0.1 mM Pi. The above results suggest a regulatory role of AMP and Pi in the reconstitution of aspartate aminotransferase.
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PMID:Cooperative effects in the binding of pyridoxal 5'-phosphate to mitochondrial apo-aspartate aminotransferase. 672 65

Interaction of cytosolic apo-aspartate aminotransferase with AMP has been studied under equilibrium conditions; e.g., equilibrium dialysis and spectrophotometric titration. Results show that a 1:1 stoichiometric complex AMP-apo-aspartate aminotransferase monomer is formed. The calculated dissociation constants with the two different experimental techniques are 40.4 x 10(-6) M-1 and 31.4 x 10(-6) M-1, respectively. These findings substantiate a previous hypothesis of control of the reconstitution of cytosolic apo-aspartate aminotransferases exerted by AMP.
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PMID:Interaction of AMP with cytosolic apo-aspartate aminotransferase. 682 64

The liver has been judged relatively resistant to ischemia, but prolonged inflow occlusion at normothermic conditions can produce evidence of reversible or irreversible hepatocellular damage. Cytoprotective agents have been used both experimentally and clinically to afford extended viability of hepatocytes under reduced perfusion. One agent, prostaglandin E1, has been described clinically as effective in sustaining liver function under ischemic conditions. We have sought to verify this observation in an experimental model using prolonged normothermic inflow occlusion. Twenty miniature pigs were anesthetized and subjected to subtotal normothermic hepatic inflow occlusion (portal vein, hepatic artery, choledochal vessels) to allow for sufficient splanchnic decompression. Half of the animals received pretreatment with prostaglandin E1 (alprostadil) 500 micrograms intravenously. Inflow occlusion was maintained for 2 hours followed by reperfusion and killing 24 hours later. As a measure of functional preservation, the tissue adenine nucleotides adenosine monophosphate, diphosphate, and triphosphate (AMP, ADP, ATP) were measured in ischemic liver by freeze-clamping and high-performance liquid chromatography during occlusion and after reperfusion. Cytosolic enzyme determinations (aspartate transaminase, alanine transaminase, lactate dehydrogenase) were also made before occlusion and after reperfusion. As a possible indicator of cellular injury, blood ionized Ca++ was measured before inflow occlusion and after reperfusion. Although no difference was found in levels of AMP and ADP between prostaglandin E1 and control animals, ATP levels rose significantly higher during recovery in prostaglandin E1 animals at 60 minutes and 24 hours after reperfusion (13.97 +/- 1.29 and 13.60 +/- 0.91 mumoles/gm dry weight prostaglandin E1 vs. 9.25 +/- 0.97 and 9.80 +/- 0.85 mumoles/gm dry weight co control, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of prostaglandin E1 on liver adenine nucleotides and cytoplasmic enzymes in a porcine model of normothermic hepatic ischemia. 759 Jun 75

To better characterize the role of skeletal muscle in chronic heart failure we studied energetic charge, metabolites and enzyme activity in the energy production pathway. We selected 15 males with severe chronic heart failure (NYHA class III, stable clinical conditions and in normal nutritional status) and seven controls. Controls and patients were submitted to biopsy of the vastus lateralis muscle in resting and fasting conditions. Hormone profiles were also evaluated. Our results showed near normal ATP, ADP and AMP concentrations, but there were substantially more reductions in glycogen (46 +/- 5 vs 77 +/- 6 mumoles glycosidic units.g-1 fresh tissue) and creatine phosphate (5 +/- 1 vs 13 +/- 1 mumoles.g-1 fresh tissue) in patients than in controls. We also found a reduction in glycolytic activity (pyruvate kinase 1009 +/- 79 vs 1625 +/- 26 nmoles. min-1.mg protein-1), despite normal tricarboxylic acid cycle velocity, an increase in alanine amino-transferase (964 +/- 79 vs 425 +/- 34 nmoles. min-1.mg protein-1) and in aspartate aminotransferase (515 +/- 44 vs 291 +/- 56 nmoles.min-1.mg protein-1). An increase was also observed in total NADH cytochrome c reductase (128 +/- 14 vs 68 +/- 5 nmoles.min-1.mg protein-1), while cytochrome oxidase activity was normal. The cortisol/insulin ratio was slightly elevated (77 +/- 4 vs 32 +/- 12). In conclusion, normonutritive patients with severe heart failure show an imbalance in the energy production/utilization ratio. The impairment is probably due both to a decrease in production and an increase in consumption of energy owing to greater cellular workload and/or a hypercatabolic state.
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PMID:Biochemical analysis of muscle biopsy in overnight fasting patients with severe chronic heart failure. 892 17

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

A gap junction is the channel for cell-to-cell communication and plays an important role in the maintenance of tissue homeostasis, control of cell growth and differentiation, and prevention of experimental hepatocarcino-genesis. Irsogladine, an antiulcer drug, augments gap junctional intercellular communication in gastric mucosa, but the effect of irsogladine on the liver remains uncertain. In this study the effects of irsogladine on the liver were investigated from the viewpoints of gap junctional protein connexin (Cx)32 and Cx26 in rats. Twelve rats were divided into a control group (n=6) and the irsogladine group (n=6) in which irsogladine (20 mg/kg per day) was administered orally for 3 days before sample collection, and the two groups were compared in regard to liver enzymes (serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH)), serum- and tissue-calcium concentrations, immunohistochemical expressions of Cx32 and Cx26, and RT-PCR analysis. In immunohistochemistry, analyzed using an image processor for analytical pathology (IPAP), the number of Cx32-positive spots was higher and the area of Cx26-positive spots were larger in the irsogladine group than those in the control group (P=0.036 and P=0.00032, respectively). In RT-PCR analysis, the mRNA of Cx32 or Cx26 in the irsogladine group showed a tendency to be higher than in the control group, but not significantly (Cx32, P=0.70; Cx26, P=0.07). Another 30 rats were used for measurements of cyclic-adenosine monophosphate (c-AMP) of the liver. c-AMP concentration was increased 1 h after the administration of irsogladine, which partially explained how the Cxs were upregulated. These findings may suggest that irsogladine upregulates Cx32 and Cx26 expressions in the liver of rats.
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PMID:Irsogladine upregulates expressions of connexin32 and connexin26 in the rat liver. 1083 34

We investigated whether the imposition of chronic alcohol in hypertension leads to greater biochemical and cellular abnormalities of the myocardium than those arising in normotension. Fifteen-week-old spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were fed ethanol-containing diets for six weeks. Particular attention was focused on the composition of contractile proteins identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), fractional rate of protein synthesis, and synthesis rates relative to RNA (RNA activity) or DNA (cellular efficiency). In addition, myocardial enzymes and adenine nucleotides were measured. In both SHR and WKY rats chronic ethanol caused a general decrease in the contents of all nine contractile proteins with myosin heavy chain predominantly affected. Fractional rates of mixed (i.e., total) and myofibrillary proteins remained unaltered in both WKY rats and SHR, as were cellular efficiencies. The RNA activity was significantly reduced in ethanol-treated SHR but not in WKY rats. In ethanol-treated SHR, cardiac creatine kinase (CK) and malate dehydrogenase (MDH) activities were increased, AMP levels were elevated, whilst ATP levels and the energy charge were reduced. In WKY rats, the only significant change related to increased aspartate aminotransferase activities in response to alcohol feeding. Although there were only subtle differences between the response of the normotensive and hypertensive rats due to ethanol dosage, the reduced ATP levels and increased CK and MDH activities in SHR may reflect a greater susceptibility to ischaemic damage. Reduced contractile protein content, particularly myosin heavy chain, may contribute to contractile defects, a common feature of subclinical and clinical alcoholic cardiomyopathy.
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PMID:A comparative investigation into the effect of chronic alcohol feeding on the myocardium of normotensive and hypertensive rats: an electrophoretic and biochemical study. 1093 59

Reactive oxygen species generated by xanthine oxidase during reperfusion of ischemic liver might in part be responsible for ischemic organ injury. In normothermic ischemia/reperfusion rat model, we investigated whether allopurinol pretreatment improved ischemia-induced mitochondrial dysfunction. Rats were subjected to 60 min of hepatic ischemia and to 1 h and 5 h of reperfusion thereafter. At 18 h and 1 h before ischemia, the animals received 0.25 mL of either saline or allopurinol (50 mg/kg) i.p. In saline-treated ischemic rats, serum aspartate aminotransferase levels increased significantly at 5 h (4685 +/- 310 IU/L) and were significantly reduced with allopurinol pretreatment. Similarly, mitochondrial lipid peroxidation was elevated in the saline-treated ischemic group, but this elevation was prevented by allopurinol. In contrast, mitochondrial glutamate dehydrogenase activity and ketone body ratio decreased in the saline-treated group, but this decrease was also inhibited by allopurinol. Hepatic ATP levels in the saline-treated rats were 42% lower 5 h after reperfusion. However, treatment with allopurinol resulted in significantly higher ATP levels. Allopurinol treatment preserved the concentration of AMP in ischemic liver but inhibited the accumulation of xanthine in reperfused liver. Our findings suggest allopurinol protects against mitochondrial injury, which prevents a mitochondrial oxidant stress and lipid peroxidation and preserves the hepatic energy metabolism.
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PMID:Protective effect of allopurinol on hepatic energy metabolism in ischemic and reperfused rat liver. 1122 Jun 38

Isolated mongrel hearts were preserved for 6 h at 5 degrees C followed by normothermic reperfusion for 2 h. The dogs were divided into three groups; K+-cardioplegic solution alone, group C, n = 7; K+-cardioplegic solution with lidocaine 200 mg/l, group L, n = 7; and K+-cardioplegic solution with betamethasone 250 mg/l and lidocaine 200 mg/l, group B + L, n = 7. Ventricular fibrillation occurred early during reperfusion in all dogs in group C, in one of seven in group L, and in two of seven dogs in group B + L. The serum MB fraction of creatinine kinase (MB-CK), mitochondrial aspartate aminotransferase (m-AAT) and calcium overload were suppressed to a greater extent in both groups L and B + L during reperfusion compared to group C. Myocardial ATP, total adenine nucleotide, and creatine phosphate did not differ between the three groups at the end of reperfusion. Myocardial ADP and AMP declined significantly during reperfusion in group C, however, they remained unchanged in group B + L and increased in group L which showed significantly higher levels compared to group C. Left ventricular functional recovery during reperfusion was consistently better in both group L and B + L compared to group C. These results suggested that membrane stabilization prevents myocardial damage from hypothermia and cardioplegia and provides better myocardial viability and functional recovery in donor heart preservation.
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PMID:The significant role of membrane stabilization in hypothermic cardioplegic cardiac preservation in a canine experimental model. 1462 34

The interaction of the precursor to mitochondrial aspartate aminotransferase (pmAAT) with GroEL has been studied by electron paramagnetic resonance (EPR) and fluorescence spectroscopy. In the native protein, the spin probe was immobilized when attached to Cys166 at the domain interface, but was fully mobile when introduced at Cys(-19) in the N-terminal presequence peptide. Unfolding of the protein resulted in a highly mobile EPR spectrum for probes introduced at either site. However, the nitroxide group in GroEL-bound pmAAT showed either intermediate or high mobility depending on the spin probe used. Power saturation experiments indicated that the accessibility of the nitroxide side chain to Ni(EDDA) in the GroEL-pmAAT complex was higher than in the native state when in position 166 but lower when at position -19. Similar results were obtained in fluorescence quenching experiments. These data suggest that GroEL binds partly folded states of pmAAT with the presequence peptide probably in direct contact with GroEL. GroES and ATP, but not AMP-PNP or ADP, support refolding of pmAAT. During refolding, the rate of recovery of the native spectroscopic properties of labeled Cys166 is nearly identical to the rate-limiting reactivation step. Thus, correct docking of the large and small domains of pmAAT may be a key structural event in the regain of catalytic activity.
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PMID:Electron paramagnetic resonance and fluorescence studies of the conformation of aspartate aminotransferase bound to GroEL. 1632 39


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