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)

Blood samples were collected from 158 Holstein-Friesian cows and analysed for aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase and ornithine carabamoyltransferase activities and glucose, total bilirubin, triglyceride, cholesterol-ester and non-esterified fatty acids concentrations. Ultrasonography of the liver was performed, and hepatic ultrasonograms were evaluated subjectively or analysed digitally, and liver samples were examined histopathologically. The diagnostic rates for the different tests were compared. Of the 158 animals, 117 had a normal liver and 41 had fatty infiltration of the liver. For diagnosis of fatty infiltration, digital analysis had the highest sensitivity, specificity, accuracy, and positive and negative predictive values, followed by ultrasonography.
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PMID:Comparative evaluation of fatty infiltration of the liver in dairy cattle by using blood and serum analysis, ultrasonography, and digital analysis. 761 May 50

Ornithine decarboxylases from Trypanosoma brucei, mouse, and Leishmania donovani share strict specificity for three basic amino acids, ornithine, lysine, and arginine. To identify residues involved in this substrate specificity and/or in the reaction chemistry, six conserved acidic resides (Asp-88, Glu-94, Asp-233, Glu-274, Asp-361, and Asp-364) were mutated to alanine in the T. brucei enzyme. Each mutation causes a substantial loss in enzyme efficiency. Most notably, mutation of Asp-361 increases the Km for ornithine by 2000-fold, with little effect on kcat, suggesting that this residue is an important substrate binding determinant. Mutation of the only strictly conserved acidic residue, Glu-274, decreases kcat 50-fold; however, substitution of N-methylpyridoxal-5'-phosphate for pyridoxal-5'-phosphate as the cofactor in the reaction restores the kcat of E274A to wild-type levels. These data demonstrate that Glu-274 interacts with the protonated pyridine nitrogen of the cofactor to enhance the electron withdrawing capability of the ring, analogous to Asp-222 in aspartate aminotransferase (Onuffer, J. J., and Kirsch, J. F. (1994) Protein Eng. 7, 413-424). Eukaryotic ornithine decarboxylase is a homodimer with two shared active sites. Residues 88, 94, 233, and 274 are contributed to each active site from the same subunit as Lys-69, while residues 361 and 364 are part of the Cys-360 subunit.
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PMID:Acidic residues important for substrate binding and cofactor reactivity in eukaryotic ornithine decarboxylase identified by alanine scanning mutagenesis. 774 28

An assay procedure for ornithine carbamoyl transferase (OCT), which is known to be a liver-specific enzyme, was modified to be adaptable to bovine serum. The concentration of carbamoyl phosphate and the pH of the reaction reagent solution shifted to 60 mM and 7.2, respectively. These modifications contributed to the augmentation of assay sensitivity. The day-to-day reproducibility was 7.9% (coefficient variation) for serum with high OCT activity and 14.8% for normal bovine serum. The activity was stable for 3-4 months by the storage at -20 degrees C and at least 6 months at -80 degrees C. The OCT activity and other biochemical components including aspartate aminotransferase and gamma glutamyl transpeptidase were measured in sera from 164 dairy or raising cows reared at 7 farms. The normal level of OCT activity in sera from these cows ranged from 9.2 to 25.1 U/l (mean +/- 2SD). By comparison between the farms, the highest mean value of OCT activity was found in a farm where cows were suspected to have some kind of latent liver disease from the data of other biochemical parameters. We conclude that the OCT activity is a very useful diagnostic indicator of liver disease in cattle.
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PMID:Assay of ornithine carbamoyl transferase activity: modification for application to bovine serum. 791 34

Nitric oxide (NO) and prostaglandins (PG) both possess the ability to induce vasodilatation and prevent the aggregation of platelets. The synthesis of these substances is increased following in vivo lipopolysaccharide (LPS) infusion, but their function during sepsis is incompletely understood. We studied the role of NO and PG in a murine model of chronic hepatic inflammation (Corynebacterium parvum injection), which is known to progress to sudden hepatic necrosis after LPS injection. NO synthesis, which is induced in hepatocytes by C. parvum treatment and in nonparenchymal cells by LPS treatment, was inhibited using NG-monomethyl-L-arginine (L-NMMA). High-dose aspirin (ASA) was used to block PG synthesis. Treatment with L-NMMA or ASA alone, in the absence of LPS, resulted in no increase in hepatic injury. C. parvum-treated mice that received both L-NMMA and ASA without LPS developed marked hepatic damage as reflected by increased hepatocellular enzyme release (aspartate aminotransferase and L-ornithine carbamoyl-transferase). Marked hepatic damage was seen after LPS administration, and ASA pretreatment alone had no effect on the LPS-induced hepatic injury, whereas L-NMMA markedly increased the hepatic damage. The combination of L-NMMA and ASA after LPS resulted in the greatest hepatocellular enzyme release, characterized histologically by intravascular thrombosis with diffuse infarction and necrosis. Simultaneous treatment with either PGI2 or L-arginine partially prevented this injury. These data demonstrate that NO and PG function synergistically to maintain hepatocellular integrity; thus increased synthesis of these mediators protects the liver from the pathophysiological effects of LPS in this model.
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PMID:Nitric oxide and prostaglandins interact to prevent hepatic damage during murine endotoxemia. 802 33

A total of 150 amino acid sequences of vitamin B6-dependent enzymes are known to date, the largest contingent being furnished by the aminotransferases with 51 sequences of 14 different enzymes. All aminotransferase sequences were aligned by using algorithms for sequence comparison, hydropathy patterns and secondary structure predictions. The aminotransferases could be divided into four subgroups on the basis of their mutual structural relatedness. Subgroup I comprises aspartate, alanine, tyrosine, histidinol-phosphate, and phenylalanine aminotransferases; subgroup II acetylornithine, ornithine, omega-amino acid, 4-aminobutyrate and diaminopelargonate aminotransferases; subgroup III D-alanine and branched-chain amino acid aminotransferases, and subgroup IV serine and phosphoserine aminotransferases. (N-1) Profile analysis, a more stringent application of profile analysis [Gribskov, M., McLachlan, A. D. and Eisenberg, D. (1987) Proc. Natl Acad. Sci. USA 84, 4355-4358], established the homology among the enzymes of each subgroup as well as among all subgroups except subgroup III. However, similarity of active-site segments and the hydropathy patterns around invariant residues suggest that subgroup III, though most distantly related, might also be homologous with the other aminotransferases. On the basis of the comprehensive alignment, a new numbering of amino acid residues applicable to aminotransferases (AT) in general is proposed. In the multiply aligned sequences, only four out of a total of about 400 amino acid residues proved invariant in all 51 sequences, i.e. Gly(314AT)197, Asp/Glu(340AT)222, Lys(385AT)258 and Arg(562AT)386, the number not in parentheses corresponding to the structure of porcine cytosolic aspartate aminotransferase. Apparently, the aminotransferases constitute a group of homologous proteins which diverged into subgroups and, with some exceptions, into substrate-specific individual enzymes already in the universal ancestor cell.
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PMID:Aminotransferases: demonstration of homology and division into evolutionary subgroups. 851 4

Chronic occupational exposure to organophosphorus and carbamate-type pesticides significantly inhibits acetylcholinesterase activity and causes morbidity. This study on mice was designed to evaluate their amino profile and to identify signs of hepatic dysfunction following their chronic exposure to mixtures of organophosphorus pesticides. Laboratory mice were exposed to a formulated mixture of the six organophosphorus pesticides (Dimethoate, Chlorpyrifos, Profenofos, Pirimiphos methyl, Triazophos and Dimethoate) most commonly used in agriculture in this region of the Middle East. Doses (10% of LD50 of the mixture) were given once a week by gavage in corn oil for 7 weeks; the control group was given only corn oil. At the end of the exposure period, mice were culled and blood samples were collected to determine erythrocyte acetylcholinesterase activity, biochemical markers of liver function and concentrations of serum amino acids. Erythrocyte acetylcholinesterase activity and total serum proteins decreased significantly in the exposed group. Serum concentrations of alanine aminotransferase and aspartate aminotransferase, alanine, glutamic acid, glycine, isoleucine, leucine, methionine, ornithine, proline, serine, threonine and valine were significantly increased in the exposed mice, while serum levels of cystine were decreased significantly. There were also non-significant increases in serum alkaline phosphatase, gama-glutamyl transpeptidase and some of the other amino acids. Chronic exposure to mixtures of organophosphorus pesticides is associated with decreased acetylcholinesterase activity, hepatic dysfunction and disturbance of amino acids profile. Biochemical indices of hepatocellular injury and disturbed amino acid metabolism may be of value as markers of chronic exposure to such pesticides.
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PMID:Hepatic injury and disturbed amino acid metabolism in mice following prolonged exposure to organophosphorus pesticides. 1002 66

The effect of kolaviron, a mixture of Garcinia biflavonoid 1 (GB1), Garcinia biflavonoid 2 (GB2) and kolaflavanone, used in the treatment of various ailments in southern Nigeria on hepatotoxicity and lipid peroxidation induced by 2-acetylaminofluorene (2-AAF) in rats was investigated. The ability of butylated hydroxyanisole (BHA) to attenuate the toxic effect of 2-AAF was also examined. Kolaviron administered orally to rats at a dose of 100mg/kg body weight twice a day for 1 week before challenge with 2-AAF (200mg/kg feed) and continuously for 3 weeks at a single dose of 200mg/kg body weight reversed the 2-AAF-mediated decrease in final body weight and relative organ weights, especially the liver. BHA was administered at a dose of 7.5g/kg feed to the animals for 4 weeks. The extract decreased significantly the 2-AAF-mediated increase in the activity of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase and ornithine carbamyl transferase by 58%, 62%, 60% and 67%, respectively. BHA elicited respectively 55%, 63%, 57% and 65% reduction in the 2-AAF induced-increase in the activities of these enzymes. Histological examination of the liver slices correlated with the changes in serum enzyme alterations. Similarly, kolaviron decreased the 2-AAF reduction of 5'-nucleotidase and glucose-6-phosphatase activities by 63% and 60%, respectively while BHA elicited 59% and 61% decrease in the activities of these enzymes. Simultaneous administration of kolaviron with 2-AAF inhibited microsomal lipid peroxidation as assessed by the thiobarbituric acid reacting substances (TBARS) formation by 66%. BHA produced a 64% reduction in TBARS formation. In the present study, kolaviron appears to act as an in vivo natural antioxidant and an effective hepatoprotective agent and is as effective as BHA.
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PMID:Chemoprevention of 2-acetylaminofluorene-induced hepatotoxicity and lipid peroxidation in rats by kolaviron--a Garcinia kola seed extract. 1082 5

The mass transfers of O2, glucose, NH3, urea and amino acids across the portal-drained viscera (PDV) and the liver were quantified, by arterio-venous techniques, during the last 4 h of a 100 h infusion of 0 (basal), 150 or 400 mumol NH4HCO3/min into the mesenteric vein of three sheep given 800 g grass pellets/d and arranged in a 3 x 3 Latin-square design. Urea irreversible loss rate (ILR) was also determined by continuous infusion of [14C]urea over the last 52 h of each experimental period. PDV and liver movements of glucose, O2 and amino acids were unaltered by NH4HCO3 administration, although there was an increase in PDV absorption of non-essential amino acids (P = 0.037) and a trend for higher liver O2 consumption and portal appearance of total amino acid-N, glucogenic and non-essential amino acids at the highest level of infusion. PDV extraction of urea-N (P = 0.015) and liver removal of NH3 (P < 0.001), release of urea-N (P = 0.002) and urea ILR (P = 0.001) were all increased by NH4HCO3 infusion. Hepatic urea-N release (y) and NH3 extraction (x) were linearly related (R2 0.89), with the slope of the regression not different from unity, both for estimations based on liver mass transfers (1.16; SE 0.144; P(b) not equal to 1 = 0.31) and [14C]urea (0.97; SE 0.123; P(b) not equal to 1 = 0.84). The study indicates that a sustained 1.5 or 2.4-fold increase in the basal NH3 supply to the liver did not impair glucose or amino acid supply to non-splanchnic tissues; nor were additional N inputs to the ornithine cycle necessary to convert excess NH3 to urea. Half of the extra NH3 removed by the liver was, apparently, utilized by periportal glutamate dehydrogenase and aspartate aminotransferase for sequential glutamate and aspartate synthesis and converted to urea as the 2-amino moiety of aspartate.
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PMID:Influence of hepatic ammonia removal on ureagenesis, amino acid utilization and energy metabolism in the ovine liver. 1088 19

The mechanism of pellagrous changes in skin caused by a deficiency of vitamin B6 was studied in respect to neogenesis of proline in skin collagen and glucose metabolism. In vitamin B6 deficiency the insulin/glucagon coefficient in serum decreased significantly from 3.02 to 2.32, indicating a metabolic change towards gluconeogenesis. A deficiency of vitamin B6 caused a decrease in the levels of vitamin B6-dependent enzymes, such as ornithine aminotransferase, alanine aminotransferase, and aspartate aminotransferase, which also contribute to gluconeogenesis. Because the conversion of ornithine to proline via pyrroline-5-carboxylate was suppressed due to the decrease in ornithine aminotransferase activity, the amount of proline in the skin collagen fraction also decreased significantly in vitamin B6-deficient rats compared with the pair-fed control. These results suggest that the pellagrous lesions in vitamin B6-deficiency are caused by an impaired synthesis of proline from ornithine, which results in the suppression of collagen neogenesis in the skin.
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PMID:Changes of glucose metabolism and skin-collagen neogenesis in vitamin B6 deficiency. 1617 47

The jawless fish, the sea lamprey (Petromyzon marinus), spends part of its life as a burrow-dwelling, suspension-feeding larva (ammocoete) before undergoing a metamorphosis into a free swimming, parasitic juvenile that feeds on the blood of fishes. We predicted that animals in this juvenile, parasitic stage have a great capacity for catabolizing amino acids when large quantities of protein-rich blood are ingested. The sixfold to 20-fold greater ammonia excretion rates (J(Amm)) in postmetamorphic (nonfeeding) and parasitic lampreys compared with ammocoetes suggested that basal rates of amino acid catabolism increased following metamorphosis. This was likely due to a greater basal amino acid catabolizing capacity in which there was a sixfold higher hepatic glutamate dehydrogenase (GDH) activity in parasitic lampreys compared with ammocoetes. Immunoblotting also revealed that GDH quantity was 10-fold and threefold greater in parasitic lampreys than in ammocoetes and upstream migrant lampreys, respectively. Higher hepatic alanine and aspartate aminotransferase activities in the parasitic lampreys also suggested an enhanced amino acid catabolizing capacity in this life stage. In contrast to parasitic lampreys, the twofold larger free amino acid pool in the muscle of upstream migrant lampreys confirmed that this period of natural starvation is accompanied by a prominent proteolysis. Carbamoyl phosphate synthetase III was detected at low levels in the liver of parasitic and upstream migrant lampreys, but there was no evidence of extrahepatic (muscle, intestine) urea production via the ornithine urea cycle. However, detection of arginase activity and high concentrations of arginine in the liver at all life stages examined infers that arginine hydrolysis is an important source of urea. We conclude that metamorphosis is accompanied by a metabolic reorganization that increases the capacity of parasitic sea lampreys to catabolize intermittently large amino acid loads arising from the ingestion of protein rich blood from their prey/hosts. The subsequent generation of energy-rich carbon skeletons can then be oxidized or retained for glycogen and fatty acid synthesis, which are essential fuels for the upstream migratory and spawning phases of the sea lamprey's life cycle.
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PMID:Shifting patterns of nitrogen excretion and amino acid catabolism capacity during the life cycle of the sea lamprey (Petromyzon marinus). 1692 35


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