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)

Forty-three male mongrel dogs (12.5 +/- 2.5 kg) were divided into normal control (n = 7), immediate infusion (n = 8), non-infusion (n = 13) and delayed infusion (n = 15) groups. A 50% TBSA third degree surface burn was produced by igniting 3% napalm for 30 seconds on the shaved back. Cardiac, pulmonary, hepatic, renal and gastrointestinal functions were monitored following the thermal injury. The findings of these studies showed that mean arterial pressure, cardiac index, left ventricular work, right ventricular work, ADP/O ratio and ATP were all significantly decreased (P less than 0.05). However pulmonary artery wedge pressure, pulmonary vascular resistance, systemic vascular resistance, P(A-a)O2, Beef, Cr, UN, ALT, LDH, TB, DB, and MDA were markedly increased (P less than 0.05). Severe shock occurred soon after burns. Thirteen dogs died within 12 hours in the non-infusion group. All the dogs were resuscitated when immediate infusion of lactic acid Ringers solution was given according to Parkland formula, and all of them tide over shock stage smoothly without obvious changes in visceral functions. However, dogs were not resuscitated when infusion was delayed 6 hours postburn. The changes in visceral were even more severe in this group than those in non-infusion group. These results demonstrated that delayed resuscitation was an important factor of MOF in the early postburn stage. The marked increase in MDA in the myocardiac, lung, liver, renal and gastrointestinal tissues indicated that lipoperoxidation by free oxygen radicals was closely related with visceral damages.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Experimental study on early multiple organ failure after severe burns]. 159 85

The purine nucleotide content of lymphocytes of normal subjects and asymptomatic HIV-1 seropositive patients was analyzed by HPLC. An increase in IMP and a decrease in ADP, GDP, ATP and GPT were observed in the HIV-infected patients with respect to healthy subjects. The changes may depend on different factors and indicate that the virus influences purine nucleotide metabolism of the cell. The finding sheds light on the metabolic situation of the infected cell, and could be applied to monitoring the disease.
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PMID:Purine nucleotide content of lymphocytes from healthy subjects and asymptomatic HIV-1 seropositive patients. 176 29

To investigate the effect of extrahepatic cholestasis on integrity of the inner mitochondrial membrane, a study was conducted on two groups of rats: sham-operated control animals (N = 10) and rats subjected to extrahepatic cholestasis (EHC, N = 10) by double ligation of the hepatic duct. The animals were observed for 7 days and then sacrificed. The EHC group presented significantly higher serum levels of alanine aminotransferase, total bilirubins and alkaline phosphatase than the controls (P less than 0.01). Basal mitochondrial respiration (state IV), analyzed separately using either alpha-ketoglutarate or alpha-ketoglutarate + pyruvate as substrates, was similar in the two groups (P greater than 0.01). ADP-activated respiration, state III, diminished significantly in the EHC group. The results show that the decrease in mitochondrial function that has been reported by several investigators to occur in EHC is due to mitochondrial alterations not related to the ability of these organelles to maintain the proton gradient, since the inner mitochondrial membrane continued to be energized throughout the observation period.
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PMID:Integrity of liver inner mitochondrial membrane in rats with extrahepatic cholestasis. 182 30

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

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. 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

The effects of a new drug, N-2-(p-chlorophenoxy)-isobutyryl-N'-morpholinomethylurea (plafibride, ITA 104), were studied in a double blind study lasting four months on a group of 30 patients with a type IV hyperlipoproteinemia. In the patients treated with the active drug significant reductions in blood triglycerides were obtained, with a trend to normal. Reduction in blood cholesterol was inconsistent and not significant. As for the lipoproteinogram, a tendency towards a decrease in the pre-beta-lipoprotein fraction was observed and so was a non-significant tendency towards an increase in the alpha- and beta-lipoprotein fractions. Studies on the platelet functioning showed an obvious decrease in platelet aggregation in those patients treated with the active drug. This was very evident for the ADP and adrenaline inductors and rather less significant for collagen. Neither platelet adhesiveness nor aggregation rate changed. Tolerance of the drug was generally excellent. In one patient a decrease in some palpebral xanthelasmas was observed after two months of treatment with the active drug. In only one case there was heartburn and this was corrected with alkalines. In one other case an urticarial rash appeared, but disappeared spontaneously when the drug was temporarily stopped and did not reappear when it was administered again. During the trial no evidence of renal, hepatic or hematological malfunctions were observed. However, a slight tendency towards an increase in the GOT, GPT and LDH was observed, which was not statistically significant. The drug tested may be very useful in the treatment of type IV hyperlipoproteinemia, especially in those forms in which an increase in thromboembolic risk is suspected, either associated with, or secondary to, the actual atherosclerotic disease.
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PMID:Double-blind study on the activity of plafibride in the treatment of type IV hyperlipoproteinemia. 703 33

The author carried out a dynamic study on the metabolic changes in liver under the influence of nicotinic acid, administered singly by intramuscular injection in a dose of 2mM/kg of body weight. She examined at the 1th, 3th, 6th and 24th hour the changes in the levels of nicotine-amide coenzymes (NAD, NAD-H and NADP), adenine nucleotides (ATP, ADP and AMP), the metabolic lactate and pyruvate and the enzymes LDH, MDH, GOT and GPT. The obtained data were compared with those of the control groups, treated with saline and killed at the same intervals as the experimental animals. Furthermore she made also a comparison with an intact group, presented as O group, whose values served as basal. The obtained data showed that after application of the nicotinic acid (NA) complex metabolic changes occurred in liver, due to its basic effects-stimulation of biosynthesis of nicotinamide coenzymes and inhibition of lipolysis in the fatty tissue. Most probably the effect on the biosynthesis of NAD was primary, which showed later substantial regulatory influence both on lipolysis in the fatty acid and on the metabolization of mobilizing lipids on behalf of the liver. Parallel occurring metabolic processes in the aorta and in the vascular wall in general, stimulation of the biological oxidation and bioenergetics formed the whole antilipolytic and antiarteriogenic action of nicotinic acid.
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PMID:[Metabolic changes in the liver as affected by nicotinic acid]. 730 22

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


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