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)

Sea raven (Hemitripterus americanus) given intraperitoneal implants of coconut oil containing cortisol (50 mg kg-1) and sampled 5 days later had plasma cortisol, glucose and urea concentrations higher than in a sham-implanted group. No differences in plasma ammonia, free amino acid or fatty acid concentrations were apparent between the cortisol- and sham-treated groups. There was no change in hepatic glycogen content, whereas glutamine synthetase, allantoicase, arginase, aspartate aminotransferase, tyrosine aminotransferase, alanine aminotransferase, glutamate dehydrogenase, phosphoenolpyruvate carboxykinase and 3-hydroxyacyl-coenzyme A dehydrogenase activities were higher in the cortisol-treated fish liver compared with the sham-implanted fish. On the basis of these general increases in enzyme activities, our results suggest that cortisol stimulates nitrogen metabolism in the sea raven. Amino acid catabolism may be a major source of substrate for gluconeogenesis and/or oxidation, while fatty acid mobilization may provide the fuel for endogenous use by the liver in cortisol-treated sea raven. These results further support the hypothesis that cortisol plays a role in the regulation of glucose production in stressed fish.
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PMID:Metabolic effects of cortisol treatment in a marine teleost, the sea raven 931 10

Circadian oscillations of liver tyrosine aminotransferase (TAT) tryptophan oxygenase (TO), alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), and glutamate dehydrogenase (GLDH) in temporal pattern of protein input have been investigated. Cosinor analysis of oscillations parameters revealed the glucocorticoid induction of TO activity and protein induction of TAT activity rhythm. ALAT, ASAT, and GLDH activities showed 24 h fluctuations, but the regulation mechanisms remain unclear.
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PMID:Cosinor analysis of circadian oscillations of amino acid catabolizing enzymes in temporal pattern of nutrient input. 955 37

Methionine consumed during the synthesis of polyamines can be recycled in most organisms by a unique pathway wherein the final step is the transaminative conversion of alpha-ketomethiobutyrate to methionine (KMAT activity). In the trypanosomatid Crithidia fasciculata, three separate aminotransferases (KMAT-A, -B, -T) were found to catalyse this activity. All three aminotransferases were found to utilise aromatic amino acids as the amino donor for the KMAT reaction, but KMAT-A functioned optimally with histidine and KMAT-B with arginine as amino donors. KMAT-T was found to operate best with aromatic amino acids and glutamate as amino donors, and was also found to catalyse aspartate aminotransferase and tyrosine aminotransferase activities. Amino acid sequencing of internal peptides from KMAT-T yielded a sequence with very high identity to vertebrate, cytosolic aspartate aminotransferase. As pig heart cytosolic aspartate and alanine aminotransferases were found to be unable to catalyse KMAT activity, the crithidial enzyme appears to be an aspartate aminotransferase with unusual catalytic properties. Inhibition studies on C. fasciculata homogenates showed that carboxymethoxylamine, canaline, and nitrophenylalanine were effective inhibitors of total KMAT activity (63-100% inhibition at 1 mM in the presence of 1 mM alpha-ketomethiobutyrate and 30 mM total amino acid as substrates) and the individual, isolated enzymes. At 1 mg ml-1, canaline was found to inhibit cell growth in vitro by 62%, and carboxymethoxylamine caused cell death within 24 h.
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PMID:Methionine formation from alpha-ketomethiobutyrate in the trypanosomatid Crithidia fasciculata. 974 3

An important increase of plasma hormone levels like insulin, TSH and aldosterone was observed in human subjects after space flights, however in the changes of plasma content of ACTH, cortisol, adrenaline and noradrenaline the individual variations were observed in relation to number and duration of space flight. For evaluation of the effects of these changes in plasma hormone levels on metabolic processes also the experiments with small animals subjected to space flights on a board of biosatellite of Cosmos series were running. An elevation of plasma levels of corticosterone, adrenaline, noradrenaline and insulin was found in rats after the space flights of duration from 7 to 20 days. It was demonstrated, that the increase of corticosterone in plasma is followed by the activation of enzymes involved in the amino acid metabolism in rat liver (tyrosine aminotransferase, tryptophanpyrolase, alanine aminotransferase and aspartate aminotransferase). After a short recovery period (2 to 6 days) the plasma corticosterone concentration and also the activity of liver enzymes returned to control levels. The exposition of animals to stress stimuli during this revcovery period showed higher response of corticosterone levels in flight rats as compared to intact controls. The increase of plasma catecholamine levels was not followed by elevation of lipolysis in adipose tissue. This is due to lower response of adipose tissue to catecholamine because a decrease of the stimulation of lipolysis by noradrenaline was observed in animals after space flight. The increase of insulin was not followed by adequate decrease of glucose concentration suggesting a disturbances in glucose utilization similarly as in cosmonauts after a long-term space flight. These results showed that changes in plasma hormone levels, observed after space flight, affected the regulation of metabolic processes in tissues.
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PMID:Effect of space flights on plasma hormone levels in man and in experimental animal. 1153 12

The aim of present experiment was to study the changes of corticosterone, insulin and glucose levels in plasma, of the activity of enzymes involved in aminoacid metabolism in liver and the binding of insulin to specific receptors of cell membrane from liver and also of adipose tissue of rats exposed to space flight for 14 days on biosatellite Cosmos 2044. Adult male Wistar rats (body mass 300-370 g) were divided into five groups: intact control rats (AC), rats exposed to space flight (F), animals in synchronous model experiment (S), rats in antiorthostatic hypokinesia (A) and so called operated control group (C). Half of all groups (5 animals) except the intact control were operated 3 days before the experiment (fibulas on both hind legs were broken). The flight animals were sacrificed 5-6 hours after landing. It was observed that plasma insulin levels are increased in rat exposed to 14-day space flight and in synchron experiments. A significant increase of plasma glucose levels was found in flight rats in spite of high insulin concentrations suggesting that in rats exposed to 14-day space a deterioration of tissue sensitivity to insulin could by present. No significant differences of specific insulin binding to liver plasma membrane fraction in flight and intact control animals were observed. A decrease of insulin binding capacity in liver was found in rats in antiorthostatic hypokinesia (A). However in the membrane of adipocytes an important increase of insulin receptors was noted in rats subjected to space flight. These results suggest, that the liver and adipocyte insulin receptors of flight rats did not respond to the increased plasma insulin levels by "down regulation". The determination of plasma corticosterone levels showed that in flight rats and animals exposed to antiorthostatic hypokinesia the plasma hormone levels are significantly elevated. A significant increase of tyrosine aminotransferase and tryptophan pyrrolase activities in liver of flight rats and those exposed to hypokinesia was observed. Also the elevation of alanine amino-transferase in liver was observed in flight rats, while, the activity of aspartate aminotransferase in liver was similar in control and flight animals. These results showed that the changes in liver enzyme activities in rats after 14-day space flight are in agreement with the results observed in previous experiments after a shorter space flight (7 days).
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PMID:The effect of space flight on the board of the satellite Cosmos 2044 on plasma hormone levels and liver enzyme activities of rats. 1154 60

The activity of the enzymes involved in aminoacid metabolism (tyrosine aminotransferase, TAT, tryptophan pyrrolase TP, serine dehydratase, SD) with rapid response to glucocorticoids and enzymes requiring for activity increase repeated administration of corticosterone (alanine aminotransferase, ALT, aspartate aminotransferase, AST) in liver, the changes of lipolysis in adipose tissue and the plasma corticosterone levels were studied in rats subjected to space flight (F), in animals from synchron model experiments (SM, simulated conditions of space flight in laboratory) and in intact controls (C). The increase of plasma corticosterone concentration and of the activity of rapidly (TAT, TP, SD) and slowly activating enzymes (ALT, AST) was found in F group 6-10 hr after space flight (18.5 days on biosatellite COSMOS 1129). This suggested the presence of acute-stress (associated primarily with the landing) and chronic stress induced hypercorticosteronemia during the flight. After the short 6-day period of recovery the plasma corticosterone concentrations and the activities of liver enzymes returned to control levels. The exposition of animals to repeated immobilization stress showed higher response of corticosterone levels in flight rats as compared to intact controls. No changes in basal lipolysis were observed in flight rats in comparison to intact controls, however the stimulation of lipolysis by norepinephrine was lower in animals from F and SM groups. This lower response of lipolytic processes to norepinephrine was found in flight animals also after six days period of recovery. These results showed that there are important changes in the regulation of lipolytic processes in adipose tissue of rats after space flight and in the conditions of model experiments.
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PMID:Metabolic changes in the animals subjected to space flight. 1154 92

1. Two experiments were conducted to investigate the impact of high temperature and dietary tyrosine (Tyr) content on performance and activity of hepatic tyrosine aminotransferase (EC 2.6.1.5.), an enzyme that catalyses the first step in the metabolic degradation of Tyr in broiler chickens. 2. Two-week-old birds were allocated to one of three temperature treatments: 24 degrees C (control), 36 degrees C (heat stress, HS) and 24 degrees C pair-fed (24PF) for 2 weeks and fed on diets containing 100% (Experiment 1) and 50, 100 and 200% (Experiment 2) of the NRC requirement for Tyr. 3. In Experiment 1, exposure of chickens to 36 degrees C for 2 weeks caused significant increase in hepatic tyrosine aminotransferase activity but no significant change in activity of hepatic phenylalanine 4-hydroxylase (EC 1.14.16.1) (an enzyme that catalyses conversion of phenylalanine to Tyr) compared with the 24PF birds. No significant changes attributable to heat stress were detected in hepatic glutamic-oxaloacetic transaminase (EC 2.6.1.1) activity. 4. In Experiment 2, heat stress caused reductions in weight gain and feed intake in chickens on all diets, compared with their control counterparts. Hepatic tyrosine aminotransferase activity was increased by heat stress compared with their 24PF counterparts in chickens fed on the 100 and 200% Tyr diets, while in chickens fed the 50% Tyr diet, it was reduced by heat stress. 5. From these results, it is suggested that hepatic tyrosine aminotransferase activity is affected by heat stress and dietary Tyr content and the increased tyrosine aminotransferase activity with, in part, relatively low phenylalanine hydroxylase activity in hepatic tissues may be involved in the Tyr metabolism characteristic of heat-stressed chickens.
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PMID:Hepatic tyrosine aminotransferase activity is affected by chronic heat stress and dietary tyrosine in broiler chickens. 1236 21

The six mutations, referred to as the Hex mutations, that together have been shown to convert Escherichia coli aspartate aminotransferase (AATase) specificity to be substantially like that of E. coli tyrosine aminotransferase (TATase) are dissected into two groups, (T109S/N297S) and (V39L/K41Y/T47I/N69L). The letters on the left and right of the numbers designate AATase and TATase residues, respectively. The T109S/N297S pair has been investigated previously. The latter group, the "Grease" set, is now placed in the AATase framework, and the retroGrease set (L39V/Y41K/I47T/L69N) is substituted into TATase. The Grease mutations in the AATase framework were found primarily to lower K(M)s for both aromatic and dicarboxylic substrates. In contrast, retroGrease TATase exhibits lowered k(cat)s for both substrates. The six retroHex mutations, combining retroGrease and S109T/S297N, were found to invert the substrate specificity of TATase, creating an enzyme with a nearly ninefold preference (k(cat)/K(M)) for aspartate over phenylalanine. The retroHex mutations perturb the electrostatic environment of the pyridoxal phosphate cofactor, as evidenced by a spectrophotometric titration of the internal aldimine, which uniquely shows two pK(a)s, 6.1 and 9.1. RetroHex was also found to have impaired dimer stability, with a K(D) for dimer dissociation of 350 nM compared with the wild type K(D) of 4 nM. Context dependence and additivity analyses demonstrate the importance of interactions of the Grease residues with the surrounding protein framework in both the AATase and TATase contexts, and with residues 109 and 297 in particular. Context dependence and cooperativity are particularly evident in the effects of mutations on k(cat)/K(M)(Asp). Effects on k(cat)/K(M)(Phe) are more nearly additive and context independent.
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PMID:Quantitative chimeric analysis of six specificity determinants that differentiate Escherichia coli aspartate from tyrosine aminotransferase. 1244 83

Aspartate aminotransferase (AATase) and tyrosine aminotransferase (TATase) are Escherichia coli paralogs that share 43% sequence identity. A plausible model posits that TATase arose from a duplication of an ancestral AATase-like enzyme. Directed evolution of AATase to an enzyme having TATase activity was undertaken in order to compare the evolved AATase variants with homologous TATases. Eight rounds of DNA shuffling and in vivo selection followed by a backcross with WT AATase produced enzymes that exhibited 100-270-fold increases in k(cat)/K(m)(Phe) and had as much as 11% of the tyrosine aminotransferase activity of WT E.coli TATase. Amino acid substitutions in 11 clones from rounds 7 and 8 were compared with conserved residues in AATases and TATases. The findings are conveniently and compactly illustrated by the use of Venn diagrams and set theory notation. A statistically significant (0.001<or=p<or=0.008) concentration of mutations occurs in a subset of positions (set AAT-TAT) that is conserved (>or=75% identical) in AATases and variable (<75% identical) in TATases. Very few mutations occur in the intersection (set AAT intersection TAT) of amino acid residues that are conserved in both enzyme types. Seven mutations from set AAT-TAT were combined by site-directed mutagenesis to give a construct that is 60% as active as the best round 8 enzyme, which has 13 amino acid replacements. The Venn diagrams may provide a generally useful tool to highlight the most important specificity determinants for rational redesign. Amino acid replacements were mapped onto the crystal structure of a hydrocinnamate complex of a designed TATase. Five of the seven positions most frequently substituted in the evolved clones are within 15 A of the phenyl side-chain, but only six of the 48 positions that were mutated once or twice are within that radius. Context dependence, neutral mutations, different selective pressures, and stochastic components provide explanations for the observation that many of the substitutions found in the directly evolved enzymes differ from the corresponding amino acids found in the modern natural TATases.
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PMID:How does an enzyme evolved in vitro compare to naturally occurring homologs possessing the targeted function? Tyrosine aminotransferase from aspartate aminotransferase. 1263 55

The homodimeric, pyridoxal 5'-phosphate (PLP)-dependent enzyme glutamine transaminase K/cysteine conjugate beta-lyase (GTK/beta-lyase) has been implicated in the bioactivation of chemopreventive compounds. This paper describes the first homology model of rat renal GTK/beta-lyase and its active site residues, deduced from molecular dynamics (MD) simulations of the binding mode of 13 structurally diverse cysteine S-conjugates and amino acids after Amber-parametrization of PLP. Comparison with Thermus thermophilus aspartate aminotransferase (tAAT) and Trypanosoma cruzi tyrosine aminotransferase (tTAT), used as templates for modeling GTK/beta-lyase, showed that the PLP-binding site of GTK/beta-lyase is highly conserved. Binding of the ligand alpha-carboxylate-group occurred via the conserved residues Arg(432) and Asn(219), and Asn(50) and Gly(70). Two pockets accommodated the various ligand side chains. A small pocket, located directly above PLP, was of a highly hydrophobic and aromatic character. A larger pocket, formed partly by the substrate access channel, was more hydrophilic and notably involved the salt bridge partners Glu(54) and Arg(99*) (* denotes the other subunit). Ligand-binding residues included Leu(51), Phe(71), Tyr(135), Phe(373) and Phe(312*), and pi-stacking interactions were often observed. Tyr(135) and Asn(50) were prominent in hydrogen bonding with the sulfur-atom of cysteine S-conjugates. The observed binding mode of the ligands corresponded well with their experimentally determined inhibitory potency toward GTK/beta-lyase. The current homology model thus provides a starting point for further validation of the role of active site residues in ligand-binding by means of mutagenesis studies. Ultimately, insight in the binding of ligands to GTK/beta-lyase may result in the rational design of new ligands and selective inhibitors.
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PMID:Modeling and molecular dynamics of glutamine transaminase K/cysteine conjugate beta-lyase. 1279 91


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