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)

By paper chromatography, the tissue homogenate of Oncomelania snails was shown to form glutamic acid at the expense of alpha-ketoglutarate plus aspartic acid, alanine or arginine respectively. The existence of alanine-glutamate, aspartate-glutamate and arginine-glutamate transaminase in Oncomelania snail was demonstrated. By using colorimetric method, the activity of aspartate-glutamate transaminase (GOT) and alanine-glutamate transaminase (GPT) of Oncomelania snail was 1.64 +/- 0.01 and 0.99 +/- 0.01 mumol/h.mg protein respectively. GOT and GPT were not inhibited by 2 ppm bromoacetamide, but the activity of GPT was suppressed (40%) by 2 ppm nicotinanilide. A combination of 0.5 ppm bromoacetamide and 0.5 ppm nicotinanilide had no synergitic molluscicidal effect.
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PMID:[Preliminary studies on transaminase of Oncomelania snail]. 220 22

In order to clone hepatitis C (blood-borne non-A, non-B hepatitis) virus, lambda gt11-cDNA library was constructed from RNA extracted from 100 liters serum collected from 1,047 donors with elevated ALT levels and negative for hepatitis B virus-DNA. The library was immunoscreened on Y1090 cells with pooled serum obtained from patients with acute hepatitis C or chronic hepatitis C. By screening 29 clones specific for Japanese hepatitis C infection were isolated. The specificity of these clones for hepatitis C infection was determined by panels constructed in 3 laboratories. Of these, 12 clones were specific for American hepatitis C infection as well. The nucleotide sequence (201 bp) of one of them was determined to be unique compared to known human viruses including hepatitis A virus, hepatitis B virus and hepatitis D virus. Southern blot analysis showed the absence of the sequence of the human genome in the clone. The predicted amino acid sequence is rich in residues of lysine, arginine, glutamic acid and asparagine, while lacking leucine, cysteine and methionine.
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PMID:Cloning of a cDNA associated with acute and chronic hepatitis C infection generated from patients serum RNA. 250 78

The early stages of insulin-dependent diabetes mellitus are characterized by a selective inability to secrete insulin in response to glucose, coupled to a better response to nonnutrient secretagogues. The deficient glucose response may be a result of the autoimmune process directed toward the beta-cells. Interleukin-1 (IL-1) has been suggested to be one possible mediator of immunological damage of the beta-cells. In the present study we characterized the sensitivity of beta-cells to different secretagogues after human recombinant IL-1 beta (rIL-1 beta) exposure. Furthermore, experiments were performed to clarify the biochemical mechanisms behind the defective insulin response observed in these islets. Rat pancreatic islets were isolated and kept in tissue culture (medium RPMI-1640 plus 10% calf serum) for 5 days. The islets were subsequently exposed to 60 pM human recombinant IL-1 beta during 48 h in the same culture conditions as above and examined immediately after IL-1 exposure. The rIL-1 beta-treated islets showed a marked reduction of glucose-stimulated insulin release. Stimulation with arginine plus different glucose concentrations, and leucine plus glutamine partially counteracted the rIL-1 beta-induced reduction of insulin release. The activities of the glycolytic enzymes hexokinase, glucokinase, and glyceraldehyde 3-phosphate dehydrogenase, were similar in control and IL-1-exposed islets. Treatment with IL-1 also did not impair the activities of NADH+- and NADPH+-dependent glutamate dehydrogenase, glutamate-aspartate transaminase, glutamate-alanine transaminase, citrate synthase, and NAD+-linked isocitrate dehydrogenase. The oxidation of D-[6-14C]glucose and L-[U-14C]leucine were decreased by 50% in IL-1-treated islets. Furthermore, there was a significant decrease in the ratios of [2-14C]pyruvate oxidation/[1-14C]pyruvate decarboxylation and L-[U-14C]leucine oxidation/L-[1-14C]leucine decarboxylation, indicating that IL-1 decreases the proportion of generated acetyl-coenzyme-A residues undergoing oxidation. However, in the presence of IL-1 there was a significant increase in L-[U-14C]glutamate oxidation. These combined observations suggest that exposure to IL-1 induces a preferential decrease in glucose-mediated insulin release and mitochondrial glucose metabolism. This mitochondrial dysfunction seems to reflect an impairment in proximal steps of the Krebs cycle. It is conceivable that the IL-1-induced suppression and shift in islet metabolism can be an explanation for the beta-cell insensitivity to glucose observed in the early phases of human and experimental insulin-dependent diabetes mellitus.
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PMID:Differential sensitivity to beta-cell secretagogues in cultured rat pancreatic islets exposed to human interleukin-1 beta. 266 6

The prevalence of fatty liver disease at autopsy ranges from 40% to 80% in Europe and North America, and liver injury tests are abnormal in up to 8% of healthy populations. Liver injury tests were therefore examined in a group of 325 workers without exposure to hepatotoxins to identify the influence of obesity and gender. Obesity was a strong predictor of the degree of abnormality for serum levels of arginine and alanine aminotransferase and of alkaline phosphatase, even in the normal range. Women generally demonstrated lower levels of these enzymes. Workers with morbid obesity were substantially more likely to have abnormal liver injury tests. Obesity and gender must be considered in the interpretation of abnormal liver injury tests in hazardous waste workers.
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PMID:Liver injury tests in hazardous waste workers: the role of obesity. 291 8

A survey of aminotransferase activities present in a cell-free extract of the anaerobic protozoan, Trichomonas vaginalis was performed. 2-Oxoglutarate, oxaloacetate or phenylpyruvate acted as effective amino acceptors with tyrosine, phenylalanine, tryptophan, leucine, valine, isoleucine, aspartate, alanine, ornithine or lysine. Arginine, serine, glutamine, glycine, beta-alanine and gamma-aminobutyrate were not active as amino donors. With pyruvate as acceptor, significant, yet low, activity was seen only with glutamate, lysine or phenylalanine. Partial purification of enzymes catalysing transamination of leucine, valine, isoleucine, alanine, ornithine and lysine were carried out. A single enzyme catalysed the transamination of ornithine and lysine. The substrate specificity of this enzyme is novel. A separate enzyme catalysed the transamination of all three branched chain amino acids. A third enzyme catalysed the alanine aminotransferase reaction. A fourth enzyme catalysing the transamination both of aromatic amino acids and aspartate has previously been purified [Lowe, P.N. and Rowe, A.F. (1985) Biochem. J. 232, 689-695].
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PMID:Aminotransferase activities in Trichomonas vaginalis. 309 39

With respect to liver disease, the primary function of the laboratory is to identify its presence. Tests are not available that permit a specific diagnosis and an accurate prognosis. Several tests should be present in a minimum data base that can help identify hepatobiliary disease. They are ALT, SAP, total serum bilirubin, urine bilirubin, cholesterol, albumin, BUN, glucose, red cell morphology, and urine sediment. It is sometimes possible to tentatively identify whether a disease is primarily hepatocellular or biliary from the pattern of changes that occur in these tests. In addition, an estimate of the severity is sometimes possible when abnormal values are extreme. The keys are to avoid overinterpretation, use serial evaluations, and rely on a liver biopsy when definitive answers are needed. If liver disease is suspected but there are only marginal changes in the routine tests, the more sensitive tests of function, BSP retention and ammonia tolerance, are warranted. In the future, as more knowledge is gained about the responses of ARG, GGT, and ICG retention to naturally occurring diseases, these tests may join or replace some of those currently used. Also, as the ability to accurately and economically measure the various bile acids improves, a sensitive, yet noninvasive, method to detect and define modest changes in hepatobiliary function may result.
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PMID:Laboratory evaluation of liver disease. 387 5

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. Amino acid metabolism and protein synthesis in a Staphylococcus aureus mutant strain that requires pyrithiamine for optimum growth were studied and compared with those in the thiamine-requiring parent S. aureus. 2. The mutant strain utilized amino acids at a higher rate than did the parent strain. The utilization of glutamic acid, serine and glycine was much stimulated in the mutant strain. 3. The rate of oxidation of glutamic acid, aspartic acid, isoleucine and glycine was higher in the mutant strain. 4. The mutant strain contained serine, glycine, tyrosine, glutamic acid, aspartic acid, arginine and histidine as free amino acids, whereas the parent strain possessed lysine, arginine, histidine, aspartic acid and glutamic acid. 5. The mutant strain possessed slightly higher glutamate-oxalo-acetate transaminase activity, whereas the activities of glutamate-pyruvate transaminase were similar in both strains. 6. The incorporation of (14)C from [2-(14)C]-acetate into individual amino acids of the cell protein was greater in the mutant strain. 7. The incorporation of (14)C-labelled amino acids into the cell proteins of the mutant strain was not much different from that in the parent strain. 8. Induction of beta-d-galactosidase in the mutant strain did not occur, whereas induction of this enzyme is possible in the parent strain. Thiamine or pyrithiamine has no direct effect on the induction of beta-d-galactosidase.
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PMID:Amino acid metabolism and protein synthesis in a pyrithiamine-requiring Staphylococcus aureus mutant. 604 29

Some experimental and clinical studies were done from the metabolic viewpoint to elucidate the characteristics of myonephropathic-metabolic syndrome. In experimental dogs with their femoral arteries ligated and two third of femoral muscles divided, aldolase and myoglobin showed remarkable increase without significant changes in electrolytes. Slight increase of GPT and GOT was observed. Amino acids showed elevation in urea, taurin, leucin, isoleucin, valine, threonine, 3-methylhistidine, phenylalanine, histidine, lysine, methionine, tyrosine and anserin and decrease in glutamine, alanine, glycine, proline, carnosine, citrullin and arginine. In patients with acute arterial occlusion, potassium, GOT, LDH, CPK, lactate and pyruvate increased moderately and myoglobin showed remarkable increase and aldolase slight increase. Amino acids showed remarkable increase in 3-methylhistidine and beta-amino-isobutyric acid and moderate increase in phenylalanine and arginine. These results revealed that measurement of free amino acid concentration, especially that of methylhistidine as well as myoglobin, pyruvate, lactate and some other enzymes might be of great help to predict the prognosis of patients with acute arterial occlusion of the extremities.
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PMID:[Metabolic study on acute arterial occlusion of the extremities]. 667 89

Primary cultures of hepatocytes from postnatal Sprague-Dawley rats were grown in arginine-deficient, ornithine-supplemented medium to inhibit fibroblastic overgrowth and to selectively isolate relatively pure cultures of parenchymal hepatocytes. This system of primary cultures of rat hepatocytes was utilized to evaluate the cytotoxicity of certain tricyclic antidepressant drugs (TCAs). The compounds tested were chosen to represent two distinct chemical classifications of TCAs: the dibenzazepine derivatives, imipramine (1) and desipramine (D), and the dibenzocycloheptadiene derivatives, amitriptyline (A) and nortriptyline (N). The study also allowed direct comparison of the parent tertiary amines, A and I, and their respective demethylated pharmacologically active metabolites, N and D. The hepatotoxicity of the compounds was determined by measuring leakage of cytoplasmic enzymes, lactate dehydrogenase (LDH) and glutamic-pyruvic transaminase (GPT), into the culture medium and by assessing cell viability by the trypan blue dye exclusion test. LDH leakage was a more sensitive index of early cellular injury in this study. The compounds demonstrated a dose- and time-dependent order of toxicity; their hepatotoxicity potency was ranked as A = N greater than D greater than I.
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PMID:Evaluation of the cytotoxicity of tricyclic antidepressants in primary cultures of rat hepatocytes. 726


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