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 ybdL gene of Escherichia coli codes for a protein of unknown function. Sequence analysis showed moderate homology to several vitamin B(6) dependent enzymes, suggesting that it may bind pyridoxal-5'-phosphate. The structure analysis of YbdL to 2.35 A resolution by protein crystallography verifies that it is a PLP dependent enzyme of fold type I, the typical aspartate aminotransferase fold. The active site contains a bound pyridoxal-5'-phosphate, covalently attached to the conserved active site lysine residue Lys236. The pattern of conserved amino acids in the putative substrate binding pocket of the enzyme reveals that it is most closely related to a hyperthermophilic aromatic residue aminotransferase from the archeon Pyrococcus horikoshii. Activity tests with 10 amino acids as amino-donors reveal, however, a preference for Met, followed by His and Phe, results which can be rationalized by modelization studies.
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PMID:Crystal structure and reactivity of YbdL from Escherichia coli identify a methionine aminotransferase function. 1528 32

Fenofibrate-induced acute or chronic hepatitis is rare, and only 11 reports from French, Italian or Spanish literature have been published up to date. We report a case of fenofibrate-induced acute cholestatic hepatitis. To the best of our knowledge, this is the first one reported in Taiwan. A 61-year-old man developed acute cholestatic hepatitis after taking fenofibrate 100 mg tid for 10 days. Laboratory profile on admission showed serum total bilirubin 9.3 mg/dL, direct bilirubin 2.7 mg/dL, alanine aminotransferase 249 IU/L, aspartate aminotransferase 259 IU/L, alkaline phosphatase 259 IU/L, and gamma-glutamyl transpeptidase 1014 IU/L. Pathology proved hepatocanalicular cholestasis in liver. Fenofibrate was discontinued immediately. His clinical manifestations and liver function tests improved gradually and returned to nearly normal in 2 months. We suggest that liver function tests, including total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase, be checked at least 2 weeks after taking the drug and that serum aminotransferase be monitored every 3 months during the first 12 months of therapy. Treatment should be discontinued if alanine aminotransferase values increase by more than 100 IU/L.
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PMID:Fenofibrate-induced acute cholestatic hepatitis. 1535 12

The antimutagenic activity of the methanolic extract of the fruiting bodies of Ganoderma lucidum (Fr.) P. Krast. occurring in South India was investigated. The activity was assayed by Ames Salmonella mutagenicity test using histidine mutants of Salmonella typhimurium tester strains, TA98, TA100 and TA102. The methanolic extract of the mushroom significantly inhibited (P<0.001) the in vitro sodium azide (NaN(3)), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 4-nitro-o-phenylenediamine (NPD), and benzo[a]pyrene (B[a]P) induced his(+) revertants in a dose dependent manner. In vivo antimutagenic activity of extract was also assayed by determining the mutagenicity of the urine of rats administrated with B[a]P as a mutagen. The prior administration of extract markedly inhibited mutagenicity induced by B[a]P. The results indicated that the methanolic extract of Ganoderma lucidum occurring in South India possessed significant antimutagenic activity. The effect of B[a]P on hepatic enzymes, such as serum glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and alkaline phosphtase (ALP), were also evaluated. The extract prevented the increase of SGOT, SGPT, and ALP activities consequent to B[a]P challenge, and enhanced the levels of reduced glutathione (GSH) and activities of glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT). The extract also profoundly inhibited lipid peroxidation induced by B[a]P. The results revealed that Ganoderma lucidum extract restored antioxidant defense and prevented hepatic damage consequent to the challenge by B[a]P.
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PMID:Antimutagenic activity of methanolic extract of Ganoderma lucidum and its effect on hepatic damage caused by benzo[a]pyrene. 1671 54

Parenteral nutrition-associated cholestasis (PNAC) is a complication not uncommon in the pediatric population. In severe cases, patients require a liver transplant. To our knowledge, we report the only case of PNAC with end-stage liver failure in a child with short bowel syndrome that resolved with a change in caretaker. Until his care was transferred from his abusive parents, he was frequently admitted for infection and sepsis. His liver function vastly improved from aspartate aminotransferase (AST) 3139 units/L, conjugated bilirubin 25.9 mg/dL to AST 47 units/L, direct bilirubin 0.3 mg/dL under the care of his attentive foster mother, and a liver transplant was no longer necessary. Bacterial infection and sepsis are risk factors correlated with patients with PNAC requiring liver transplant. Prevention of infection by a good caregiver may be a means to reduce the incidence of PNAC.
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PMID:Parenteral nutrition-associated cholestasis related to parental care. 1677 46

L-colitose is a 3,6-dideoxysugar found in the O-antigens of some Gram-negative bacteria such as Escherichia coli and in marine bacteria such as Pseudoalteromonas tetraodonis. The focus of this investigation, GDP-4-keto-6-deoxy-D-mannose-3-dehydratase, catalyzes the third step in colitose production, which is the removal of the hydroxyl group at C3' of GDP-4-keto-6-deoxymannose. It is an especially intriguing PLP-dependent enzyme in that it acts as both a transaminase and a dehydratase. Here we present the first X-ray structure of this enzyme isolated from E. coli Strain 5a, type O55:H7. The two subunits of the protein form a tight dimer with a buried surface area of approximately 5000 A2. This is a characteristic feature of the aspartate aminotransferase superfamily. Although the PLP-binding pocket is formed primarily by one subunit, there is a loop, delineated by Phe 240 to Glu 253 in the second subunit, that completes the active site architecture. The hydrated form of PLP was observed in one of the enzyme/cofactor complexes described here. Amino acid residues involved in anchoring the cofactor to the protein include Gly 56, Ser 57, Asp 159, Glu 162, and Ser 183 from one subunit and Asn 248 from the second monomer. In the second enzyme/cofactor complex reported, a glutamate ketimine intermediate was found trapped in the active site. Taken together, these two structures, along with previously reported biochemical data, support the role of His 188 as the active site base required for catalysis.
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PMID:The structure of GDP-4-keto-6-deoxy-D-mannose-3-dehydratase: a unique coenzyme B6-dependent enzyme. 1694 43

Chemoprevention is an important alternative approach to control cancer. Chemical substances with multiple inhibitory properties would be a welcome addition to the class of chemopreventive drugs. In this study, we investigated the antioxidant, anti-inflammatory, antimutagenic and cancer preventive activities of aqueous extract of a macrofungus Phellinus rimosus (Berk) Pilat. The extract exhibited superoxide anion (O2-), hydroxyl radical (*OH), nitric oxide (NO*) scavenging and lipid peroxidation inhibiting activities. The inhibitory concentrations required by the extract to scavenge 50% (IC50) of the superoxide anion, hydroxyl radical and nitric oxide generated were 126 +/- 5.1, 71 +/- 4.7 and 31 +/- 4.5 microg/ml respectively. The concentration required to inhibit 50% of Fe2+ induced lipid peroxidation in rat liver homogenate was 318 +/- 2.4 microg/ml. The extract showed significant (P<0.05) anti-inflammatory activity in a dose dependent manner. Extract (100 mg/kg body wt, p.o) inhibited 44.5, 45.4 and 47% carrageenen, dextran and formalin induced inflammations respectively. The antimutagenic activity was determined by the Ames' Salmonella mutagenecity assay using histidine mutant Salmonella typhimurium strains. The extract at concentration of 5 mg/plate showed antimutagenecity against benzo[a]pyrene (B[a]P) and 4-nitro-o-pheneylenediamine (NPDA) induced mutations of TA98 and TA100 respectively. Anticarcinogenic activity was evaluated using N-nitrosodiethylamine (NDEA) induced hepatocellular carcinoma (HCC) in rats. Serum gamma glutamyl transpeptidase (GGT), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) activities and lipid peroxidation level (MDA) were elevated significantly (P<0.05) in the NDEA alone treated group of animals. Treatment of the extract (25 and 50 mg/kg body wt, p.o.) prior to the NDEA administration decreased the serum GGT, GOT, GPT and ALP activities and MDA level in a dose dependent manner. The NDEA alone treated animals showed altered serum albumin/globulin ratio (A:G ratio), hyperfibrinogenaemia, increased hepatic glutathione S-transferase (GST) activity, glutathione-peroxidsae (GPx) activity and reduced glutathione (GSH) level compared to the extract plus NDEA treated group. The extract also inhibited in vitro aniline hydroxylase (AH) activity of rat liver induced by phenobarbitone in a dose dependent manner. The results, thus suggest the significant chemopreventive properties of the aqueous extract of the Phellinus rimosus against NDEA induced hepatocellular carcinoma by its antioxidant, anti-inflammatory and antimutagenic activities.
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PMID:Chemopreventive activity of a macrofungus Phellinus rimosus against N-nitrosodiethylamine induced hepatocellular carcinoma in rat. 1702 71

Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
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PMID:Crystal structure of Homo sapiens kynureninase. 1730 Jan 76

Rhabdomyolysis induced acute renal failure (ARF) is relatively rare in children. We report an 8-year-old boy with McArdle disease and rhabdomyolysis induced ARF after heavy muscle work. Physical examination revealed generalized tenderness on his extremities. Laboratory examinations showed acute renal failure due to myoglobinuria and revealed alanine transaminase 428 U/l, aspartate transaminase 1,400 U/l, blood urea nitrogen 119 mg/dl, creatinin 3.6 mg/dl, uric acid 13 mg/dl, and serum creatinine kinase (CK) 33,766 U/l. Hemodialysis was carried out for ARF. His clinical and laboratory findings improved and became normal in 2 weeks. Enzymatic analysis of the muscle biopsy showed a phosphorylase A level of 129 nmol/s/mg protein (normal: 200-600) and a phosphorylase A+B level of 385 nmol/s/mg protein (normal: 500-1500), which was compatible with glycogenosis type V. As McArdle disease rarely becomes symptomatic and ARF secondary to this condition is very rare, our case represents a rare clinical presentation.
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PMID:Acute renal failure due to rhabdomyolysis in a child with McArdle disease. 1789 90

Alleviative effects of histidine and carnosine in mice against ethanol-induced oxidative and inflammatory was examined. After chronic alcoholic liver injury was induced, histidine and carnosine at 0.5, 1, 2g/L were added to the drinking water for 3 weeks. Results showed that the post-intake of histidine or carnosine markedly decreased alanine aminotransferase and aspartate aminotransferase activities (P<0.05). Ethanol treatment increased malondialdehyde (MDA) level, decreased glutathione (GSH) content and catalase and glutathione peroxidase (GPX) activities, and increased cytochrome P450 2E1 (CYP2E1) activity in liver (P<0.05). The post-intake of histidine and carnosine significantly decreased MDA formations, increased GSH content, enhanced catalase and GPX activities, and suppressed CYP2E1 activity (P<0.05), in which the effects on catalase and CYP2E1 activities were dose-dependent (P<0.05). Ethanol treatment elevated hepatic levels of c-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) (P<0.05), the post-intake of histidine and carnosine significantly and dose-dependently diminished the release of CRP, IL-6, and TNF-alpha (P<0.05). Ethanol treatment caused down-regulation in both catalase and GPX mRNA expression, and up-regulated both IL-6 and TNF-alpha mRNA expression (P<0.05). Histidine and carnosine post-treatments significantly and dose-dependently upregulated catalase mRNA, and down-regulated mRNA expression of IL-6 and TNF-alpha (P<0.05). Based on the observed anti-oxidative and anti-inflammatory effects, the supplement of histidine or carnosine might be helpful for the treatment of chronic alcoholic liver injury.
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PMID:Beneficial effects of histidine and carnosine on ethanol-induced chronic liver injury. 1822 27

Liver, pancreas, and kidney allografts preserved in histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) solutions have similar clinical outcomes. This study compares HTK and UW in a large number of standard criteria donor (SCD) and extended criteria donor (ECD) livers at a single center over 5 years. All adult, cadaveric liver and liver-kidney transplants performed between July 1, 2001 and June 30, 2006 were reviewed (n = 698). There were 435 livers (62%) categorized as ECD for severe physiologic stress and 70 (10%) because of old age. Recipient outcomes included perioperative death or graft loss and overall survival. Liver enzymes were analyzed for the first month post-transplant. Biliary complications were assessed through chart review. Overall, 371 donor livers were preserved in HTK (53%), and 327 were preserved in UW (47%). There were no statistically significant differences in any of the primary outcome measures comparing HTK and UW. The HTK group overall had a higher day 1 median aspartate aminotransferase and alanine aminotransferase, but the two groups were similar in function thereafter. HTK was superior to UW in protection against biliary complications. Kaplan-Meier graft survival curves failed to demonstrate a significant difference in SCD or ECD livers. In conclusion, HTK and UW are not clinically distinguishable in this large sample of liver transplants, although HTK may be protective against biliary complications when compared to UW. These findings persisted for both SCD and ECD livers. Given the lower cost per donor for HTK, this preservation solution may be preferable for general use.
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PMID:Comparison of histidine-tryptophan-ketoglutarate solution and University of Wisconsin solution in extended criteria liver donors. 1830 80


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