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 bimolecular association and first-order dissociation rate constants for the reactions of aminooxyacetate and hydroxylamine with the cytosolic aspartate aminotransferase (EC 2.6.1.1) of pig heart were estimated from pH 4.8 to pH 9.5. The acidic form of the enzyme (pK = 6.3) was more reactive than the unprotonated enzyme, but the rates of breakdown of the complexes were not affected by pH. The equilibrium dissociation constants, which were of the order of magnitude of 10(-7) M, were thus lowest at acidic pH values. Aminooxyacetate and hydroxylamine reacted similarly, with the former being more reactive. Glutarate and acetate inhibited the rates of formation and dissociation but had no effect on the overall equilibrium constants between enzyme and inhibitor. On the other hand, the substrate analog erythro-beta-hydroxy-L-aspartate, which forms a complex with the enzyme prosthetic group, acted competitively by preventing the inhibitors from reacting. The rate constants for formation of complexes with free pyridoxal phosphate were much less than those for the enzyme and, unlike the enzyme, hydroxylamine was more reactive than aminooxyacetate.
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PMID:Effects of ligands and pH on the reactions of aspartate aminotransferase with aminooxyacetate and hydroxylamine. 646 3

Striking differences of the environment of the phosphate group of pyridoxal-P in cytoplasmic and mitochondrial aspartate aminotransferase have been reported. Since most details of the three-dimensional structure of the active sites of these isozymes are identical, it seemed difficult to rationalize the reported differences. Therefore, the cytoplasmic isozyme was reinvestigated using 31P-NMR at 72.86 MHz. The 31P chemical shift of the cofactor of this isozyme was found to be pH-dependent with a pKa of 6.2. In the presence of 100 mM succinate or 100 mM glutarate, the 31P chemical shift of bound pyridoxal-P remains at 4.71 or 4.79 ppm, respectively, in the pH range from 5.0 to 8.0, indicating that the phosphate group of the cofactor appears to be in its dianionic form. Reduction of the internal pyridoxal-P Schiff's base dramatically increases the pKa of the phosphate group of the phosphopyridoxyl moiety of the protein to 8.3. Hence, our results on the cytoplasmic isozyme are similar to those reported for the mitochondrial isozyme.
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PMID:Phosphorus-31 nuclear magnetic resonance study on cytoplasmic aspartate aminotransferase from pig heart. A reinvestigation. 647 31

The status of thiamin, riboflavin and pyridoxine in 717 healthy children aged 1-60 months and 569 mothers aged 16-45 years attending a well-baby clinic in Bangkok were determined by using the erythrocyte enzymes, transketolase, glutathione oxidoreductase, aspartate aminotransferase and measuring the degree of stimulation with the coenzymes thiamin pyrophosphate, flavin adenine dinucleotide and pyridoxal phosphate respectively. Cut-off points for the upper limit of the normal ranges for the respective activation coefficients were established from the data obtained.
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PMID:Measurements of B1, B2, B6 status in children and their mothers attending a well-baby clinic in Bangkok. 650 Aug 37

The vitamin B6 status of 60 institutionalised elderly subjects (group A: 31 men, mean age = 77 yr and 29 women, mean age = 84 yr) and 41 healthy young adults (group B or control group: 18 men, mean age = 30 yr and 23 women, mean age = 27 yr) was evaluated using erythrocyte aspartate aminotransferase activity coefficient (alpha EGOT) and plasma pyridoxal phosphate (PLP) level (vitamin B6-deficient subjects = alpha greater than 2.0 and PLP less than 80 nmol/l). The kilocalorie, protein and pyridoxine intakes were also estimated. Regarding calories and protein, the diets may be generally considered satisfactory in respect to the French 1981 RDA. The mean dietary intake of vitamin B6 was less than 2 mg/day in all groups. Ninety per cent of the aged, 80 per cent of females in group B in contrast to 56 per cent of males in group B consumed less than their individual vitamin B6 requirements as determined by a probability method. As the incidence of vitamin B6 biochemical deficiency was much higher in the group A (71% for males and 86% for females) than in the control group (11% for males and 30% for females), it is concluded that the high incidence of biochemical vitamin B6 deficiency noted in the aged appeared more relevant from an altered metabolism of the vitamin than from a too low energy intake. Supplements with high doses of vitamin B6 to aged subjects caused a significant decrease in alpha EGOT and a significant increase in PLP levels.
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PMID:Evaluation of pyridoxine intake and pyridoxine status among aged institutionalised people. 650 Aug 42

Intraperitoneal administration of isoniazid (IN), an antituberculous drug, to mice at a dose of 100 mg/kg body weight induced significant inhibition of serum aspartate aminotransferase (AAT) in several hours. The original activity was not restored readily by in vitro treatment of the sera with pyridoxal phosphate (PLP), in contrast to the rapid activation, by the same treatment, of apoAAT in the sera from control mice. Prolonged incubation with PLP prior to the assay was required to restore most of the lost activity. Serum AAT activity enhanced by experimental and the reversal of the inhibition similarly required prolonged incubation with PLP. The results suggest the possibility that human serum AAT activity measured for clinical diagnosis may be underestimated in cases of IN overdose even if the conditions for in vitro PLP treatment of samples are sufficient for conversion of the apoenzyme to the holoenzyme.
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PMID:Inhibition of serum aspartate aminotransferase induced by isoniazid administration in mice. 653 73

The activities of aspartate aminotransferase and alanine aminotransferase in erythrocytes with and without the addition of pyridoxal phosphate were determined in healthy controls and in Indian women with cancer of the uterine cervix. The percent stimulation of the erythrocyte transferases as a result of the addition of pyridoxal phosphate was negligible in the case of normal subjects (less than 5% stimulation). In the patients with cervical cancer, a 23-35% stimulation was observed, indicating a deficiency of vitamin B6. It is not yet known whether the deficiency is the cause of the disease or due to the tumor.
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PMID:Vitamin B6 status in patients with cancer of the uterine cervix. 654 76

The relationship between pyridoxal phosphate deficiency and activities of serum and liver aminotransferases was studied in 12 patients with alcoholic hepatitis. Plasma pyridoxal phosphate and the activities of liver aminotransferases were initially decreased in the patients, as compared with mean values in controls with normal hepatic histology. Addition of pyridoxal phosphate to liver homogenates increased liver alanine aminotransferase, but not aspartate aminotransferase, in all patients with initially low plasma pyridoxal phosphate. After 1 mo of abstinence from alcohol, with intake of an adequate diet and pyridoxine supplementation, plasma pyridoxal phosphate increased in all patients with initially low values (p less than 0.02). Serum aspartate aminotransferase decreased, whereas serum alanine aminotransferase increased, resulting in a decrease in their ratio in serum (p less than 0.001). Liver alanine aminotransferase increased (p less than 0.005), whereas liver aspartate aminotransferase remained unchanged. These data suggest that pyridoxal 5'-phosphate depletion is partially responsible for the low serum alanine to aspartate aminotransferase ratio that is typical of patients with alcoholic hepatitis.
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PMID:Relationship between pyridoxal 5'-phosphate deficiency and aminotransferase levels in alcoholic hepatitis. 669 65

A number of recent studies report response of patients with carpal tunnel syndrome to pyridoxine treatment. Neurological and biochemical studies were therefore performed on six patients both before and after treatment with pyridoxine for at least 9 weeks. Free pyridoxal, pyridoxal phosphate, and total pyridoxal were assayed in plasma and neutrophils. The pyridoxal status was also estimated by assaying red cell aspartate aminotransferase. No evidence was obtained to suggest that these patients were deficient in either pyridoxal or pyridoxal phosphate. Although four of the patients claimed some partial symptomatic relief, there was no consistent improvement in clinical findings or neurophysiological measurements following pyridoxine treatment.
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PMID:Biochemical studies of pyridoxal and pyridoxal phosphate status and therapeutic trial of pyridoxine in patients with carpal tunnel syndrome. 671 84

The enzyme, aspartate aminotransferase, is a dimer consisting of two identical subunits which contain overlapping subunit regions ( Eichele , G., Ford, G.C., Glor , M., Jansonius , J.N., Mavrides , C., and Christen , P. (1979) J. Mol. Biol. 133, 161-180), suggesting the possibility of subunit interactions. The structurally similar cytosolic isozyme exhibits noncooperative binding of pyridoxal 5'-phosphate ( Boettcher , M., and Martinez -Carrion, M. (1975) Biochemistry 14, 4528-4531; Relimpio , A., Iriarte , A., Chlebowski , J.F., and Martinez -Carrion, M. (1981) J. Biol. Chem. 256, 4478-4488) in which the apoenzyme/holoenzyme hybrid dimer shows a distinctive thermal stability. Using a nonequilibrium isoelectric focusing technique, it can be shown that mitochondrial aspartate aminotransferase also binds cofactor in a noncooperative random fashion. However, differential scanning calorimetry (DSC) thermograms show different characteristics from the cytosolic form. These differences are interpreted in terms of unique subunit interactions in this isozyme. Heating to the various DSC transition temperatures shows that the anomalous DSC thermograms in partially coenzyme-saturated apoenzyme preparations are due to a selective dissociation of apoenzyme subunits into monomers which are irreversibly denatured. The remaining holoenzyme monomers reassociate and form stable holoenzyme dimers. The net result is retention of the initial concentration of holoenzyme subunits present in any given mixture. Random occupancy of active sites and similar electrophoretic and DSC patterns upon heating of partially saturated apoenzyme preparations is observed whether the coenzyme, pyridoxal phosphate or pyridoxamine phosphate alone, or borohydride-reduced Schiff's bases of coenzyme-substrate analogue derivatives are used as active site directed ligands. The latter resemble covalent enzyme-substrate intermediates.
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PMID:Coenzyme active site occupancy as an indicator of independence of the subunits of mitochondrial aspartate aminotransferase. 672 80

The inactivation mechanism of pyridoxal phosphate-linked mitochondrial aspartate transaminase (pig heart) by gostatin (5-amino-2-carboxy-4-oxo-1,4,5,6-tetrahydropyridine-3-acetic acid), a novel amino acid produced by Streptomyces sumanensis, was investigated. Gostatin is a time-dependent inhibitor of the enzyme giving an enzyme half-life of 1.8 min at 3.1 microM (25 degrees C). The kinetic properties of the inhibitor suggest that it is a suicide substrate (mechanism-based inhibitor) of the enzyme, and the observed Ki is 59 microM and Kcat is 0.11S-1 at 25 degrees C. Incubation of the enzyme with a stoichiometric amount of the inhibitor (1 mol of inhibitor/1 mol of enzyme monomer) results in complete inactivation. Spectrophotometric titration and gel filtration experiments indicate the binding of 1 mol of gostatin with 1 mol of enzyme monomer. Gostatin serves as an efficient titrant for the enzyme. Liberation of a compound having inhibitory activity against the apo-form enzyme from the enzyme-inhibitor complex under denaturing conditions suggests irreversible modification of the cofactor.
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PMID:Mechanism of inactivation of pyridoxal phosphate-linked aspartate transaminase by gostatin. 674 7


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