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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphypyridoxyl trifluoroethylamine has been synthesized as an active site-directed 19F NMR probe for aspartate transaminase. This coenzyme derivative adds stoichiometrically to the apotransaminase as observed by both fluorescence and circular dichroism measurements. The fluorinated phosphypyridoxamine derivative, when bound to the apotransaminase, will not dissociate upon extensive dialysis or passage through Sephadex G-25. The compound behaves as a pyridoxamine phosphate derivative and not as a coenzyme-substrate complex, since both competing anions and dicarboxylic acid inhibitors still bind to the phosphopyridoxyl trifluoroethylamine enzyme. The 19F NMR spectra of the enzyme-bound phosphopyridoxyl trifluoroethylamine were measured as a function of pH, ionic strength, and temperature. The 19F MNR of the enzyme-bound coenzyme derivative revealed no predetermined asymmetry in the subunits of aspartate transaminase insolution in terms of differences in chemical shift or resonance line shape between the two environments. A pH-dependent chemical shift change of the single 19F resonance was observed, which is consistent with the influence of a single ionization with an apparent pKa of 8.4 in 0.10 M KCl at 30 degrees. Increasing the ionic strength resulted in increasing values for the observed pKa, the highest recorded value was 9.1 in 3.0 M KCl. The temperature dependence of the pH titration of the chemical shift gives deltaH' of ionization of 10.5 kcal/mol. The evidence suggests a possible epsilon-amino group, electrostatically affected by positive charges, being responsible for the titration effect of the active site-bound fluorine derivative of pyridoxamine phosphate.
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PMID:Fluorine-19 as a covalent active site-directed magnetic resonance probe in aspartate transaminase. 0 32

At pH 8.0 aspartate aminotransferase (L-aspartate:2-oxoglutarate aminotransferase, EC 2.6.1.1) reacts with the modified substrate, erythro-beta-hydroxy-L-aspartate, to form a mixture of enzyme-substrate complexes absorbing at 492 nm. A variety of dicarboxylic acids were studied spectrophotometrically as competitive inhibitors of this reaction. All of the inhibitory dicarboxylic acids form a complex with the enzyme, absorbing at 362 nm. In addition, some of the dicarboxylic acids form a protonated complex absorbing at about 435 nm. This complex, which is the conjugate acid of that absorbing at 362 nm, is formed only by those dicarboxylic acids which can assume a configuration in which the two carboxyl groups are positioned as in maleic acid. Bulky substituents, such as aromatic rings or even methyl groups, prevent the formation of the protonated complex, presumably because of steric restrictions at the active site. Substitution of the central carbon atom of glutaric acid by heteroatoms of increasing charge density results in a progressive decrease in inhibitory effectiveness, at pH 8, primarily due to a loss of this pH-dependent stabilization of the enzyme-dicarboxylic acid complex. Acids with an aromatic ring are among the most potent dicarboxylic acid inhibitors of this enzyme in spite of the fact that they do not undergo the pH-dependent stabilization of their enzyme complexes. From these observations it was concluded that the affinity of aspartate aminotransferase for dicarboxylic acids is determined as much by the mechanism of binding as by the solvation and steric effects.
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PMID:Factors contributing to the inhibition of aspartate aminotransferase by dicarboxylic acids. 24 51

We present a new model for E. coli tyrosine aminotransferase based on the X-ray structures of the wild type and Val39Leu mutant of E. coli aspartate aminotransferase and computer simulation studies. Active site characteristics of the model are correlated with experimental observations on the specificity of these enzymes towards aromatic/dicarboxylic acid substrates.
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PMID:Computational approach towards the three-dimensional structure of E. coli tyrosine aminotransferase. 135 27

A reinvestigation of the effects of pH and salt concentration on the proton and dicarboxylic acid dissociation constants of pig heart aspartate aminotransferase shows that both anions and cations were involved concomitantly, both as stoichiometric reactants and bioenergetically. Equations are presented which can be used experimentally, to determine the numbers of salt ions (their thermodynamic stoichiometries) involved in biochemical equilibria such as proton and ligand dissociations from macromolecules. These equations were used to reinvestigate the effects of salts on the chromophoric pKa of the enzyme prosthetic group, the interaction of the enzyme with dicarboxylic acids, and the overall equilibrium for the transamination half-reaction.
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PMID:Thermodynamic bookkeeping: a reinvestigation of proton and dicarboxylic acid binding to aspartate aminotransferase. 254 52

Evoked release of glutamate and aspartate from cultured cerebellar granule cells was studied after preincubation of the cells in tissue culture medium with glucose (6.5 mM), glutamine (1.0 mM), D[3H] aspartate and in some cases aminooxyacetate (5.0 mM) or phenylsuccinate (5.0 mM). The release of endogenous amino acids and of D-[3H] aspartate was measured under physiological and depolarizing (56 mM KCl) conditions both in the presence and absence of calcium (1.0 mM), glutamine (1.0 mM), aminooxyacetate (5.0 mM) and phenylsuccinate (5.0 mM). The cellular content of glutamate and aspartate was also determined. Of the endogenous amino acids only glutamate was released in a transmitter fashion and newly synthesized glutamate was released preferentially to exogenously supplied D-[3H] aspartate, a marker for exogenous glutamate. Evoked release of endogenous glutamate was reduced or completely abolished by respectively, aminooxyacetate and phenylsuccinate. In contrast, the release of D-[3H] aspartate was increased reflecting an unaffected release of exogenous glutamate and an increased "psuedospecific radioactivity" of the glutamate transmitter pool. Since aminooxyacetate and phenylsuccinate inhibit respectively aspartate aminotransferase and mitochondrial keto-dicarboxylic acid transport it is concluded that replenishment of the glutamate transmitter pool from glutamine, formed in the mitochondrial compartment by the action of glutaminase requires the simultaneous operation of mitochondrial keto-dicarboxylic acid transport and aspartate aminotransferase which is localized both intra- and extra-mitochondrially. The purpose of the latter enzyme apparently is to catalyze both intra- and extra-mitochondrial transamination of alpha-ketoglutarate which is formed intramitochondrially from the glutamate carbon skeleton and transferred across the mitochondrial membrane to the cytosol where transmitter glutamate is formed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of aspartate aminotransferase and mitochondrial dicarboxylate transport for release of endogenously and exogenously supplied neurotransmitter in glutamatergic neurons. 256 74

The effects on metabolism of the fluorinated dicarboxylic acid, perfluorosuccinate, were examined in hepatocytes from fasted rats. Perfluorosuccinate (5 mM) inhibited gluconeogenesis from lactate by 80% and from pyruvate by 40%. Significant inhibition (up to 30%) occurred at a concentration of perfluorosuccinate of 50 microM. Cellular ATP levels were not affected by perfluorosuccinate, nor was the rate of formation of ketone bodies from palmitate, although the ratio [3-hydroxybutyrate]/[acetoacetate] was increased up to 5-fold relative to the control. An increased concentration of cellular L-malate was measured in the presence of perfluorosuccinate but this did not reflect inhibition of malate transport between the mitochondrial and cytoplasmic compartments. In addition, ethanol oxidation by hepatocytes was inhibited 25% by 1 mM perfluorosuccinate. Ureogenesis from ammonia was relatively insensitive to inhibition by perfluorosuccinate. In cytoplasmic extracts of rat liver, the activities of phosphoenolpyruvate carboxykinase and aspartate aminotransferase were inhibited 40-50% and 23%, respectively, by 1 mM perfluorosuccinate. The observed metabolic effects of perfluorosuccinate are consistent with inhibition of the activities of phosphoenolpyruvate carboxykinase and aspartate aminotransferase within the cytoplasm.
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PMID:The characterization of perfluorosuccinate as an inhibitor of gluconeogenesis in isolated rat hepatocytes. 277 10

A choline deficient L-amino acid defined (CDAA) diet led to the development of liver cirrhosis in male Wistar rats after 16 weeks. A new prolyl 4-hydroxylase inhibitor, 2,4-pyridine dicarboxylic acid bis [(2-methoxyethyl amide)] (HOE 077), prevented liver fibrosis in a dose-dependent manner without a reduction in increased serum alanine aminotransferase and aspartate aminotransferase in parallel with a reduction in preneoplastic enzyme-altered lesions stained with anti-glutathione S-transferase placental form antibody. HOE 077 reduced the increase in serum procollagen III peptide (PIIIP) in a dose-dependent manner and in proportion to the reduction in mRNA expression of type III procollagen in the liver of rats fed a CDAA diet.
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PMID:New prolyl 4-hydroxylase inhibitor reduces procollagen gene expression and enzyme-altered lesions in rat liver cirrhosis. 858 46

The activities of certain enzymes related to the carbon assimilation pathway in whole leaves, mesophyll cell extracts, and bundle sheath extracts of the C(4) plant Panicum miliaceum have been measured and compared on a chlorophyll basis. Enzymes of the C(4) dicarboxylic acid pathway-phosphoenolpyruvate carboxylase and NADP-malic dehydrogenase-were localized in mesophyll cells. Carbonic anhydrase was also localized in mesophyll cell extracts. Ribose 5-phosphate isomerase, ribulose 5-phosphate kinase, and ribulose diphosphate carboxylase-enzymes of the reductive pentose phosphate pathway-were predominantly localized in bundle sheath extracts. High activities of aspartate and alanine transaminases and glyceraldehyde-3-P dehydrogenase were found about equally distributed between the photosynthetic cell types. P. miliaceum had low malic enzyme activity in both mesophyll and bundle sheath extracts.Isolated bundle sheath cells were capable of converting aspartate to oxalacetate at rates approaching the aspartate transaminase activity of bundle sheath extracts. The bundle sheath cells had a light induced CO(2) fixation of 23 mumoles of CO(2)/mg chl.hr in the absence of exogenous substrates.The photorespiratory enzymes, hydroxypyruvate reductase and glycolic oxidase, were about 3 fold higher in bundle sheath extracts than in mesophyll extracts when compared on a chlorophyll basis.
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PMID:Metabolic Activities in Extracts of Mesophyll and Bundle Sheath Cells of Panicum miliaceum (L.) in Relation to the C(4) Dicarboxylic Acid Pathway of Photosynthesis. 1665 52

Mesophyll cells and bundle sheath strands isolated from leaves of the C(4) plant Digitaria sanguinalis (L.) Scop. are capable of utilizing aspartate as a Hill oxidant. The resulting O(2) evolution upon illumination depends on the presence of 2-oxoglutarate, is inhibited by 3-(3,4-dichlorophenyl)-1,1-dimethylurea, and is stimulated by methylamine. The rate of aspartate-dependent O(2) evolution with mesophyll cells was similar to those with phosphoenolpyruvate + CO(2) or with oxalacetate. Amino-oxyacetate, an inhibitor of aspartate aminotransferase, inhibited the aspartate-dependent O(2) evolution. Aspartate aminotransferase and NADP(+) -malate dehydrogenase are located in the mesophyll chloroplasts. These data suggest that aspartate is converted to oxalacetate via aspartate aminotransferase in the chloroplasts of mesophyll cells and that oxalacetate is subsequently reduced to malate, which is coupled to the photochemical evolution of O(2). This suggestion is further verified by the inhibition of phosphoenolpyruvate-dependent (14)CO(2) fixation by aspartate + 2-oxoglutarate, which presumably acts as oxalacetate and competes with phosphoenolpyruvate + CO(2) for NADPH. dl-Glyceraldehyde inhibited aspartate-dependent O(2) evolution in the bundle sheath strands but not in the mesophyll cells. The data indicate that aspartate may be converted to malate in both mesophyll and bundle sheath cells. In NADP(+) -malic enzyme species, aspartate may exist as a C(4)-dicarboxylic acid reservoir which can contribute to the C(4) cycle through its conversion to malate.
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PMID:Photosynthetic Metabolism of Aspartate in Mesophyll and Bundle Sheath Cells Isolated from Digitaria sanguinalis (L.) Scop., a NADP-Malic Enzyme C(4) Plant. 1666 95

Vibrio parahaemolyticus ATCC 27519 was chosen as indicator of aquacultural pathogenic bacteria to determine the antibacterial activity and mechanism of copper-bearing montmorillonite (Cu-MMT) in vitro. The results indicated that montmorillonite (MMT) had no antibacterial activity. The minimum inhibitory concentration (MIC) and bactericidal concentration (MBC) of Cu-MMT on Vibrio parahaemolyticus were 75 and 300 mg/L, respectively. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) of bacteria were examined and the results showed treatment with Cu-MMT could lead to significant release of intracellular enzymes from the tested bacteria suggesting that the permeability of the cell membrane increased and bacteria suffered injury. Three typical inhibitors (malonic acid, iodine acetic acid and phosphate sodium) were used to further study the inhibitory pathways of respiratory metabolism. Cu-MMT effectively inhibited respiratory metabolism of Vibrio parahaemolyticus, with the respiratory inhibition percent (I(R)) of 31.8%. The respiratory superposing inhibition percent after addition of phosphate sodium, iodine acetic acid and malonic acid was 48.6%, 27.8% and 17.5%, respectively. These results indicated that the effect of malonic acid on superposing inhibition percent of Cu-MMT for bacteria is the lowest; thus, the synergic action between Cu-MMT and malonic acid is the weakest, indicating that they inhibited the same pathway of respiratory metabolism, i.e. the TCA pathway, which is the most important pathway of carbohydrate metabolism. The atomic force microscope image of Vibrio parahaemolyticus exposed to Cu-MMT showed that Cu-MMT could rupture the bacterial cell membrane.
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PMID:[Study on the antibacterial mechanisms of copper-bearing montmorillonite]. 1693 15


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