Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transaminase B (branched-chain amino acid aminotransferase, EC 2.6.1.42), the ilvE gene product, was purified to apparent homogeneity from an Escherichia coli K-12 strain which carries the ilvE gene both on the host chromosome and on a plasmid. The oligomeric structure of the enzyme, as determined by analytical ultracentrifugation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was confirmed to be that of a hexamer with a molecular weight of about 182,000 and apparently identical subunits. Cross-linking with dimethylsuberimidate yielded trimers, dimers, and monomers, but essentially no species of higher molecular weight. These results are consistent with a double-trimer arrangement of the subunits in native enzyme. The amino-terminal sequence was found to be: Gly Thr Lys Lys Ala Asp Tyr Ile (Trp) Phe Asn Gly (Thr) (Met) Val. Purified transaminase B catalyzed transamination between alpha-ketoglutarate and l-isoleucine, l-leucine, l-valine, and, to a lesser extent, l-phenylalanine and l-tyrosine, the latter reacting very sluggishly. The enzyme was free of aspartate transaminase and of transaminase C. The apparent K(m) values for the branched-chain alpha-ketoacids were smaller than those for the corresponding amino acids. The lowest K(m) was recorded for dl-alpha-keto-beta-methyl-n-valerate, and the highest was recorded for l-valine. The ratio of the valine- and isoleucine-alpha-ketoglutarate activities did not change significantly during purification, and both activities were quantitatively removed from crude extract by antibody raised against purified transaminase B. These observations argue against the existence of a separate valine-alpha-ketoglutarate transaminase. Anti-E. coli transaminase B antibody cross-reacted with crude extract from Salmonella typhimurium, but not with extract obtained from Pseudomonas aeruginosa.
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PMID:Transaminase B from Escherichia coli: quaternary structure, amino-terminal sequence, substrate specificity, and absence of a separate valine-alpha-ketoglutarate activity. 37 64

Incubation of rat brain 4-aminobutyrate aminotransferase with 4-amino-hex-5-enoic acid, a substrate analog of 4-aminobutyric acid, results in a time-dependent irreversible loss of enzymatic activity. In the presence of 0.1 mM inhibitor the half-life of the inactivation process is approximately 6 min. Low concentrations of L-glutamic acid or 4-aminobutyric acid protect against this inactivation, while 2-oxoglutarate prevents this protection, suggesting that only the pyridoxal form of the enzyme is susceptible to inhibition by 4-amino-hex-5-enoic acid. The irreversible inhibition of mammalian 4-aminobutyrate aminotransferase by 4-amino-hex-5-enoic acid is selective. There is no inhibition of this enzyme from Pseudomonas fluorescens with the inhibitor at mM concentrations. Even at 10 mM there is no irreversible inhibition of mammalian glutamate decarboxylase or of aspartate aminotransferase, while alanine aminotransferase is inhibited over 500 times more slowly than rat brain 4-aminobutyrate transaminase.
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PMID:4-amino-hex-5-enoic acid, a selective catalytic inhibitor of 4-aminobutyric-acid aminotransferase in mammalian brain. 85 82

The effect of the pyoverdin Pf (an iron chelating agent isolated and purified from Pseudomonas fluorescens CCM 2798) was studied on iron overloaded rat hepatocyte cultures. Iron overload was obtained by addition of 5-80 microM ferric nitrilotriacetate to the culture medium. Twenty-four hours after iron treatment, a significant increase in aspartate aminotransferase and lactate dehydrogenase in the culture medium was observed. This corresponded to intracellular decrease in the activity of these two enzymes and correlated with a decrease in albumin secretion and an increase in total free malondialdehyde production. The iron toxicity was inhibited by desferrioxamine B. Pyoverdin Pf added to the hepatocyte cultures served as an effective agent to prevent iron toxicity induced in overload. The observed effect of the pyoverdin Pf was as potent as that of desferrioxamine B.
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PMID:Inhibition of iron overload toxicity in rat hepatocyte cultures by pyoverdin Pf, the siderophore of Pseudomonas fluorescens. 156 81

Genomic DNA size was measured in three strains of Pseudomonas aeruginosa, ATCC 29260 (exotoxin A), ATCC 33467 (type I smooth) and ATCC 33468 (type 2 mucoid) by transverse alternating field electrophoresis of restriction fragments. Because of the high (67%) G + C content of Pseudomonas aeruginosa, restriction enzymes that recognize sequences with at least 4 AT base pairs were expected to be rare cutters. Eight enzymes produced fragments greater than 200 kb in size: Dral (TTT/AAA), Asnl (ATT/AAT), Hpal (GTT/AAC), AfIII (C/TTAAG), Xbal (T/CTAGA), Spel (A/CTAGT), Sspl (AAT/ATT) and Ndel (CA/TATG). All eight enzymes recognized one of three rare tetranucleotide sequences, TTAA, CTAG or ATAT. Pseudomonas aeruginosa strain 29260 has a genomic DNA size of 5573 kb. Strains 33467 and 33468 have identical restriction patterns and a possible deletion with a genomic size of 5407 kb.
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PMID:Determination of genome size of Pseudomonas aeruginosa by PFGE: analysis of restriction fragments. 197 59

The three-dimensional structure of omega-amino acid:pyruvate aminotransferase from Pseudomonas sp. F-126, an isologous alpha 4 tetramer containing pyridoxal 5'-phosphate (PLP) as a cofactor, has been determined at 2.0 A resolution. The diffraction data were collected with a newly developed Weissenberg camera with a Fuji Imaging Plate, using synchrotron radiation. The mean figure-of-merit was 0.57. The subunit is rich in secondary structure and comprises two domains. PLP is located in the large domain. The high homology in the secondary structure between this enzyme and aspartate aminotransferase strongly indicates that these two types of enzymes have evolved from a common ancestor.
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PMID:Crystal structure analysis of omega-amino acid:pyruvate aminotransferase with a newly developed Weissenberg camera and an imaging plate using synchrotron radiation. 250 Apr 26

DL-(1-Amino-2-propenyl)phosphonic acid was synthesized through the sequential oxidation, sulfoxide elimination, and deprotection of diphenyl [1-[(benzyloxycarbonyl)amino]-3-(phenylthio)propyl] phosphonate. This analogue of vinylglycine is a strong inhibitor of the alanine racemases from Pseudomonas aeruginosa and Streptococcus faecalis and of the D-Ala:D-Ala ligase from this latter species. This molecule is ineffective against the whole bacterial cells. Unlike vinylglycine, this unsaturated phosphonate does not inhibit the following mammalian enzymes: aspartate aminotransferase, alanine aminotransferase, D-amino acid oxidase, which indicates its specificity. Thus, its incorporation in a peptide structure could induce interesting antimicrobial properties.
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PMID:(1-Amino-2-propenyl) phosphonic acid, an inhibitor of alanine racemase and D-alanine:D-alanine ligase. 287 Jan 90

Aztreonam was used successfully in 17 of 17 patients with orthopedic infections due to gram-negative bacilli (11, osteomyelitis; six, septic arthritis). Duration of treatment ranged from 14 to 55 days, and the period of follow-up was four to 18 months. Causative organisms included Pseudomonas aeruginosa, Serratia marcescens, Enterobacter gergoviae, Citrobacter diversus, Proteus mirabilis, and Enterobacter aerogenes. Aztreonam was well tolerated. The only definite reactions attributable to aztreonam were asymptomatic increases in serum aspartate aminotransferase (SGOT) and serum alanine aminotransferase (SGPT) in four patients; none of these reactions interfered with completion of therapy. Adverse reactions that were possibly attributable to aztreonam included rash (two patients), diarrhea (one patient), and leukopenia (one patient). All of these patients were receiving antibiotics active against gram-positive organisms in mixed infections in addition to aztreonam. Aztreonam is a promising new monobactam without significant toxicity. It has good activity against gram-negative aerobic bacteria, including P. aeruginosa, and is effective in the treatment of serious infections due to gram-negative aerobes.
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PMID:Aztreonam in the treatment of bone and joint infections caused by gram-negative bacilli. 293 86

The effect of various proteases (trypsin, chymotrypsin, subtilisin, protease 401, and thermolysin) on the mitochondrial isoenzyme (m-AST) and cytoplasmic isoenzyme (c-AST) of human and swine aspartate aminotransferase (AST;EC 2.6.1.1) was evaluated. All procedures including the reaction with proteases and the subsequent determination of the AST activity were carried out in an automatic analyzer. The mammalian c-AST was efficiently inactivated by chymotrypsin, subtilisin and protease 401 while m-AST activity decreased very slowly with these proteases. Thermolysin and trypsin showed much less effect on c-AST activity. Especially, chymotrypsin at concentrations of 0.5-1.0 g/L inactivated human c-AST almost completely but showed no detectable inactivating effect on m-AST. Thus chymotrypsin appears to be the most suitable protease for the differential determination of AST isoenzymes in human serum. Further studies on the effects of proteases with AST from other species showed that Escherichia coli AST resembled mammalian m-AST while Pseudomonas AST resembled c-AST.
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PMID:Determination of human aspartate aminotransferase isoenzymes by their differential sensitivity to proteases. 306 46

An open clinical study of ofloxacin in respiratory tract infections was conducted with patients receiving daily doses of ofloxacin 300 mg, 400 mg or 600 mg. The duration of treatment was 6 to 14 days for 70% of the patients. Ofloxacin was effective in 668 of 828 patients analysed (80.7%). Of 293 patients with upper respiratory infections, the efficacy rate was 85.3%. In 535 cases with lower respiratory infections, ofloxacin was effective in 78.1%. It is noteworthy that a 70% efficacy rate was obtained in 80 cases with intractable chronic diffuse panbronchiolitis primarily associated with Pseudomonas aeruginosa. There was no difference in the efficacy rate among various daily doses or severity of infections. In lower respiratory infections the bacterial eradication rate was 80.9% for Gram-positive aerobes (including 80% for Staphylococcus aureus and 76.5% for Streptococcus pneumoniae) and 72.1% for Gram-negative aerobes (including 92.6% for Klebsiella pneumoniae, 32.3% for P. aeruginosa and 97.1% for Haemophilus influenzae). Although there were no serious cases, adverse reactions were noted in 46 of 843 patients (5.5%): 38 cases (4.5%) of gastrointestinal tract reactions (nausea, vomiting, heartburn, etc.), 4 cases (0.5%) of hypersensitivity (e.g. eruption) and 19 (2.3%) of central nervous system effects (e.g. dizziness). Abnormal changes in laboratory findings included elevations of AST (1.2%) and ALT (1.5%) and an increase in the eosinophil count (1.7%).
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PMID:Ofloxacin in respiratory tract infection. A review of the results of clinical trials in Japan. 332 61

We evaluated the concept that the vascular entrance of both bacterial and nonbacterial particulate material could lead to hepatic parenchymal cell injury, either due to postphagocytic Kupffer cell activity or the margination of activated leukocytes in the liver. Injection of denatured, collagen-coated particles as well as heat-killed bacteria were used as particulate challenges. Hepatic parenchymal cell injury in vivo during postoperative sepsis was evaluated by plasma aspartate aminotransferase (AST) and ornithine carbamyl transferase (OCT) enzyme levels over 3-72 h. AST and OCT levels elevated following either laparotomy plus cecal ligation (mild sepsis) or laparotomy plus cecal ligation with puncture (severe sepsis), with the peak level at 24 h. In addition, the direct intravenous injection of either nonbacterial foreign particles or heat-killed Pseudomonas aeruginosa into normal rats also produced a dose-dependent elevation of AST and OCT. The plasma level of either AST or OCT actually increased 350-400% after injection of the non-bacterial particles. A similar dose related elevation in enzymes followed the intravenous injection of heat-killed Pseudomonas. To differentiate the potential contribution of activated hepatic Kupffer cells versus activated marginated neutrophils to the in vivo hepatic injury, we determined the release of the hepatic specific enzyme OCT by cultured hepatic parenchymal cells when they were exposed to isolated Kupffer cells or isolated PMNs that were activated by exposure to dead bacteria. Bacteria alone when added to cultured hepatocytes did not induce significant OCT release. In contrast, activated PMNs but not Kupffer cells induced a significant (p less than 0.05) release of OCT from parenchymal cells into the culture media. Thus, in vivo transient hepatic parenchymal cell injury with post-operative sepsis may be mediated by the margination of activated PMNs in the liver.
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PMID:Hepatocyte injury during post-operative sepsis: activated neutrophils as potential mediators. 342 80


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