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)

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.
J Biol Chem 1991 Dec 15
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.
Transplantation 1991 Dec
PMID:The beneficial effect of a prostaglandin I2 analog on ischemic rat liver. 175 84

We have isolated an alfalfa leaf cDNA clone that encodes aspartate aminotransferase (AAT, EC 2.6.1.1) by direct complementation of an Escherichia coli aspartate auxotroph with a plasmid cDNA library. DNA sequence analysis of the recombinant plasmid, pMU1, revealed that a 1514 bp cDNA was inserted in the correct orientation and in-frame with the start of the lacZ coding sequence in the vector, pUC18. The resulting fusion protein is predicted to be 424 amino acids in length with a molecular weight of 46387 Daltons. The cDNA-encoded protein has a characteristic pyridoxal phosphate attachment site motif and has substantial amino acid sequence homology to both animal and bacterial AATs. Plasmid pMU1 encodes an AAT with a Km for aspartate of 3.3 mM, a Km for 2-oxoglutarate of 0.28 mM, and a pH optimum between 8.0 and 8.5. Several lines of evidence including Western blot analysis, the isoelectric point of the encoded protein, and the effect of pH on the activity of the fusion protein, suggest that the cDNA encodes the isozyme AAT-1 rather than AAT-2. Northern blot analysis showed that the aat-1 clone hybridized to a 1.6 kb transcript present in alfalfa leaves, roots and nodules. The relative concentrations of aat-1 mRNA in these tissues were 1:2:5, respectively. Thus, transcription of aat-1 appears to be induced during nodule development. Southern blot analysis suggested that AAT-1 in alfalfa is encoded by either a single-copy gene or a small, multigene family.
Mol Gen Genet 1991 Dec
PMID:Isolation and analysis of a cDNA clone that encodes an alfalfa (Medicago sativa) aspartate aminotransferase. 175 49

Pyridoxal 5'-phosphate is a coenzyme for a number of enzymes which catalyse reactions at C alpha of amino acid substrates including transaminases, decarboxylases and serine hydroxymethyltransferase. Using the X-ray coordinates for a transaminase, aspartate aminotransferase, and the results of stereochemical and mechanistic studies for decarboxylases and serine hydroxymethyltransferase, an active-site structure for the decarboxylase group is constructed. The structure of the active-site is further refined through active-site pyridoxyllysine peptide sequence comparison and a 3-D catalytic mechanism for the L-alpha-amino acid decarboxylases is proposed. The chemistry of serine hydroxymethyltransferase is re-examined in the light of the proposed decarboxylase mechanism.
Experientia 1991 Dec 01
PMID:A comparison of pyridoxal 5'-phosphate dependent decarboxylase and transaminase enzymes at a molecular level. 176 22

The epidemiological, clinical and clinical pathological findings in 20 cattle and 4 sheep from 15 outbreaks of poultry litter toxicity in South Africa over the past 6 years are documented. In 6 outbreaks, the litter emanated from batteries where maduramicin had been incorporated into rations of broilers. According to circumstantial evidence the litter involved in the 9 other outbreaks was also derived from broilers which had been fed on rations containing an ionophore. The litter was fed ad libitum to the affected stock or constituted 30-80% by volume of their rations. The principal sign manifested was sudden mortality of up to 70% of the herd or flock, usually within 20-40 days of commencement of feeding of poultry litter. A few cattle developed signs of congestive heart failure, and stiffness was commonly seen in sheep. In a dosing trial with poultry litter involving 1 steer and 6 sheep, the steer and a sheep died suddenly and a second sheep was destroyed in extremis. Tachycardia and/or cardiac arrythmia were recorded in 5 sheep, and the activity of aspartate transaminase (AST) and/or lactate dehydrogenase (LD) in the sera of 4 was elevated. Since the cardiac lesions in field cases were similar to those of ionophore poisoning and broiler rations containing maduramicin was a common factor in several outbreaks, toxic litter from some of these outbreaks were tested for the presence of this compound. Analysis by high performance liquid chromatography of litter from 2 specimens of outbreaks revealed that they contained 2.5 ppm and 6.1 ppm maduramicin.(ABSTRACT TRUNCATED AT 250 WORDS)
Onderstepoort J Vet Res 1991 Dec
PMID:Cardiomyopathy of ruminants induced by the litter of poultry fed on rations containing the ionophore antibiotic, maduramicin. I. Epidemiology, clinical signs and clinical pathology. 178 Jan 31

Monoclonal gammopathies can either be benign or more commonly malignant. The commonest disease associated with it is multiple myeloma. Over the seven-year period 1984-1990, two hundred and thirty-four monoclonal gammopathies were seen at the University Hospital, Jamaica. Multiple myeloma was diagnosed in one hundred and fifty-six cases (84 males and 72 females). The diagnoses of most of the others were not known as the samples came from other institutions. Of the patients with myeloma, the most common immunoglobulin type was IgG followed by IgA and then pure light chain disease. Only in about half of the cases where urine was analysed was Bence-Jones protein found. The majority of the cases had abnormal total serum protein, albumin and total globulin concentrations. Most of the cases also were in renal failure. Hypercalcaemia, hyperphosphataemia, elevated alkaline phosphatase, gammaglutamyl transferase and aspartate aminotransferase occurred in about one-third of them. These results were not much different from those reported in other countries.
West Indian Med J 1991 Dec
PMID:Biochemical abnormalities in multiple myeloma. 178 96

31P Nuclear magnetic resonance (NMR) spectroscopy and 1H NMR imaging were used to examine the effect of short-term ethanol feeding on the rat testis. Weanling rats were pair-fed for 10 weeks either on ethanol containing liquid diet (36% ethanol of total calories) or a diet in which dextrimaltose was isocalorically substituted for the ethanol of the alcohol-containing diet. In vivo 31P NMR of the testes was used to determine the intratesticular pH and the relative concentrations of various phosphorus-containing metabolites. The integrity of the blood-testes barrier was evaluated using 1H NMR imaging following a gadolinium diethylene tetramine pentaacetic acid derivative (Gd-DTPA) administration as a vascular contrast agent. After the completion of NMR studies, the testis and the liver were freeze-clamped to allow for the assay of their adenosine-5'-triphosphate (ATP) contents. Serum was assayed for its content of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alcohol and testosterone. Ethanol feeding resulted in the following: (a) a reduction in the body weight (p less than 0.05), (b) a reduction in the testicular phosphodiesters (PDE) PDE/ATP ratio (p less than 0.05), (c) an increased change in the testis image intensity difference between pre- and post-iv Gd-DTPA images, (c) a reduction in the testicular and hepatic content of ATP, and (d) increased serum levels of AST and ALT.(ABSTRACT TRUNCATED AT 250 WORDS)
Alcohol Clin Exp Res 1991 Dec
PMID:Effect of short-term ethanol feeding on rat testes as assessed by 31P NMR spectroscopy, 1H NMR imaging, and biochemical methods. 178 76

We found that 17 out of 60 (28.3 percent) obese, otherwise healthy volunteers had elevated serum alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT) or alkaline phosphatase (AP) at least once in the course of a 12 week clinical trial. ALAT was the most commonly elevated serum aminotransferase occurring in 16 out of the 17 participants. Its range of elevation, as a percentage of the upper limit of normal (ULN) at screening was 102-164 percent (mean +/- s.d.; 127 percent +/- 18.4). Three participants had slight elevations of AP (112 percent, 113 percent, 119 percent of ULN). One participant had a minor elevation of ASAT (107 percent of ULN at screening). Of the 17 participants with elevated aminotransferases and AP, six were randomized to placebo, seven were treated with the low dose and four with the high dose of the new medication. Study participants having elevated enzymes had higher ideal body weight (IBW) than the group with normal values at screening (162 +/- 10 percent IBW, 152 +/- 11 percent IBW respectively), and at week 8 (152 +/- 3 percent IBW, 146 +/- 2 percent respectively) (P less than 0.05). The corresponding body mass index (BMI) values are 36.8 +/- 2.8 for the participants with elevated liver enzymes vs 34.2 +/- 2.6 (P less than 0.001) for the participants with normal values at screening and 34.9 +/- 3.1 and 32.8 +/- 2.8 (P = 0.02) respectively at week 8. Males (46 percent) were more likely than females (21 percent) to have elevated aminotransferases. We found no evidence for hepatic disease during the study period. Slightly elevated and fluctuating serum aminotransferases and alkaline phosphatase concentrations are a more frequent finding in healthy obese populations than previously established. In studies of anti-obesity agents investigators should broaden the entry criteria since elevated aminotransferase levels rarely interfere with the safe conduct of clinical trials in obesity.
Int J Obes 1991 Dec
PMID:Elevated serum liver enzymes in obesity: a dilemma during clinical trials. 179 21

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.
Eur J Clin Chem Clin Biochem 1991 Dec
PMID:Comparison of clinical chemical variables in blood plasma and serum of horses. 179 11

The effects of in vitro treatment with ammonium chloride, hepatic encephalopathy (HE) due to thioacetamide (TAA) induced liver failure and chronic hyperammonemia produced by i.p. administration of ammonium acetate on the activity of the two malate-aspartate shuttle enzymes: aspartate aminotransferase (AAT), malate dehydrogenase (MDH), and on the pyruvate carboxylase (PC) activity were examined in synaptic and nonsynaptic mitochondria from rat brain. With regard to the shuttle enzymes the response to ammonium ions in vitro (3mM NH4Cl) was observed in nonsynaptic mitochondria only, and was manifested by a 27% decrease of AAT activity and a 16% decrease in MDH activity. By contrast, both in vivo conditions primarily affected the synaptic mitochondrial enzymes: TAA-induced HE produced a 26% decrease of synaptic mitochondrial AAT and a 50% decrease of synaptic mitochondrial MDH. Hyperammonemia inhibited synaptic mitochondrial AAT by 30% and synaptic mitochondrial MDH by 45%. HE produced no effect at all in nonsynaptic mitochondria while hyperammonemia produced a 30% increase in the AAT activity, but no changes in MDH. All the experimental conditions affected the nonsynaptic mitochondria PC: ammonium chloride in vitro produced a 20% decrease, TAA-induced HE--a 30% decrease, whereas hyperammonemia inhibited the enzyme by 53%. The PC activity in synaptic mitochondria was very low (about 2% of that measured in nonsynaptic mitochondria), which is consistent with the primarily astrocytic localization of the enzyme.
Metab Brain Dis 1991 Dec
PMID:Aspartate aminotransferase, malate dehydrogenase, and pyruvate carboxylase activities in rat cerebral synaptic and nonsynaptic mitochondria: effects of in vitro treatment with ammonia, hyperammonemia and hepatic encephalopathy. 181 92


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