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)

Factor analysis of admission data from 209 Reye's syndrome patients yielded three factors. Factor 1 was associated with encephalopathy, blood ammonia, creatinine kinase (CK), uric acid and, to a lesser extent, bilirubin. This factor was linked to the encephalopathy and hypermetabolic changes in muscle, possibly prostaglandin-mediated proteolysis. Factor 2 was associated with serum alanine aminotransferase (AlaAT) and aspartate aminotransferase (AspAT), and was identified as a hepatic lesion component. These factors correspond to two etiologic components of Reye's syndrome. Salicylate was only weakly associated with neuropathic and hypercatabolic indicators and not at all associated with the hepatic damage indicators.
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PMID:Hepatic and encephalopathic components of Reye's syndrome: factor analysis of admission data from 209 patients. 402 64

Discriminant analysis was used to discriminate between Reye syndrome (RS) patients and non-RS cases based either on conventional blood chemistry data obtained upon admission, or on the activities of hepatic mitochondrial enzymes in biopsy or necropsy tissue. The control group for blood chemistry measurements contained children with upper respiratory tract infections, varicella, etc. who did not develop RS, as well as healthy children. Subjects with no liver disorder (e.g., accidental death, sudden infant death, etc.) or with non-RS liver disorders were used as controls for hepatic enzyme studies. Hepatic damage indicators (aspartate aminotransferase, AST; alanine aminotransferase, ALT; and bilirubin) correctly classified 86-96% of non-RS cases and 61-71% of RS. By contrast, AST and ALT had little prognostic value (63% overall correct). Ammonia effectively classified favorable outcome cases (95% correct) but not unfavorable (14% correct). However, when ammonia was included with stage of coma information 88% of the favorable and 85% of the unfavorable outcome cases were correctly classified. Discriminant analysis of hepatic enzymes (glutamate dehydrogenase and monoamine oxidase activity) for a RS and a non-RS group correctly classified 80% of non-RS and 95% of RS specimens. The function was suitable for the direct evaluation of RS-like mitochondrial enzyme changes in rat liver.
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PMID:Prognosis and diagnosis of Reye syndrome by discriminant analysis. 404 46

Following reports of a Reye-like syndrome in children resulting from Margosa oil (MO) ingestion, we administered MO to laboratory rats in an attempt to produce an animal model of Reye's syndrome. Male rats were injected intraperitoneally with either MO or corn oil and observed for clinical signs of a toxic response. After 15 h the animals were administered a second dose and the MO-treated animals developed florid neurological symptoms. The animals were then sacrificed and blood samples were analyzed for glucose, ammonia, aspartate aminotransferase, and alanine aminotransferase. Sections of liver, kidney, and brain were examined by light microscopy after Sudan black B, hematoxylin and eosin, and periodic acid-Schiff staining. Liver was additionally examined by electron microscopy. Liver samples were analyzed for hepatic enzyme levels and brain samples were analyzed for water content. There were greatly increased levels of ammonia, aspartate aminotransferase, and alanine aminotransferase and decreased glucose levels in the blood of MO-treated animals. Light microscopy of MO-treated livers revealed fatty infiltration, granularity of the cytoplasm with normal nuclei, and glycogen depletion; electron microscopy revealed mitochondrial pathology in the livers of MO-treated animals. There were no significant morphological changes in brain or kidney specimens although the kidneys did show some fatty infiltration. Hepatic mitochondrial enzyme levels were unchanged and there was no increase in brain water content in the MO-treated animals. Thus, many of the abnormalities seen in Reye's syndrome were seen in this model; however, there were no hepatic enzyme changes despite altered mitochondrial morphology and no evidence of cerebral edema despite a florid encephalopathy. Nonetheless, this model may have important implications for the understanding of the pathogenetic mechanisms of this Reye-like syndrome and, perhaps, Reye's syndrome.
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PMID:Investigation of an animal model of a Reye-like syndrome caused by Margosa oil. 408 Apr 57

In this study, we tested a new artificial liver device using liver pieces in 8-h hemoperfusion of comatous porcine blood and compared two alternative tissue preparations. Acute hepatic coma in the pigs was induced by complete devascularization of the liver. The animals were killed in stage IV coma (15-25 h after the operation), and 1 l blood was perfused over 200 g fresh or DMSO-preserved liver cubes. After the devascularization GOT, GPT, GLDH, AP, LDH, SDH, bilirubin, free fatty acid, and bile acid levels in serum increased progressively. Ammonia concentrations underwent a rapid increase in the first 9 h of coma development from 126.0 +/- 9.9 to 321.9 +/- 62.2 mumol/l. Most of the amino acids in serum were elevated and molar ratio of BCAA/AAA declined from 3.87 +/- 0.79 to 0.92 +/- 0.24. In the course of hemoperfusion ammonia was removed from the perfusate to 71% of the initial values using fresh and to 39% using preserved tissue. Correspondingly, there was an increase in urea concentrations. Amino acid metabolism was ameliorated during the perfusion; Fischer's quotient increased from 0.91 +/- 0.15 to 1.38 +/- 0.14 (fresh liver) and from 0.89 +/- 0.14 to 2.11 +/- 0.44 (preserved liver); neuroexcitatory amino acids Asp and Glu were markedly elevated. Energy charge of the liver cells increased and reached levels exceeding 0.5 in both experimental groups, a balanced energy metabolism was maintained and suggests active metabolization by the liver pieces. In comparison with fresh tissue, preserved liver cubes proved effective. We consider our artificial liver device capable of temporary hepatic support in acute necrosis of the liver and suppose that its efficiency can be potentiated by combining this system with other procedures.
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PMID:Successful treatment of hepatic coma by a new artificial liver device in the pig. 408 14

1. The time-course of the changes in the concentrations of hepatic metabolites in response to a non-toxic load of NH(4)Cl were measured in fed and starved rats. 2. There was a rapid increase (after 2min) in [alanine] and [aspartate] which remained high for 10-15min; the absolute increase in [alanine] was smaller in starved rats. 3. These changes were accompanied by a decrease in [oxoglutarate] and in the [3-hydroxybutyrate]/[acetoacetate] ratio. 4. Prior administration of l-arginine to fed rats resulted in smaller increases in [alanine] and [aspartate] after the ammonia load. This is presumably due to stimulation of the urea cycle. 5. Increased formation of alanine in starved rats occurred after prior administration of dihydroxyacetone to increase the availability of pyruvate. 6. Administration of l-cycloserine, an inhibitor of glutamate-alanine aminotransferase, completely prevented the increase in [alanine] after the ammonia load; in this case the absolute increase in [aspartate] was higher. 7. [Oxoglutarate], [citrate] and [isocitrate] at 25min after the ammonia load were higher than the initial concentrations, but returned to normal by 50min. It is suggested that this ;overshoot' may be due to temporary compartmentation of oxoglutarate. 8. The mechanisms and physiological significance of alanine and aspartate formation in these experiments are discussed.
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PMID:Mechanisms for the formation of alanine and aspartate on rat liver in vivo after administration of ammonium chloride. 415 44

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. The activities of gluconeogenic and glycolytic enzymes and the concentrations of citrate, ammonia, amino acids, glycogen, glucose 6-phosphate, acetyl-CoA, lactate and pyruvate were measured in kidney cortex of normal, diabetic, cortisone-treated and growth hormone-treated rats. 2. In kidney cortex of diabetic, cortisone-treated and growth hormone-treated rats the activities of glucose 6-phosphatase (EC 3.1.3.9), fructose 1,6-diphosphatase (EC 3.1.3.11) and phosphopyruvate carboxylase (EC 4.1.1.32) were increased. 3. The activities of glutamate dehydrogenase (EC 1.4.1.3), alanine aminotransferase (EC 2.6.1.2), aspartate aminotransferase (EC 2.6.1.10) and pyruvate carboxylase (EC 6.4.1.1) were increased in diabetic and cortisone-treated rats. In growth hormone-treated rats the activity of aspartate aminotransferase was depressed but those of the other three enzymes were unchanged. 4. The activity of hexokinase (EC 2.7.1.1) was not altered in any of these conditions. Phosphofructokinase (EC 2.7.1.11) activity was depressed only in growth hormone-treated rats. Pyruvate kinase (EC 2.7.1.40) activity was depressed in cortisone-treated and growth hormone-treated rats but unchanged in diabetic rats. 5. Amino acids, acetyl-CoA and glucose 6-phosphate contents were increased in rat kidneys in all these three conditions. Ammonia content was increased in diabetic and cortisone-treated rats but was markedly diminished in growth hormone-treated rats. 6. The [lactate]/[pyruvate] ratio was elevated in diabetic and cortisone-treated rats but unchanged in growth hormone-treated rats. Citrate content was increased in the kidney cortex of diabetic and growth hormone-treated rats but was unchanged in cortisone-treated rats. The activity of ATP citrate lyase (EC 4.1.3.8) was depressed in diabetic and growth hormone-treated rats but was increased in cortisone-treated rats. 7. Glycogen content was moderately elevated in growth hormone-treated rats and markedly elevated in diabetic rats, whereas no change in glycogen content was observed in cortisone-treated rats. Glycogen synthetase (EC 2.4.1.11) activity was unchanged in all these three conditions. Phosphorylase (EC 2.4.1.1) activity was not affected in cortisone-treated rats but was depressed in diabetic and growth hormone-treated rats.
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PMID:Evaluation of the rate-limiting steps in the pathway of glucose metabolism in kidney cortex of normal, diabetic, cortisone-treated and growth hormone-treated rats. 434 56

Aspartate transaminase, alanine transaminase, glutamate dehydrogenase, arginase, serine dehydratase, tyrosine transaminase, glutamine synthetase, glutaminase and adenylate deaminase activities were measured in crude homogenates of 12, 19 and 21-day rat placentae. There is a considerable quantitative importance in enzymes able to produce free ammonia, such as adenylate deaminase and glutamate dehydrogenase, activity that progressively decrease with the age of placenta. The glutamine synthetase and tyrosine transaminase activities increase with age, while serine dehydratase decreases considerably and aspartate and alanine transaminase do not change practically. Arginase shows a maximum at 19, with lower 12 and 21-day activities. No measurable glutaminase activity has been found. The possible implications of the enzymes studied upon the ammonia-producing activity of rat placenta are discussed together with the relative decreasing role of placenta for the overall metabolic activity of the foetus, especially during the last phases of its development.
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PMID:Activities of enzymes involved in amino-acid metabolism in developing rat placenta. 610 12

Evidence is provided for the utilization of glutamine by calvaria and compact bone of rat. Glutamine was actively transported into calvaria, principally by sodium-dependent mechanisms; its uptake was significantly inhibited by neutral amino acids (alanine, proline, serine, asparagine) and glutamine analogs (L-glutamate-gamma-hydroxamate, albizziin). Glutamine was degraded to ammonia and glutamate by phosphate-dependent glutaminase, a mitochondrial enzyme present in both calvaria and compact bone. The enzyme exhibited an apparent Kmgln of 2.35 mM, a KactPO4 of 25 mM, and a broad pH optimum (7.5-9.5). It was inactivated by incubation of intact calvaria or bone homogenates with the glutamine analogs 6-diazo-5-oxo-L-norleucine (DON) and a 2-amino-4-oxo-5-chloropentanoic acid (chloroketone). Such treatment also severely inhibited (greater than 95%) both ammonia and 14CO2 formation from [U-14C]glutamine. Glutamate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase activities were measured in bone. Amino-oxyacetate, an aminotransferase inhibitor, inhibited 14CO2 formation from [U-14C]glutamine. The data indicate that glutamine can serve as a precursor of ammonia, glutamate, other amino acids (alanine, aspartate, ornithine, proline) and carbon dioxide in bone and that phosphate-dependent glutaminase, transaminases, and citric acid cycle activity contribute to the observed metabolism.
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PMID:Glutamine metabolism in bone. 613 80

Metabolism of the glutamate group of amino acids--glutamic acid, gamma-amino-butyric acid, glutamine, aspartic acid and alanine--was studied in the brain of rat as a function of age. The levels of glutamic acid, glutamine and aspartic acid decreased while those of gamma-aminobutyric acid, and alanine increased with age. The results on the activity of the twelve enzymes involved in the metabolism showed that five of them (glutamate dehydrogenase, glutamine synthase, gamma-aminobutyric acid transaminase, succinic semialdehyde dehydrogenase and NAD+-isocitrate dehydrogenase) decreased, while four of them (glutaminase, glutamotransferase, glutamic acid decarboxylase, and alpha-ketoglutarate dehydrogenase) increased. The other three enzymes (aspartate aminotransferase, alanine aminotransferase and NADP+-isocitrate dehydrogenase) did not show any significant change in activity. An age-related increase was seen in alpha-ketoglutarate and ammonia, the intermediates involved in the metabolism of these amino acids. The changes in the level of these amino acids are discussed in relation to the altered energy metabolism during aging.
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PMID:Metabolism of the glutamate group of amino acids in rat brain as a function of age. 614 62


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