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:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leucine and monomethyl succinate initiate insulin release, and glutamine potentiates leucine-induced insulin release. Alanine enhances and malate inhibits leucine plus glutamine-induced insulin release. The insulinotropic effect of leucine is at least in part secondary to its ability to activate glutamate oxidation by glutamate dehydrogenase (Sener, A., Malaisse-Lagae, F., and Malaisse, W. J. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 5460-5464). The effect of these other amino acids or Krebs cycle intermediates on insulin release also correlates with their effects on glutamate dehydrogenase and their ability to regulate inhibition of this enzyme by alpha-ketoglutarate. For example, glutamine enhances insulin release and islet glutamate dehydrogenase activity only in the presence of leucine. This could be because leucine, especially in the presence of alpha-ketoglutarate, increases the Km of glutamate and converts alpha-ketoglutarate from a noncompetitive to a competitive inhibitor of glutamate. Thus, in the presence of leucine, this enzyme is more responsive to high levels of glutamate and less responsive to inhibition by alpha-ketoglutarate. Malate could decrease and alanine could increase insulin release because malate increases the generation of alpha-ketoglutarate in islet mitochondria via the combined malate dehydrogenase-aspartate aminotransferase reaction, and alanine could decrease the level of alpha-ketoglutarate via the alanine transaminase reaction. Monomethyl succinate alone is as stimulatory of insulin release as leucine alone, and glutamine enhances the action of both. Succinyl coenzyme A, leucine, and GTP are all bound in the same region on glutamate dehydrogenase, where GTP is a potent inhibitor and succinyl coenzyme A and leucine are comparable activators. Thus, the insulinotropic properties of monomethyl succinate could result from it increasing the level of succinyl coenzyme A and decreasing the level of GTP via the succinate thiokinase reaction.
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PMID:Regulation of insulin release by factors that also modify glutamate dehydrogenase. 304 28

The pharmacokinetics of 125I-labelled Androctonus amoreuxi venom and its lethal fraction was studied in rabbits. Comparative pharmacokinetic studies of labelled A. amoreuxi, Leisurus quinquestriatus and Buthotus judaicus venoms were carried out in guinea-pigs. The pharmacokinetics of A. amoreuxi venom was also studied in rats. Groups of rats were injected with labelled A. amoreuxi venom and killed at frequent time intervals for the determination of the relative tissue venom concentration as a function of time. Several groups of rabbits were injected with A. amoreuxi venom and serial blood samples withdrawn at time intervals comparable with those used in the pharmacokinetic studies for the determination of serum glucose, insulin, cortisol, total proteins, albumin, globulins, cholesterol, total bilirubin, urea, uric acid, bicarbonate, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, sodium, potassium, calcium and phosphorus. The packed cell volume, and total and differential leucocyte counts were also determined. In another series of experiments continuous monitoring of the electrocardiograms of rabbits following venom injection was made to correlate any abnormalities with tissue venom concentration. All three venoms and the lethal fraction showed an open two-compartment behaviour with rapid distribution half-lives ranging between 4 and 7 min and overall elimination half-lives of 4.2 to 13.4 hr. The behaviour of A. amoreuxi venom was not markedly different in the three species of animals used. In a given species (guinea-pigs) the behaviour of the three venoms was not markedly different. Correlation of the ECG changes with cardiac venom concentration showed that arrhythmias and infarction occurred at times when cardiac concentration was very low, indicating that the cardiac abnormalities might result from indirect factors. Comparison of the course of the biochemical changes with venom concentration in the central compartment indicated that the site of action of the venom is not located in the central compartment. Correlation of the intensity of the biochemical effects with venom concentration in the peripheral compartment revealed an apparent delay in the onset and peak of action. This was explained by assuming that the tissue compartment could be divided into a rapidly accessible and a slowly accessible compartment with the venom acting through the slowly accessible compartment. There was also the possibility of the venom acting indirectly through the release of other substances or transformation to an intermediate.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Are the toxicological effects of scorpion envenomation related to tissue venom concentration? 329 64

A randomized, single-blind controlled multicenter study of insulin and glucagon infusion was carried out in 66 patients with acute alcoholic hepatitis. Thirty-three patients were treated with insulin 10 U and glucagon 1 mg in 500 ml 5% glucose in water via a peripheral vein for 2-6 h three times every day for 3 weeks. Patients in the control group received 5% glucose in an identical fashion. Fourteen control patients and five treated patients died from liver failure during the study (P less than 0.02). Clinical features of liver disease on entry into the study were similar in the two groups, but the total serum bilirubin, aspartate aminotransferase, gamma-glutamyltranspeptidase activities and prothrombin time significantly improved in the treated patients (P less than 0.05). Insulin and glucagon infusion appears to be a promising treatment of acute alcoholic hepatitis.
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PMID:A prospective multicenter study of insulin and glucagon infusion therapy in acute alcoholic hepatitis. 332 Jan 81

Serum concentrations of total proteins, albumin, glucose, alkaline phosphatase, alanine transaminase, aspartate transaminase, gamma-glutamyltransferase, lactate dehydrogenase, creatine kinase, urea, creatinine, total calcium, ionised calcium, total magnesium, sodium chloride, potassium, phosphorus, cortisol, parathormone, 25-hydroxy-VitD3 and insulin as well as the results of haematological investigations in Cape vultures (n = 10) are presented.
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PMID:Serum biochemical and haematological parameters in the Cape vulture Gyps coprotheres. 350 9

The streptozotocin diabetic rat was selected as a model to study how insulin deficiency alters vitamin B6 utilization by focusing on pyridoxal phosphate levels and aspartate aminotransferase activities in liver tissues. Diabetes of 15 weeks' duration lowered plasma pyridoxal phosphate levels by 84%. Normal plasma pyridoxal phosphate was 480 pmole/ml. Fractionation of liver into mitochondrial and extramitochondrial compartments demonstrated that diabetes caused a 43% diminution in mitochondrial pyridoxal phosphate per gram of liver. There was no cytoplasmic change in these diabetic rats. Mitochondrial aspartate aminotransferase activity was decreased 53% per gram of diabetic liver and cytoplasmic aspartate aminotransferase activity was elevated 3.4-fold. Damage to diabetic mitochondria during preparation procedures could not account for the rise in cytoplasmic aspartate aminotransferase activity. Electrophoresis showed that in the diabetic cytoplasm both cathodal and anodal forms of the enzyme were elevated. Speculations concerning mitochondrial loss and cytoplasmic gain of enzyme activity as well as those on the reduction of plasma pyridoxal phosphate in the diabetic rat are presented.
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PMID:Experimental diabetes causes mitochondrial loss and cytoplasmic enrichment of pyridoxal phosphate and aspartate aminotransferase activity. 374 6

Biological intra-individual variation in concentrations of 16 clinical biochemical analytes in serum was estimated for 27 patients with insulin-dependent diabetes mellitus (IDDM), and results were compared with those for apparently healthy individuals. In general, the variation was significantly higher in the patients. The ratio of the average intra-individual variation in IDDM patients to that in normal subjects exceeded 2.0 for Na+, K+, creatinine, and alpha-amylase; 1.50 to 2.0 for Cl-, total protein, albumin, cholesterol, and hemoglobin; and 1.2 to 1.5 for urea, uric acid, high-density-lipoprotein cholesterol, and aspartate aminotransferase. This increased variability in IDDM patients may be caused by variations in osmotic diuresis. Average intra-individual variations were greater for women than for men for Na+, total protein, albumin, and hemoglobin. Individual values showed a gaussian distribution for all analytes, including enzymes and triglycerides. No intra-individual variation was time dependent. For practical purposes, decision-making criteria in monitoring IDDM can be derived from the estimated biological component of intra-individual variation and the analytical variation established for each laboratory.
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PMID:Intra-individual variation of some analytes in serum of patients with insulin-dependent diabetes mellitus. 380 96

Cytoplasmic proteins are degraded with different half-lives in vivo. Large parts of proteins are believed to be degraded primarily in autophagic vacuoles-lysosomal system. However, the mechanism by which cell proteins are delivered to lysosomes and whether such a process might be selective for certain cell proteins are still unresolved. We examined the mechanism of autophagy with isolated autophagic vacuoles. Administration of leupeptin, a inhibitor of lysosomal thiol proteinases, induced the accumulation of numerous autophagic vacuoles in the liver. Highly purified preparation of autophagic vacuoles was isolated by Percoll density gradient equilibrium fractionation of crude lysosomal fractions. When cytosolic enzyme activities in autophagic vacuoles were measured, tyrosine aminotransferase and tryptophan oxygenase with short half-lives, and lactic dehydrogenase and aspartate aminotransferase with long half-lives were detected at similar ratios of enzymes in autophagic vacuoles/cytosol. During the time that cathepsin B plus L activities in autophagic vacuoles are inhibited by the injection of leupeptin, cytosolic enzymes are being accumulated in autophagic vacuoles suggesting that leupeptin blocks intralysosomal proteolysis, and that cytosolic enzymes are sequestered continuously into autophagosomes. Administration of glucocorticoid, which induces the synthesis of tyrosine aminotransferase, tryptophan oxygenase and cytosolic aspartate aminotransferase, selectively increased the sequestration of these enzymes to proportional degrees. Dietary manipulation and administration of insulin, which inhibit the formation of autophagic vacuoles, suppressed completely the accumulation of autophagic vacuoles in liver by administration of leupeptin. Results indicate that there is no selective uptake of cytosolic enzymes into autophagosome. When distribution of lysosomal cathepsin B and L in liver, which are inhibited strongly by leupeptin, was examined immunohistochemically, cathepsin L is found only in hepatocytes, but cathepsin B is localized in sinusoidal cells rather than in hepatocytes, suggesting that cathepsin L plays a most important role in intralysosomal proteolysis in hepatocytes.
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PMID:Lysosomal sequestration of cytosolic enzymes and lysosomal thiol cathepsins. 390 2

Regionally selective and time-dependent variations were observed in the activity of brain aspartate aminotransferase at early phases of diabetes. Malate dehydrogenase activity showed an opposite pattern of changes in soluble and particulate fractions of cerebral hemispheres and brain stem, with cerebellum showing consistent increase in the activity. The activity of both the enzymes increased significantly in liver, in contrast to heart where malate dehydrogenase activity decreased in particulate fraction. Insulin treatment to diabetic animals restored the enzymes to near control levels at early stages of diabetes, except in liver. The results indicate that malate-aspartate shuttle is probably stimulated under diabetic conditions to enable glycolysis to continue and ATP levels to be restored partially, particularly in cerebellum and liver.
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PMID:Malate-aspartate shuttle enzymes in rat brain regions, liver and heart during alloxan diabetes and insulin replacement. 391 Apr 26

1. A method is described for extracting separately mitochondrial and extramitochondrial enzymes from fat-cells prepared by collagenase digestion from rat epididymal fat-pads. The following distribution of enzymes has been observed (with the total activities of the enzymes as units/mg of fat-cell DNA at 25 degrees C given in parenthesis). Exclusively mitochondrial enzymes: glutamate dehydrogenase (1.8), NAD-isocitrate dehydrogenase (0.5), citrate synthase (5.2), pyruvate carboxylase (3.0); exclusively extramitochondrial enzymes: glucose 6-phosphate dehydrogenase (5.8), 6-phosphogluconate dehydrogenase (5.2), NADP-malate dehydrogenase (11.0), ATP-citrate lyase (5.1); enzymes present in both mitochondrial and extramitochondrial compartments: NADP-isocitrate dehydrogenase (3.7), NAD-malate dehydrogenase (330), aconitate hydratase (1.1), carnitine acetyltransferase (0.4), acetyl-CoA synthetase (1.0), aspartate aminotransferase (1.7), alanine aminotransferase (6.1). The mean DNA content of eight preparations of fat-cells was 109mug/g dry weight of cells. 2. Mitochondria showing respiratory control ratios of 3-6 with pyruvate, about 3 with succinate and P/O ratios of approaching 3 and 2 respectively have been isolated from fat-cells. From studies of rates of oxygen uptake and of swelling in iso-osmotic solutions of ammonium salts, it is concluded that fat-cell mitochondria are permeable to the monocarboxylic acids, pyruvate and acetate; that in the presence of phosphate they are permeable to malate and succinate and to a lesser extent oxaloacetate but not fumarate; and that in the presence of both malate and phosphate they are permeable to citrate, isocitrate and 2-oxoglutarate. In addition, isolated fat-cell mitochondria have been found to oxidize acetyl l-carnitine and, slowly, l-glycerol 3-phosphate. 3. It is concluded that the major means of transport of acetyl units into the cytoplasm for fatty acid synthesis is as citrate. Extensive transport as glutamate, 2-oxoglutarate and isocitrate, as acetate and as acetyl l-carnitine appears to be ruled out by the low activities of mitochondrial aconitate hydratase, mitochondrial acetyl-CoA hydrolyase and carnitine acetyltransferase respectively. Pathways whereby oxaloacetate generated in the cytoplasm during fatty acid synthesis by ATP-citrate lyase may be returned to mitochondria for further citrate synthesis are discussed. 4. It is also concluded that fat-cells contain pathways that will allow the excess of reducing power formed in the cytoplasm when adipose tissue is incubated in glucose and insulin to be transferred to mitochondria as l-glycerol 3-phosphate or malate. When adipose tissue is incubated in pyruvate alone, reducing power for fatty acid, l-glycerol 3-phosphate and lactate formation may be transferred to the cytoplasm as citrate and malate.
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PMID:The intracellular localization of enzymes in white-adipose-tissue fat-cells and permeability properties of fat-cell mitochondria. Transfer of acetyl units and reducing power between mitochondria and cytoplasm. 439 82

16 patients with carcinoma of the endometrium were treated with 50-mg medroxyprogesterone im twice daily for 1 year and studied to determine what effect this high dose of progesterone had on carbohydrate metabolism and liver function. Oral glucose tolerance values (fasting and 2 hour) were significantly elevated (p less than .001) at 12 and 18 months. Conjugated bilirubin was significantly elevated (p less than .01) at 18 months, aspartate aminotransferase was significantly elevated (p less than .001) at 12 and 18 months. Insulin values were raised transiently at 3 months. It is conluded that the changes in carbohydrate and liver function were small, appeared slowly, and included only a few pathologically elevated values; consequently the use of high-dose progestogen treatment for a 1-year period is considered safe.
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PMID:Effects of high-dose medroxyprogesterone treatment given for endometrial carcinoma on carbohydrate metabolism and liver function. 485 52


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