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)

The present investigation revealed the effect of the organochlorine insecticide dieldrin at the dose level 0.25 LD50 at different time intervals on the concentration of 11 rat brain amino acids, on the activities of glutamic oxyacetic transaminase (GOT), glutamic pyruvic transaminase (GpT) and cholinesterase. The study was also extended to include the total protein content during the tested periods. The daily injection of dieldrin caused a marked decrease in the levels of glutamic acid, glutamine and taurine and an increase in the levels of aspartic acid, asparagine, GABA, glycine, lysine, serine, alanine and histidine. However, the maximal increase and decrease were recorded for most of the tested amino acids at the end of the tested period. The activity of the transaminases increased significantly. The recorded values of GOT were usually higher than GPT. Cholinesterase activity was inhibited thoroughly during all the experimental periods. Total protein content was decreased in the experiment; the minimal value was given 3 days after the injection.
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PMID:Effect of dieldrin injection on the level of certain amino acids and some enzymes in rat brain. 287 4

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

Mice poisoned with acetaminophen were treated with esterase inhibitors, buthionine sulfoximine, and N-acetyl-L-lysine in experiments designed to explore the mechanism of N-acetylcysteine protection in vivo. Three esterase inhibitors, phenylmethylsulfonyl fluoride, bis-(p-nitrophenyl)-phosphate, and diisopropylfluorophosphate, had no effect on the antidote effectiveness of N-acetylcysteine, although each provided partial protection against acetaminophen poisoning. Buthionine sulfoximine, a specific inhibitor of gamma-glutamyl cysteine synthetase, antagonized the antidote effect of N-acetylcysteine. Acetaminophen-induced hepatotoxicity, as measured by plasma alanine aminotransferase activity, and mortality failed to decline, consistent with stimulation of glutathione synthesis as the primary mechanism of antidote protection. N-Acetyl-L-lysine was given at doses up to ten-fold higher than N-acetylcysteine yet had no effect on acetaminophen hepatotoxicity or its prevention by N-acetylcysteine. These results advance the view that N-acetylcysteine acts primarily as a glutathione precursor. They further suggest the esterase inhibitors limit poisoning by acetaminophen and may be useful agents in antagonizing the toxicity of other metabolically activated drugs.
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PMID:Effects of esterase inhibitors and buthionine sulfoximine on the prevention of acetaminophen hepatotoxicity by N-acetylcysteine. 310 95

A highly purified plasminogen concentrate, LYS-PLASMINOGEN Steam Treated, has been developed for thrombolytic therapy of arterial and venous occlusions in combination with fibrinolytic agents. In search of a highly efficient drug covering this indication, we decided to select the lys-form of plasminogen because of its higher affinity to fibrin in contrast to the glu-form. This property of lys-plasminogen also led us to expect an improved thrombolytic activity as opposed to other forms of the proenzyme. The intermediate product is manufactured from pooled human citrated plasma by ethanol fractionation after separation of coagulation factor proteins. Further processing includes specific transformation and purification steps. The final product is a freeze-dried preparation characterized by a high specific activity greater than or equal to 18.0 CU/mg protein and a content of lys-plasminogen of greater than or equal to 95%. To reduce the risk of viral infections, the plasma pool includes only plasma donations which are ALT tested and negative for HBsAg and anti-HIV. In addition the intermediate freeze-dried bulk powder is subjected to a virus inactivation procedure based on steam treatment for 10 hours under standardized product specific conditions without using special protein stabilizers. Physical parameters of steam treatment provide for a maximum virus killing effect without impairing the biological plasminogen activity or changing the molecular integrity of the product. In a preclinical test HIV was inactivated by 6 log 10 after 3 hours of steam treatment leaving a 7 hour safety margin for inactivation of more heat resistant viruses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Production and quality assurance of Lys-plasminogen steam treated. 312 8

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

The effect of a single oral dose of endosulfan (5 mg/kg body weight) on the uptake of certain nutrients and brush-border enzymes has been studied in rat intestine. The uptake of glucose and alanine was elevated but that of leucine was decreased in endosulfan-fed rats. There was no change in the uptake of phenylalanine and lysine in insecticide-fed rats. The activities of brush-border sucrase and alkaline phosphatase were considerably increased while the activity of Na+ K+ ATPase was reduced in endosulfan-exposed animals. The leucine aminopeptidase activity was unaffected in pesticide-treated rats. There was a significant decrease in cellular LDH and GOT activities with no change in GPT activity. Neither was there a considerable increase in the cellular glucose-6-phosphatase activity (P less than 0.01) in the pesticide-fed rats. These results suggest that endosulfan toxicity induces certain functional changes in the intestine.
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PMID:Effect of a single oral dose of endosulfan on intestinal uptake of nutrients and on brush-border enzymes in rats. 618 May 24

Experiments were conducted with intact rat hepatocytes to identify inhibitors and incubation conditions that cause selective inhibition of alanine aminotransferase or aspartate aminotransferase. Satisfactory results were obtained by preincubating cells with L-cycloserine or L-2-amino-4-methoxy-trans-but-3-enoic acid in the absence of added substrates. When cells were incubated for 20 min with 50 microM-L-cycloserine, alanine aminotransferase activity was decreased by 90%, whereas aspartate aminotransferase was inhibited by 10% or less. On subsequent incubation, synthesis of glucose and urea from alanine was strongly inhibited, but glucose synthesis from lactate was unaffected. L-2-Amino-4-methoxy-trans-but-3-enoic acid (400 microM) in hepatocyte incubations caused 90-95% inactivation of aspartate aminotransferase, but only 15-30% loss of alanine aminotransferase activity. After preincubation with the inhibitor, glucose synthesis from lactate was almost completely blocked; with alanine as the substrate, gluconeogenesis was unaffected, and urea synthesis was only slightly decreased. By comparison with preincubation with inhibitors, simultaneous addition of substrates (alanine; lactate plus lysine) and inhibitors (cycloserine; aminomethoxybutenoic acid) resulted in smaller decreases in aminotransferase activities and in metabolic rates. Other compounds were less satisfactory as selective inhibitors. Ethylhydrazinoacetate inactivated the two aminotransferases to similar extents. Vinylglycine was almost equally effective in blocking the two enzymes in vitro, but was a very weak inhibitor when used with intact cells. Concentrations of DL-propargylglycine (4 mM) required to cause at least 90% inhibition of alanine aminotransferase in hepatocytes also caused a 16% decrease in aspartate aminotransferase. When tested in vitro, alanine aminotransferase was, as previously reported by others, more sensitive to inhibition by amino-oxyacetate than was aspartate aminotransferase, but in liver cell incubations the latter enzyme was more rapidly inactivated by amino-oxyacetate.
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PMID:Selective inhibition of alanine aminotransferase and aspartate aminotransferase in rat hepatocytes. 646 97

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

Four trials involving 192 Large White X Landrace pigs were conducted to investigate the effect of wide variation of dietary methionine, lysine and caloric density on the activity of hepatic glutamate-oxalate ad glutamate-pyruvate transaminases. Results of the study show that: The activities of the two transaminases were influenced by the nutritional treatments. GOT and GPT activity exhibited significant positive and negative quadratic relationship respectively with dietary methionine levels. Both GOT and GPT activities decreased with increasing caloric density or palm oil level of the diet. In weanling pigs, both GOT and GPT exhibited significant negative quadratic relationship with dietary lysine levels and were also significantly influenced by the sex of the animals. In older pigs, only GOT activity was significantly affected by dietary lysine levels. The correlation of GOT and GPT activities to dietary essential amino acids shows that hepatic enzymatic activities could be good indices of essential amino acid utilization.
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PMID:Liver glutamate-oxalate transaminase and glutamate-pyruvate transaminase activity in pigs as influenced by dietary methionine and lysine levels. 678 54

It has been shown that the circulating antibodies, which bind to rat hepatic microsomal proteins obtained after in vivo exposure to halothane, are detectable by immunoblotting in patients with "halothane hepatitis (HH)," and that rabbit immunized anti-sera against trifluoroacetylated rabbit serum albumin (TFA-RSA) recognizes rat microsomal distorted polypeptides in almost the same way as do sera from patients with HH. In this paper, we report first the development of a novel method of synthesizing TFA-RSA using p-nitrophenyl TFA, and second the results of tests for circulating anti-TFA antibodies in the serum of 86 patients who had received halothane anaesthesia and developed no (67 patients) or mild (19 patients, the maximum activity of serum alanine aminotransaminase 519 IU.L-1) liver damage. Serum was selected from stored sera of post-transfusion patients. The new method of synthesizing TFA-RSA was convenient and was able to be done at neutral pH. Rabbit sera obtained after immunization with the newly synthesized TFA-RSA recognized the same polypeptides (109 kDa, 92 kDa, 80 kDa, 76 kDa, 64 kDa and 59 kDa) as the established anti-sera against TFA-RSA, and these reactions were inhibited in the presence of TFA-lysine. Circulating antibodies were not detected in our patients who had developed no or mild liver damage. The present finding supports the hypothesis that the appearance of circulating antibodies against microsomal distorted proteins are specific to patients with HH. Furthermore, we have shown here that the halothane-induced mild increase in ALT activity is not associated with the appearance of those circulating antibodies, supporting the pathophysiological difference between HH and halothane-induced mild hepatic damage.
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PMID:Absence of anti-trifluoroacetate antibody after halothane anaesthesia in patients exhibiting no or mild liver damage. 805 7


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