Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between nitrogen assimilation, metabolism and aflatoxin formation has been investigated in a toxigenic and a non-toxigenic strain of Aspergillus parasiticus. Ammonia from the medium is mainly assimilated via NADP-requiring glutamate dehydrogenase. During growth NAD-requiring glutamate dehydrogenase followed an inverse pattern of activity with respect to NADP glutamate dehydrogenase. Alpha-ketoglutarate, the product of NAD glutamate dehydrogenase, stimulated acetate incorporation into aflatoxins. Glutamine synthetase, ornithine transcarbamylase, both utilizing glutamate as substrate were assayed under different growth conditions. An important regulatory role for glutamine synthetase is suggested. The metabolic route of asparagine utilization was also investigated. Both the known pathways, glutamate oxaloacetate transaminase and glutamate pyruvate transaminase are operative simultaneously.
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PMID:Nitrogen metabolism in Aspergillus parasiticus NRRL 3240 and A. flavus NRRL 3537 in relation to aflatoxin production. 287 96

Malate dehydrogenase (EC 1.1.1.37) was immobilized on the lower groove of the dialyzer plate used for serum aspartate aminotransferase determination in the AutoAnalyzer II system. Immobilization was effected by covalently attaching malate dehydrogenase to the inner surface of the groove which was previously activated by treatment with glutaraldehyde at room temperature. The immobilized malate dehydrogenase catalyzed the reaction between oxaloacetate and NADH to form NAD in the coupled reaction originally proposed by Karmen. Results of the present method correlated well with those obtained by the Technicon SMA II system in which malate dehydrogenase is in solution (n = 99; r = 0.99; t = 0.30). The activity of immobilized malate dehydrogenase on the dialyzer groove was sufficient to measure serum aspartate aminotransferase for at least one month with continuous use. The stability of immobilized malate dehydrogenase was also dependent on the number of samples determined. The dialyzer plate is a reusable solid matrix for malate dehydrogenase immobilization. The expense of the present method is only half the cost of the method in which malate dehydrogenase is in solution.
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PMID:Use of malate dehydrogenase immobilized on the dialyzer groove of the Autoanalyzer II for serum aspartate aminotransferase determination. 311 24

The RS-isomers of beta-mercapto-alpha-ketoglutarate, beta-methylmercapto-alpha-ketoglutarate and beta-methylmercapto-alpha-hydroxyglutarate have been synthesized. Beta-Mercapto-alpha-ketoglutarate was a potent inhibitor, competitive with isocitrate and noncompetitive with NADP+, of the mitochondrial NADP-specific isozyme from pig heart (Ki = 5 nM; Km (DL-isocitrate)/Ki(RS-beta-mercapto-alpha-ketoglutarate) = 650) and pig liver, the cytosolic isozyme from pig liver (I0.5 = 23 nM), and the NADP-linked enzymes from yeast (Ki = 58 nM) and Escherichia coli (Ki = 58 nM) at pH 7.4 and with Mg2+ as activator. beta-Mercapto-alpha-ketoglutarate was also an effective inhibitor of NADP-isocitrate-dehydrogenase activity in intact liver mitochondria. beta-Mercapto-alpha-ketoglutarate was a much less potent inhibitor for heart NAD-isocitrate dehydrogenase (Ki = 520 nM) than for the NADP-specific enzyme. beta-Methylmercapto-alpha-ketoglutarate (I0.5 = 10 microM) was a much less effective inhibitor than the beta-mercapto derivative for heart NADP-isocitrate dehydrogenase. The beta-sulfur substituted alpha-ketoglutarates were substrates for the oxidation of NADPH by heart NADP-isocitrate dehydrogenase without requiring CO2. beta-Methylmercapto-alpha-hydroxyglutarate, the expected product of reduction of beta-methylmercapto-alpha-ketoglutarate, did not cause reduction of NADP+ but it was an inhibitor competitive with isocitrate for NADP-isocitrate dehydrogenase. The beta-sulfur substituted alpha-ketoglutarate derivatives were alternate substrates for alpha-ketoglutarate dehydrogenase and the cytosolic and mitochondrial isozymes of heart aspartate aminotransferase but had no effect on glutamate dehydrogenase or alanine aminotransferase.
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PMID:beta-Sulfur substituted alpha-ketoglutarates as inhibitors and alternate substrates for isocitrate dehydrogenases and certain other enzymes. 394 94

Current evidence suggests that mitochondrial matrix enzymes exist in solid-state, multienzyme complexes in vivo. Addition of polyethylene glycol to a solution containing malate dehydrogenase and citrate synthase generates such a solid-state, enzyme complex in vitro at enzyme concentrations permitting kinetic measurements. Suspensions of the isolated, solid-state, hetero-complex of these enzymes were used to study the coupled reactions of citrate synthesis from malate, NAD, and CoASAc. The particles appear to be about 1 microgram in diameter. Considering the ratio of enzyme to oxalacetate molecules in or at the surface of the solid-state particles, one would expect oxalacetate to be converted to citrate within a few molecular distances of the site of oxalacetate generation. This model of "substrate channeling" (or alternatively a direct transfer of oxalacetate between enzymes) is supported by experiments with excess aspartate aminotransferase and glutamate added to the solution phase to give a reaction competing with the synthase for bulk phase oxalacetate. Quantities of aminotransferase that reduce the citrate reaction rate with soluble dehydrogenase and synthase by 90% do not significantly affect rates with comparable amounts of the dehydrogenase-synthase complex. We suggest that similar substrate channeling can occur in vivo and discuss the possible advantages provided thereby.
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PMID:Substrate channeling of oxalacetate in solid-state complexes of malate dehydrogenase and citrate synthase. 406 62

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

Treatment of rat liver mitochondria with digitonin followed by differential centrifugation was used to resolve the intramitochondrial localization of both soluble and particulate enzymes. Rat liver mitochondria were separated into three fractions: inner membrane plus matrix, outer membrane, and a soluble fraction containing enzymes localized between the membranes plus some solublized outer membrane. Monoamine oxidase, kynurenine hydroxylase, and rotenone-insensitive NADH-cytochrome c reductase were found primarily in the outer membrane fraction. Succinate-cytochrome c reductase, succinate dehydrogenase, cytochrome oxidase, beta-hydroxybutyrate dehydrogenase, alpha-ketoglutarate dehydrogenase, lipoamide dehydrogenase, NAD- and NADH-isocitrate dehydrogenase, glutamate dehydrogenase, aspartate aminotransferase, and ornithine transcarbamoylase were found in the inner membrane-matrix fraction. Nucleoside diphosphokinase was found in both the outer membrane and soluble fractions; this suggests a dual localization. Adenylate kinase was found entirely in the soluble fraction and was released at a lower digitonin concentration than was the outer membrane; this suggests that this enzyme is localized between the two membranes. The inner membrane-matrix fraction was separated into inner membrane and matrix by treatment with the nonionic detergent Lubrol, and this separation was used as a basis for calculating the relative protein content of the mitochondrial components. The inner membrane-matrix fraction retained a high degree of morphological and biochemical integrity and exhibited a high respiratory rate and respiratory control when assayed in a sucrose-mannitol medium containing EDTA.
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PMID:Enzymatic properties of the inner and outer membranes of rat liver mitochondria. 569 70

The mechanism of ammonia assimilation in Methanosarcina barkeri and Methanobacterium thermoautotrophicum was documented by analysis of enzyme activities, 13NH3 incorporation studies, and comparison of growth and enzyme activity levels in continuous culture. Glutamate accounted for 65 and 52% of the total amino acids in the soluble pools of M. barkeri and M. thermoautotrophicum. Both organisms contained significant activities of glutamine synthetase, glutamate synthase, glutamate oxaloacetate transaminase, and glutamate pyruvate transaminase. Hydrogen-reduced deazaflavin-factor 420 or flavin mononucleotide but not NAD, NADP, or ferredoxin was used as the electron donor for glutamate synthase in M. barkeri. Glutamate dehydrogenase activity was not detected in either organism, but alanine dehydrogenase activity was present in M. thermoautotrophicum. The in vivo activity of the glutamine synthetase was verified in M. thermoautotrophicum by analysis of 13NH3 incorporation into glutamine, glutamate, and alanine. Alanine dehydrogenase and glutamine synthetase activity varied in response to [NH4+] when M. thermoautotrophicum was cultured in a chemostat with cysteine as the sulfur source. Alanine dehydrogenase activity and growth yield (grams of cells/mole of methane) were highest when the organism was cultured with excess ammonia, whereas growth yield was lower and glutamine synthetase was maximal when ammonia was limiting.
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PMID:Ammonia assimilation and synthesis of alanine, aspartate, and glutamate in Methanosarcina barkeri and Methanobacterium thermoautotrophicum. 612 78

Pregnant F-344 rats were exposed by intubation to a single dose (35 mg/kg) of 1,2-dimethylhydrazine dihydrochloride or to an acetate buffer on day 14 of gestation. A detailed examination of the effects of this dose of 1,2-dimethylhydrazine on brush border enzymes in the offspring was performed. Changes in the liver and colon levels of the alpha-glycerophosphate and malate/aspartate substrate cycle enzymes were measured during the development; at days 17 and 20 of gestation and at 2, 6, 13, 20, 27, 55, 110 days and 1 year after birth. It is concluded that metabolic energy enzymes, glutamate oxaloacetate transaminase and malate dehydrogenase, are more sensitive to 1,2-dimethylhydrazine treatment than are the brush border hydrolases or NAD- and Fp-linked alpha-glycerophosphate dehydrogenases.
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PMID:Development of rat liver and colon substrate cycle enzymes in offspring with and without prenatal exposure to a carcinogenic dose of 1,2-dimethylhydrazine. 614 Jan 24

1. The acute oral LD50 and chronic LC50 toxicity values for ethylene dibromide (EDB) were estimated for japanese quail. 2. Single sub-acute oral and intraperitoneal doses of EDB (1/2 LD50) and chronic oral doses of EDB (1/3 LC50) were administered to quail in order to characterise the sub-lethal effects of EDB residues. 3. At 24 h after sub-acute dosing, relative liver weight, plasma aspartate aminotransferase (AT) [EC 2.6.1.1] and L-iditol (sorbitol) dehydrogenase (SDH) [EC 1.1.1.14] were elevated and decreases were found in hepatic total lipid, total protein, AT and glutamic dehydrogenase (NAD (P)+) (GDH) and plasma cholinesterase (ChE) [EC 3.1.1.8] and total lipid. 4. Following chronic administration, elevations in relative liver weight, plasma ChE and total lipid, haemoglobin and haematocrit were found and hepatic AT, GDH and total lipid were decreased. 5. The changes in hepatic and plasma enzymes and constituents are discussed in relation to possible biphasic effects resulting from EDB exposure.
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PMID:A study on the toxicity and the biochemical effects of ethylene dibromide in the Japanese quail. 702 16

1. Erythrocytes (RBC) from control and marginally riboflavin-deficient subjects were fractionated into nine fractions using a discrete density gradient. 2. Glutathione reductase (NAD(P)H: glutathione oxidoreductase; EC 1.6.4.2) activity and aspartate aminotransferase (EC 2.6.1.1) activity (with and without the appropriate co-enzymes) reduced glutathione, methaemoglobin, sulphaemoglobin and oxyhaemoglobin and susceptibility to peroxide were measured in RBC in the different fractions. 3. Glutathione reductase and aspartate aminotransferase activities and concentrations of reduced glutathione and oxyhaemoglobin all declined with age, while methaemogloblin, sulphaemoglobin and susceptibility to peroxide increased with age. 4. The only significant differences noted in the RBC from marginally-riboflavin-deficient subjects by comparison with controls, were lower glutathione reductase activities and higher concentrations of methaemoglobin. 5. The role of riboflavin in those systems controlling RBC integrity is discussed.
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PMID:Riboflavin deficiency in man: effects on haemoglobin and reduced glutathione in erythrocytes of different ages. 728 95


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