Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An improved understanding of medical problems of alcoholic patients can be gained from commonly encountered laboratory test results. Liver function tests--such as measures of alkaline phosphatase, gamma-glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase--may provide evidence of altered hepatic activity of different types, such as obstruction and hepatocellular injury. Other test results may indicate impaired hepatic function, such as measurements of albumin, bilirubin, prothrombin time, and blood urea nitrogen. Alterations are also common in electrolytes, blood glucose, magnesium, phosphate, uric acid, and acid-base balance. Disturbances in hematologic function are not infrequent in alcoholic patients, including anemias from many causes, altered granulocyte responses, and thrombocytopenia.
 ...
PMID:Clinical significance in alcoholic patients of commonly encountered laboratory test results. 159 68

Chewing sticks or Meswaks are used for teeth cleaning in many parts of the world. They contain substances that may reduce caries and periodontal disease. The present study consisted of 2 parts. In a short-term experiment, volunteers chewed on an inert eliciting agent (pyrogen-free rubber) and then a piece of Meswak, each for 5 min. For the medium-term experiment, volunteers brushed with either Meswak or a conventional toothbrush 5 x a day for 2 weeks. Saliva produced immediately after chewing Meswak showed statistically significant increases in calcium and chloride, but decreases in phosphate and pH as compared with controls. In the medium-term experiment, saliva samples collected 4 h after the last use of Meswak or toothbrush showed no significant differences in any of the components examined (calcium, magnesium, chloride, phosphate, IgA, IgG, lactate dehydrogenase and aspartate transaminase). Gingival and plaque indices, however, were significantly lower after brushing with Meswak. Salivary calcium promotes mineralization of tooth enamel and chloride inhibits calculus formation. Our results thus indicate that Meswak releases substances into saliva that could improve oral health. Calcium and chloride values were similar to those of controls after 4 h and thus frequent use of Meswak may be necessary to maintain a favorable salivary environment.
 ...
PMID:The immediate- and medium-term effects of Meswak on the composition of mixed saliva. 160 35

Asp222 is an invariant residue in all known sequences of aspartate aminotransferases from a variety of sources and is located within a distance of strong ionic interaction with N(1) of the coenzyme, pyridoxal 5'-phosphate (PLP), or pyridoxamine 5'-phosphate (PMP). This residue of Escherichia coli aspartate aminotransferase was replaced by Ala, Asn, or Glu by site-directed mutagenesis. The PLP form of the mutant enzyme D222E showed pH-dependent spectral changes with a pKa value of 6.44 for the protonation of the internal aldimine bond, slightly lower than that (6.7) for the wild-type enzyme. In contrast, the internal aldimine bond in the D222A or D222N enzyme did not titrate over the pH range 5.3-9.5, and a 430-nm band attributed to the protonated aldimine persisted even at high pH. The binding affinity of the D222A and D222N enzymes for PMP decreased by 3 orders of magnitude as compared to that of the wild-type enzyme. Pre-steady-state half-transamination reactions of all the mutant enzymes with substrates exhibited anomalous progress curves comprising multiphasic exponential processes, which were accounted for by postulating several kinetically different enzyme species for both the PLP and PMP forms of each mutant enzyme. While the replacement of Asp222 by Glu yielded fairly active enzyme species, the replacement by Ala and Asn resulted in 8600- and 20,000-fold decreases, respectively, in the catalytic efficiency (kmax/Kd value for the most active species of each mutant enzyme) in the reactions of the PLP form with aspartate. In contrast, the catalytic efficiency of the PMP form of the D222A or D222N enzyme with 2-oxoglutarate was still retained at a level as high as 2-10% of that of the wild-type enzyme. The presteady-state reactions of these two mutant enzymes with [2-2H]aspartate revealed a deuterium isotope effect (kH/kD = 6.0) greater than that [kH/kD = 2.2; Kuramitsu, S., Hiromi, K., Hayashi, H., Morino, Y., & Kagamiyama, H. (1990) Biochemistry 29, 5469-5476] for the wild-type enzyme. These findings indicate that the presence of a negatively charged residue at position 222 is particularly critical for the withdrawal of the alpha-proton of the amino acid substrate and accelerates this rate-determining step by about 5 kcal.mol-1. Thus it is concluded that Asp222 serves as a protein ligand tethering the coenzyme in a productive mode within the active site and stabilizes the protonated N(1) of the coenzyme to strengthen the electron-withdrawing capacity of the coenzyme.
 ...
PMID:Role of Asp222 in the catalytic mechanism of Escherichia coli aspartate aminotransferase: the amino acid residue which enhances the function of the enzyme-bound coenzyme pyridoxal 5'-phosphate. 161 Aug 31

Equilibrium dissociation and unfolding of dimeric aspartate aminotransferase from Escherichia coli proceeds via two compact monomeric intermediates which have similar hydrodynamic volumes but different fluorescence properties. We probed binding of the coenzyme pyridoxal 5'-phosphate to these intermediates by coupling fluorescence detection to size-exclusion HPLC. This procedure gave additionally an internal conformational probe of the unfolding transitions of the enzyme. It was shown that the first intermediate, M, is able to bind the coenzyme, whereas the second intermediate, M*, is not. It is likely that M is the correctly folded monomer of the protein.
 ...
PMID:Coenzyme binding of a folding intermediate of aspartate aminotransferase detected by HPLC fluorescence measurements. 164 99

The Y70F mutant of aspartate aminotransferase has reduced affinity for coenzymes compared to the wild type. The equilibrium dissociation constants for pyridoxamine phosphate (PMP) holoenzymes, KPMPdiss, were determined from the association and dissociation rate constants to be 1.3 nM and 30 nM for the wild type and mutant, respectively. This increase in KPMPdiss for Y70F is due to a 27-fold increase in the dissociation rate constant. Pyridoxal phosphate (PLP) association kinetics are complex, with three kinetic processes detectable for wild type and two for Y70F. A directly determined, accurate value of KPLPdiss for wild type enzyme has been difficult to obtain because of the low value of this constant. The values of KPLPdiss for the holoenzymes were determined indirectly through the measured values for KPMPdiss, glutamate-alpha-ketoglutarate half-reaction equilibrium constants, and the equilibrium constant for the transamination of PLP by glutamate catalyzed by Y70F. The values of KPLPdiss obtained by this procedure are 0.4 pM for wild type and 40 pM for Y70F. The increases in KPMPdiss and KPLPdiss for Y70F correspond to delta delta G values of 1.9 and 2.7 kcal/mol, respectively, and are directly attributed to the loss of the hydrogen bond from the phenolic hydroxyl group of Tyr70 to the coenzyme phosphate. The delta G for association of PLP with wild type enzyme is 4.7 kcal/mol more favorable than that for PMP.
 ...
PMID:Kinetics and equilibria for the reactions of coenzymes with wild type and the Y70F mutant of Escherichia coli aspartate aminotransferase. 167 70

Applying catalytic enzyme histochemistry, glutamate dehydrogenase (GDH) and phosphate activated glutaminase (PAG) were demonstrated at the light microscopic level, and aspartate aminotransferase (AAT) was detected at the electron microscopic level. GDH staining appeared preferentially in glial cells (Bergmann glia and astrocytes), whereas AAT was localized only in neuronal structures. Cytoplasmic AAT was demonstrated in the perikarya and terminal plexus of basket cells, in the perikarya of stellate cells, in about 60% of the granule cells, in mossy fiber boutons, in numerous small boutons in the molecular layer, and in the axoplasm of numerous myelinated and unmyelinated fibers. PAG was observed in both neuronal structures (perikarya of granule and Purkinje cells) and in astrocytes and Bergmann glia.
 ...
PMID:Histochemistry of glutamate metabolizing enzymes in the rat cerebellar cortex. 168 39

Lys-258 of aspartate aminotransferase forms a Schiff base with pyridoxal phosphate and is responsible for catalysis of the 1,3-prototropic shift central to the transamination reaction sequence. Substitution of arginine for Lys-258 stabilizes the otherwise elusive quinonoid intermediate, as assessed by the long wavelength absorption bands observed in the reactions of this mutant with several amino acid substrates. The external aldimine intermediate is not detectable during reactions of this mutant with amino acids, although the inhibitor alpha-methylaspartate does slowly and stably form this species. These results suggest that external aldimine formation is one of the rate-determining steps of the reaction. The pyridoxamine-5'-phosphate-like enzyme form (330-nm absorption maximum) is unreactive toward keto acid substrates, and the coenzyme bound to this species is not dissociable from the protein.
 ...
PMID:The K258R mutant of aspartate aminotransferase stabilizes the quinonoid intermediate. 174 61

This study was undertaken to determine whether or not prostaglandin I2 (PGI2) analog pretreatment could successfully preserve organ viability after warm hepatic ischemia in rats. Although 120-min ischemia of the liver did not permit survival in rats administered normal saline solution (NS group) before warm ischemia, the survival rate of PGI2 analogue (500 ng/kg/min)-treated rats (PG group) significantly improved to 57% (P less than 0.05). Recirculation following 120-min hepatic ischemia in the NS group resulted in no improvement of B-phosphorus of the ATP (B-ATP)/inorganic phosphate (Pi) ratio measured by 31P nuclear magnetic resonance, a marked increase in the serum aspartate aminotransferase (SAST) level, and an increase in the malondialdehyde (MDA) level in liver tissue. In the PG group, the B-ATP/Pi ratio was significantly improved (P less than 0.05), the elevation in SAST was also markedly suppressed (P less than 0.05), and the MDA level of the liver was lowered more than that in the NS group. Severe congestion and extensive vacuolization of hepatocytes from the peripheral to the midzonal areas were histologically exhibited with single-cell necrosis in the NS group. There were fewer histological alterations of the liver and these coincided with the changes in other parameters in the PG group. Our results indicate that PGI2 analog reduces warm ischemic injury of the liver and provides greater protection for organs to be transplanted.
 ...
PMID:The beneficial effect of a prostaglandin I2 analog on ischemic rat liver. 175 84

Effects of administration of triflupromazine were evaluated in 11 adult domesticated camels (Camelus dromedarius) weighing 403 +/- 29.5 kg (Mean +/- SE). Six camels were used to evaluate sedative properties of the drug and its effects on haematological and blood biochemical parameters. In the remaining 5 camels, effects on haemodynamics, acid base status and blood gases were studied. In all the animals triflupromazine was administered intramuscularly in the gluteal region at the rate of 2 mg/kg. Camels voluntarily sat down 48.9 +/- 5.4 min after administration of the drug but stood up again if disturbed. Drowsiness, drooping of lower lip and salivation were evident. The animals stood on their own and started walking with ataxia after 159 +/- 7 min and recovered completely from the effect of drug within 259 +/- 23 min. The drug caused a significant tachycardia and a moderate hypotension. The decrease in central venous pressure was also significant. Rectal temperature, respiratory rate, acid base status, blood gases, haemoglobin concentration, packed cell volume, total erythrocyte count, total leucocyte count, differential leukocyte count, blood urea nitrogen, plasma alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, blood glucose and plasma concentrations of sodium, potassium, chloride and inorganic phosphate were not significantly affected by triflupromazine.
 ...
PMID:Evaluation of triflupromazine as a sedative in camels (Camelus dromedarius). 177 79

Several clinical chemical blood variables were compared, in order to evaluate the differences between Na heparinized plasma and serum samples. Samples from 45 healthy horses were used. No differences between the two sample substrates were found for aspartate aminotransferase, lactate dehydrogenase, lactate dehydrogenase-isoenzymes, creatine kinase, alkaline phosphatase, bilirubin, cholesterol, urea, total protein, alpha-globulin, gamma-globulin, albumin, calcium (Ca), phosphate (P), sodium (Na) and potassium (K). gamma-Glutamyltransferase and beta-globulin were significantly higher in heparinized plasma than in serum (each p less than 0.05) while magnesium (Mg) was lower (p less than 0.05). From the horse group used for the study, thoroughbreds in racing condition had significantly higher aspartate aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, bilirubin, P and Mg as well as lower Ca and K values than riding horses, irrespective of the sample substrate used. It was concluded that expect for gamma-glutamyltransferase, beta-globulin and Mg, there was no significant difference between the clinical chemical variables of Na heparinized plasma and serum samples.
 ...
PMID:Comparison of clinical chemical variables in blood plasma and serum of horses. 179 11


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>