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)

Oral administration of L-triiodothyronine (L-T3) (0.015-1 mg/kg) for 30 days to mature rats or cynomolgus monkeys resulted in both species in a high mortality at 1 mg/kg (after 2 weeks of treatment) and a progressive loss in body weight. Dose-related elevations in plasma marker enzymes occurred, mainly after 1-2 weeks of treatment. The approximate no-effect dose for these changes was around 0.015-0.020 mg/kg for both rat and primate. The large elevations of leucine aminopeptidase (LAP) at 1 mg/kg L-T3 in monkey indicated hepatocellular toxicity although in the rat such large increases in alanine aminotransferase (ALT) and glutamate dehydrogenase (GLDH) were not seen. L-T3 also showed little toxicity to rat hepatocytes in vitro. High concentrations of L-T3 (7 x 10(-9) to 7 x 10(-7) M) had minimal effects on parameters of cell viability such as lactate dehydrogenase (LDH) leakage, chromium-51 release and [3H]leucine incorporation. Urinary enzymes in the rat showed a similar profile to those in plasma. Large rises in alkaline phosphatase (AKP) and N-acetyl glucosaminidase (NAG) at 1 mg/kg indicated possible proximal tubular damage although this was not supported histologically. Clinically, in both species L-T3 appeared more toxic to males than females but this was not supported histologically. The histological lesions observed were different in the 2 species. In the monkeys there was extensive lipid vacuolation of hepatocytes and changes in thyroid and adrenal cortex. In the rat there was fine, non-lipid vacuolation of hepatocytes and thyroid changes. In the rat, 2 previously unreported lesions were also noted. There were multinucleated cells in the renal distal tubular epithelium, and focal fibroplasia of serosal surfaces of abdominal viscera.
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PMID:Comparison of the toxicity of orally administered L-triiodothyronine (T3) in rat and cynomolgus monkey. 320 78

The integrated use of several energy sources allows high muscular power outputs to be sustained. Muscle glycogen provides the major fuel source for muscular exercise, but other fuels can provide alternative energy sources which allow for muscle glycogen-sparing and an increased potential for prolonged high metabolic rates. Blood-borne glucose, derived from liver glycogenolysis and glyconeogenesis, as well as intra-muscular lipids and plasma free fatty acids derived from adipose tissue provide the main energy alternatives to muscle glycogen. Several amino acids, including the essential amino acid leucine, are also used directly as oxidizable fuels during exercise. Depending on the duration and intensity of exercise and other factors such as glycogen stores and energy intake, amino acids can provide from a few to approximately 10% of the total energy for sustained exercise. Additionally, many amino acids can be converted to glutamate (via glutamate dehydrogenase) and then to alanine (via glutamate-pyruvate transaminase). Alanine, along with lactate and pyruvate, are recognized as the major gluconeogenic precursors. Via this mechanism, several amino acids play crucial roles in providing the carbon sources for maintaining blood glucose homeostasis during exercise and glycogen restitution during recovery. And finally, during exercise and recovery, amino acids likely play important anaplerotic functions sustaining the whole metabolic apparatus.
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PMID:Amino acid and protein metabolism during exercise and recovery. 331 14

Maximal activities of rat skeletal muscle mitochondrial citrate synthase (CS), malate dehydrogenase (MDH), and alanine aminotransferase (ALT), as well as several other mitochondrial enzymes involved in various metabolic functions were significantly suppressed after a single bout of acute or exhaustive treadmill running. This enzymatic "down regulation" was maintained 24 and 48 h post exhaustion, especially in the untrained rats. Neither muscle cytosolic nor hepatic enzymes exhibited down regulation after exercise. Proteolysis was increased with exercise as assessed by the clearance of [3H]leucine previously incorporated into the proteins of the rats. Decreased CS, MDH, and ALT activities correlated with a significant loss of mitochondrial total protein sulfhydryl (r = 0.67, 0.68, 0.59, respectively, P less than 0.001) in untrained rats and both CS and MDH could be partially restored by incubation with dithiothreitol. Endurance-tested untrained and trained rats had significantly higher glutathione peroxidase (GPX) activity in both muscle mitochondria and cytosol which correlated significantly with endurance time (r = 0.70 and 0.74, respectively). It is concluded that enzymatic down regulation is not caused by proteolysis alone; i.e., peroxides and oxygen free radicals produced in prolonged exercise may alter the intramitochondrial redox state by oxidizing free thiols that may be required at active sites of these enzymes. Training may enhance the ability of the muscle to resist the toxic oxygen species by increasing GPX activity.
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PMID:Enzymatic down regulation with exercise in rat skeletal muscle. 336 59

The presence, in chronic active hepatitis (CAH) patients, of an inflammatory infiltrate basically composed of T lymphocytes suggested the hypothesis that these lymphocytes could play a role in the pathogenesis of the disease. The aim of this study has been to characterize, in a group of carefully selected CAH patients, the liver-infiltrating T lymphocyte, utilizing commercial monoclonal antibody (anti-Leu 1, anti-Leu 2a, anti-Leu 3a) and 5/9 monoclonal antibody that recognizes a further lymphocyte subset within T4 cells. Our data show that both T4 positive subpopulation and T8 positive subpopulation are represented in the infiltrate in the same ratio; furthermore the distribution of 5/9 positive lymphocytes is prevalent where the infiltrate is mainly composed of T8 positive lymphocytes. Moreover, there is a positive correlation between 5/9 positive cells in the liver and GPT and the patients with high percentages of infiltrating 5/9 positive lymphocytes show a low T4/T8 ratio with respect to patients with low percentages of 5/9 positive cells. These data support the hypothesis that 5/9 positive lymphocytes may present an inducer role on cytotoxic cells.
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PMID:A possible cytotoxicity inducer role of 5/9 positive lymphocytes infiltrating the liver in CAH patients. 349 78

The antitumor activity of RA-700, a cyclic hexapeptide isolated from Rubia Cordifolia, was evaluated in comparison with deoxy-bouvardin and vincristine (VCR). As regards the proliferation of L1210 cultured cells, the cytotoxicity of RA-700 was similar to that of VCR but superior to that of deoxy-bouvardin. The IC50 value of RA-700 was 0.05 mcg/ml under our experimental conditions. RA-700 inhibited the incorporation of 14C-leucine at a concentration at which no effects were observed on the incorporation of 3H-thymidine and 3H-uridine in L1210 culture cells in vitro. The antitumor activity of RA-700 was similar to that of deoxy-bouvardin and VCR against P388 leukemia. Daily treatment with RA-700 at an optimal dose resulted in 118% ILS. As with deoxy-bouvardin and VCR, the therapeutic efficacy of RA-700 depends on the time schedule. RA-700 showed marginal activity against L1210 leukemia (50% ILS), similar to that of deoxy-bouvardin but inferior to that of VCR. RA-700 inhibited Lewis tumor growth in the early stage after tumor implantation, whereas deoxy-bouvardin and VCR did not. As regards toxicity, a slight reduction of peripheral WBC counts was observed with the drug, but no reduction of RBC and platelet counts. BUN, creatinine, GPT and GOT levels in plasma did not change with the administration of the drug.
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PMID:Antitumor activity and toxicity in mice of RA-700, a cyclic hexapeptide. 363 86

After surgical placement of end-to-side portacaval shunts (PCS), 4 adult mongrel dogs (11.8 to 18.2 kg) were fed purified diets and monitored for approximately 50 weeks for changes in body weight, neurologic status, and an array of clinically important biochemical variables. Two healthy dogs, fed the same diets and maintained in the same environment, were also observed (controls). Body weights were relatively stable over the period of observation. The branched-chain ratio ([valine] + [leucine] + [isoleucine]/[phenylalanine] + [tyrosine]), an index of the degree of change in plasma amino acid concentrations, was significantly lower in dogs with PCS than in controls. Despite this depression in branched-chain ratio, the principals (dogs with PCS) were essentially free of neurologic symptoms. Statistically significant decreases due to portacaval shunting were seen in the serum concentrations of glucose, calcium, urea nitrogen, creatinine, cholesterol, and albumin. Total protein, globulin, and triglyceride concentrations tended to be lower in the serum of principals than in serum of controls, but the differences were not statistically significant. Statistically significant increases due to portacaval shunting were seen in plasma concentrations of total conjugated bile acids and sulfobromophthalein retention. Concentrations of the following compounds tended to be higher in serum of principals than in serum of controls: phosphorus, chloride, uric acid, total bilirubin, lactate dehydrogenase, aspartate transaminase, alanine transaminase, and alkaline phosphatase. Liver biopsy at 7 months after operation showed mild-to-extensive atrophy of hepatocytes, mild-to-extensive fibrosis, and collapsed portal veins in all principals examined.
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PMID:Long-term biochemical and physiologic effects of surgically placed portacaval shunts in dogs. 395 18

Muscle branched-chain amino acid metabolism is coupled to alanine formation via branched-chain amino acid aminotransferase and alanine aminotransferase, but the subcellular distributions of these and other associated enzymes are uncertain. Recovery of branched-chain aminotransferase in the cytosol fraction after differential centrifugation was shown to be accompanied by leakage of mitochondrial-matrix marker enzymes. By using a differential fractional extraction procedure, most of the branched-chain aminotransferase activity in rat muscle was located in the mitochondrial compartment, whereas alanine aminotransferase was predominantly in the cytosolic compartment. Phosphoenolpyruvate carboxykinase, like aspartate aminotransferase, was approximately equally distributed between these subcellular compartments. This arrangement necessitates a transfer of branched-chain amino nitrogen and carbon from the mitochondria to the cytosol for alanine synthesis de novo to occur. In incubations of hemidiaphragms from 48 h-starved rats with 3mM-valine or 3mM-glutamate, the stimulation of alanine release was inhibited by 69% by 1 mM-aminomethoxybut-3-enoate, a selective inhibitor of aspartate aminotransferase. Leucine-stimulated alanine release was unaffected. These data implicate aspartate aminotransferase in the transfer of amino acid carbon and nitrogen from the mitochondria to the cytosol, and suggest that oxaloacetate, via phosphoenolpyruvate carboxykinase, can serve as an intermediate on the route of pyruvate formation for muscle alanine synthesis.
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PMID:Branched-chain amino acid metabolism and alanine formation in rat muscles in vitro. Mitochondrial-cytosolic interrelationships. 397 57

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

Statistical analysis of variance was applied to data from determinations of 14 plasma constituents in 25 rats in order to evaluate the analytical, experimental and biological (inter-and intraindividual) component of variance. Blood was taken seven times in intervals of 8-10 days, the last one by catheter technique and the other by heart puncture. The analytical portion of variance was determined by the concurrent analysis of a pool plasma standard. The experimental component of variance was evaluated by the comparison of the variation of the catheter values with that of the pooled data from heart puncture. The coefficient of variation for the latter may be grouped into three categories: less than 10% for protein, Na+, K+, Ca2+; 10-20% for urea, phosphate and the enzymes as alanine aminotransferase, choline esterase, alkaline phosphatase and leucine arylamidase and 20-65% for the other enzymes lactate dehydrogenase, malate dehydrogenase, aspartate aminotransferase and creatine kinase. The results from the samples taken by catheter technique generally revealed the lower values for the mean as well as for the variance. It became evident that the procedure of heart puncture is afflicted with the most aggravating interference factors, thus accounting for most of the experimental component of variance. The observed differences between the single blood drawings, the non-Gaussian distribution for several constituents, and the interactions between the components of variance do not always fit for the statistical concept of additivity of the single components.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biological, analytical and experimental components of variance in a long-term study of plasma constituents in rat. 660 70

Effects of cianidanol on chronic liver injury induced by prolonged administration of carbon tetrachloride (CCl4) and on liver regeneration after partial hepatectomy of normal liver and CCl4 chronically injured liver were investigated by the measurement of plasma and liver biochemical parameters. Cianidanol increased the total plasma protein and 14C-Leu incorporation into plasma protein, while it reduced the contents of liver cholesterol and triglycerides. In rats with chronically injured liver or regenerating liver after partial hepatectomy of chronically injured liver, cianidanol improved the retention rate of BSP and the content of liver sugar. In rats with chronically injured liver, plasma GPT and GOT activities were reduced with the administration of cianidanol. Cianidanol had no effect on the regeneration rate after partial hepatectomy of normal liver, but it increased the regeneration rate after partial hepatectomy of chronically injured liver. These results suggest that cianidanol has the effect of improving the function of liver cells damaged by CCl4 treatment and of promoting the recovery of cell function to a normal level.
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PMID:[Effects of cianidanol on chronic liver injury induced by carbon tetrachloride and on liver regeneration after partial hepatectomy in rats]. 661 44


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