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)

The stabilities of nine rat liver cytosol enzymes were compared at a variety of pH values. The cytosol enzymes studied were (a) those with half-lives in vivo of 3 days or longer: lactate dehydrogenase, arginase, glyceraldehyde phosphate dehydrogenase and alanine aminotransferase, (b) those with half-lives in vivo shorter than 2 days; glucokinase, dihydroorotase, serine dehydratase and tyrosine aminotransferase and (c) catalase, which has an intermediate half-life of 2.5 days for the protein protion. All the enzymes were stable in vitro at neurtal and alkaline pH values. However, at acidic pH values (pH 4): the long-lived enzymes (a) were stable; the short-lived enzymes (b) were completely inactivated with one exception; and catalase was partially inactivated. Tyrosine aminotransferase was the exception in that it is a short-lived enzyme in vivo but stable under all conditions tested in vitro. The finding that long-lived enzymes are stable in an acid milieu and short-lived enzymes are generally unstable was only observed if certain ligands (NAD+, pyridoxal 5'-phosphate, Mn2+, amino acids) were added to the invitro system. Lysosomal extracts did not accelerate the rate of inactivation of any cytosol enzyme in acidic solutions. These results indicate that if degradation of intracellular enzymes occurs in lysosomes, acid inactivation and denaturation of enzymes may be the initial event in determining the functional half-lives of the enzymes in vivo.
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PMID:Acid inactivation of short-lived rat liver enzymes. 1 3

Regulation of the cytoplasmic enzymes, pyruvate kinase (PK), glucokinase (GK), phosphoenolpy ruvate carboxykinase (PEPCK), fructose-1,6-diphosphatase (FDP), ATP citrate-lyase (ATP-CL), NAD-malate dehydrogenase (NAD-MD), NADP-malate dehydrogenase (NADP-MD), glutamic-pyruvic transaminase (GPT), glucose-6-phosphate dehydrogenase (G6PD), and 6-phosphogluconate dehydrogenase (6PGD), in rat liver by dietary fat (F diet) and dietary sucrose (S diet) was investigated. Mealfeeding the S diet to adult rats for 5 and 9 months resulted in a diurnal dietary response (i.e., food response) variation of FDP, GK, ATP-CL, 6PGD, and PK, while meal-feeding the S diet to young rats resulted in diurnal dietary response variation of ATP-CL, G6PD, NADP-MD, 6PGD, GPT, and PK. Meal-feeding the fat diet results in essentially no diurnal variation in enzyme activity. The overall effect of meal-feeding, as compared with ad libitum feeding, of the S diet was to increase the levels of G6PD, ATP-CL, and NADP-MD and to decrease the level of PEck in the meal-fed rats. Young rats meal-fed the two diets have higher enzyme activities than meal-fed adult rats for the observed enzymes (except for GPT and NAD-MD). In general, hepatic levels of the enzymes studied are low in the F diet-fed animals and markedly higher for the S diet-fed animals. These results suggest that dietary carbohydrate specifically induces those enzymes involved in carbohydrate metabolism, whereas dietary fat does not affect their levels. On the basis of prior evidence for an early requirement of RNA synthesis for sucrose induction of G6PD, this widespread induction of liver enzymes by carbohydrate must indicate either increased synthesis of ribosomal RNA with later regulation of synthesis specifically of these enzymes or increased synthesis of a rather large group of specific messenger RNAs i.e., coordinate genetic control of a number of these enzyme messenger RNAs.
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PMID:Effect of dietary fat and sucrose on the activities of several rat hepatic enzymes and their diurnal response to a meal. 16 37

Twenty-four male (12 obese and 12 lean) and 21 female (11 obese and 10 lean) SHR/N-cp rats were fed a diet containing either 54% sucrose or starch for periods of 3-4 months. Rats were killed after a 14-16 h fast and liver enzyme activities were determined in both sex groups. Liver glucose-6-phosphatase (G6Pase), fructose 1,6-bisphosphatase (FBPase), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), malic enzyme (ME), phosphofructokinase (PFK), glucokinase (GK), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels (per total liver capacity) were significantly affected by phenotype (obese > lean). Arginase and ornithine transcarbamylase levels were analysed only in male rats and were found to be elevated in obese rats as compared to lean littermates. Some of the above changes in enzyme levels were exaggerated by sucrose feeding but not the changes in FBPase, PEPCK, ME and GK (in both sexes) plus AST, arginase and arginine synthase activities in male rats and ALT levels in female rats. Results from SHR/N-cp rats published in this paper were compared to results obtained from LA/N-cp rats published previously. Comparison of the non-diabetic obese LA/N-cp with the diabetic obese SHR/N-cp male shows a greater excess in lipogenic capacity of the liver in the LA/N-cp male rat. The SHR/N-cp obese female also shows a greater liver lipogenic capacity as compared with the obese male SHR/N-cp rat. The results suggest that an adaptation of excessive lipogenesis in the liver of obese rats may be an anti-diabetogenic adaptation resulting in increased glucose conversion to lipids, thus reducing blood glucose levels.
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PMID:Adaptation in enzyme (metabolic) pathways to obesity, carbohydrate diet and to the occurrence of NIDDM in male and female SHR/N-cp rats. 133 Sep 56

Twenty obese and 20 lean LA/N-cp male rats and 20 male Sprague-Dawley rats were fed a diet containing either 54 percent sucrose or starch for six weeks. After a 14-16 hour fast, rats were killed. Liver and kidney enzyme activities were determined in the LA/N-cp rats while plasma urea and selected amino acids were determined in all rats. Liver glucose-6-phosphatase (G6PASE), fructose-1,6-bisphosphatase (FBPASE), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), malic enzyme (ME), glucokinase (GK), pyruvate kinase (PK), phosphofructokinase (PFK), glutamic-oxaloacetic-transaminase (GOT), glutamic-pyruvic transaminase (GPT), arginase (ARGASE), arginine-synthase (ARG-SYN) and ornithine transcarbamylase (OTC) levels were significantly affected by phenotype (obese greater than lean). All the above changes in enzyme levels were exaggerated by sucrose-feeding with the exception of PK, PFK, GOT, GPT, ARGASE and ARG-SYN. Kidney cortex G6PASE, PEPCK and ARGASE activities were higher in the obese rats as compared to the lean littermates. Sucrose feeding resulted in higher cortex G6PASE, FBPASE and PEPCK as compared to starch-fed rats. A phenotype effect was noted with plasma glutamate, urea, leucine, isoleucine and valine (obese greater than lean) and a diet effect was seen with aspartate, phenylalanine, leucine and valine (sucrose greater than starch) concentration. Sprague-Dawley rats had higher plasma urea and lower alanine than lean LA/N-cp males. Metabolic obesity in the LA/N-cp rat appears to involve an elevated capacity for pathways of glycolysis, gluconeogensis, lipogenesis and amino acid catabolism in the liver.
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PMID:Effect of dietary carbohydrate on liver and kidney enzyme activities and plasma amino acids in the LA/N-cp rat. 204 12

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

Glycosomes and mitochondrial vesicles from cultured promastigotes of Leishmania mexicana mexicana have been separated using isopycnic centrifugation on linear sucrose gradients. Hexokinase (EC 2.7.1.2), glucose phosphate isomerase (EC 5.3.1.9), phosphofructokinase (EC 2.7.1.11), glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12), and phosphoenolpyruvate carboxykinase (EC 4.1.1.49) were recovered largely in association with glycosomes (density; 1.215 g/ml). Phosphoglycerate kinase (EC 2.7.2.3) and glucose-6-phosphate dehydrogenase (EC 1.1.1.49) had some small glycosomal activity, but were mostly recovered in the soluble fractions. Malate dehydrogenase (EC 1.1.1.37) showed a broad peak corresponding to that of the mitochondrial marker oligomycin-sensitive ATPase (EC 3.6.1.4) (density; 1.190 g/ml). Glutamate dehydrogenase (EC 1.4.1.3) and alanine aminotransferase (EC 2.6.1.2) both showed small mitochondrial peaks, but most of the activities were recovered elsewhere on the gradient and in the soluble fractions. The subcellular location of enzymes in L.m. mexicana amastigotes was investigated by following the release of soluble enzymes from digitonin-treated amastigotes. This revealed distinct cytosolic, mitochondrial, and glycosomal compartments. The findings give an insight into the organization and control of L.m. mexicana promastigote and amastigote energy metabolism.
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PMID:Leishmania mexicana: subcellular distribution of enzymes in amastigotes and promastigotes. 315 38

Enzymes in the histologically normal liver of hosts of mammary carcinomas were examined for their responsiveness to endocrine and dietary modulations. Treatments with the developmental stimuli of alanine aminotransferase (glucocorticoids) and of pyruvate kinase (thyroid hormone) which had no effect in control adult rats raised the levels of these enzymes in the tumor-bearing rats. The latter also showed a greater percentage of increase in malic enzyme upon thyroid hormone administration than did control animals. The tumor-induced increase in hexokinase remained unaltered by the various dietary treatments; enzymes at subnormal levels were raised (glucokinase, malic enzymes, and pyruvate kinase) or further decreased (alanine aminotransferase and ornithine aminotransferase) by excessive carbohydrate intake in immature and adult experimental rats. The normal upsurge of glucokinase and malic enzyme upon weaning to the standard solid diet (from the relatively low-carbohydrate-containing milk) was prevented by cancerous growth in the organism. Similarly, the standard diet, which reversed within 2 days the partial loss of these enzymes in normal adult rats fasted for 48 hr, had no restorative effect on the essentially complete loss of the glucokinase and the very low malic enzyme activity in the fasted tumor bearers. The results suggest that failure in the dietary adaptations of hepatic enzymes as well as diminutions of their basal levels contributes to the clinically observed abnormalities in the glucose metabolism of cancer subjects.
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PMID:Hormonal and dietary regulation of hepatic enzymes in tumor-bearing rats. 683 4

In response to extrahepatic neoplasms, ornithine aminotransferase, malic enzyme, alanine aminotransferase and glucokinase activity of the 'uninvolved' liver is diminished and that of hexokinase is increased. Comparison of rats at various times after the implantation of ascites tumor, mammary carcinoma, fibrosarcoma and Morris hepatomas indicate that the faster the growth rate of tumors, the earlier the onset of these hepatic changes. The results also show that, when the different tumors are the same size, the magnitude of the enzymic deviations in the liver is directly related to characteristic growth rate of the tumor lines. These and previous observations on other host tissues suggest that tumor-doubling time, which is a known factor in metastatic spread and survival, may also be a variable in the production of systemic agents through which neoplasms affect the metabolic state of the cancer host.
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PMID:Effect of tumors with different growth rates on enzymes in host liver. 687 35

The effects of a high fat diet (30% (w/w) corn oil) on chronic streptozotocin-diabetic rats were investigated at the whole body level and at the enzyme level. The diet caused significant decreases in the extent of polydipsia (66% decrease), polyphagia (49%), polyuria (67%) and glycosuria (70%). The activities of selected hepatic enzymes from the glycolytic, gluconeogenic, ureogenic and lipogenic clusters were determined. The fat diet caused significant decreases (range: 47 to 54%) in the activity of the ureogenic enzymes carbamyl phosphate synthetase, ornithine transcarbamylase and arginase; had no effect on the glycolytic enzymes glucokinase, hexokinase and pyruvate kinase; partially decreased the diabetes-induced elevated activities of the gluconeogenic enzymes phosphoenolpyruvate carboxykinase (63% decrease), serine dehydratase (90%), alanine aminotransferase (31%) and aspartate aminotransferase (65%), and partially reversed the activity of one lipogenic enzyme, ATP citrate lyase.
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PMID:The effects of a high fat diet on chronic streptozotocin-diabetic rats. 692 68

Islets were isolated by automatic digestion from non-diabetic cadaveric organ donors and from Type 2 (non-insulin-dependent) diabetic subjects. The activity of FAD-glycerophosphate dehydrogenase, but not that of either glutamate dehydrogenase, glutamate-oxalacetate transaminase or glutamate-pyruvate transaminase, was lower in Type 2 diabetic patients than control subjects. Hexokinase, glucokinase and glutamate decarboxylase activities were also measured in islets from control subjects. The utilization of D-[5-3H]glucose, oxidation of D-[6-14C]glucose and release of insulin evoked by D-glucose were all lower in Type 2 diabetic patients than control subjects. The secretory response to the combination of L-leucine and L-glutamine appeared less severely affected. Islets from Type 2 diabetic patients may thus display enzymatic, metabolic and secretory anomalies similar to those often observed in animal models of Type 2 diabetes, including a deficiency of beta-cell FAD-linked glycerophosphate dehydrogenase, the key enzyme of the glycerol phosphate shuttle.
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PMID:Enzymatic, metabolic and secretory patterns in human islets of type 2 (non-insulin-dependent) diabetic patients. 816 52


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