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)

The activity of the aspartate-, alanine-, tyrosine-, phenylalanine- and tryptophane aminotransferases in the rat organes in development have been investigated by quantitative histochemical methods. The isoenzymes have also been examined. The variable increase of the aminotransferase activity has been observed in the liver, brain, heart, skeletal muscle and kidney. In spite of the differences of the aspartate aminotransferase activity in the organs, the increase up to the 7th postnatal day, the reduction after that and the repeated increase after the 14th day reaching the level of the adult animals is evident as a common trend. A considerable increase of the alanine aminotransferase activity has been observed in the late postnatal period. While the difference in the activity of the aromatic aminotransferases in the embryonic organs is small, the changes of the 3 enzymes are different in the postnatal development. The number and the intensity of the isoenzymes of the aspartate- and alanine aminotransferases increase in the development. The isoenzyme spectrum of aromatic aminotransferases in the embryo proves an equal in number and intensity of fractions. In the development this similarity is preserved only with regard to cathode isoenzymes, while with anode once some differences appear.
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PMID:Histochemical evidence of aminotransferases. 82 67

The sequences of the coenzyme-binding peptide of both cytoplasmic and mitochondrial aspartate aminotransferases from sheep liver were determined. The holoenzymes were treated with NaBH4 and digested with chymotrypsin; peptides containing bound pyridoxal phosphate were then isolated. One phosphopyridoxyl peptide was obtained from sheep liver cytoplasmic aspartate aminotransferase. Its sequence was Ser-Ne-(phosphopyridoxyl)-Lys-Asn-Phe. This sequence is identical with that reported for the homologous peptide from pig heart cytoplasmic aspartate aminotransferase. Two phosphopyridoxyl peptides with different RF values were isolated from the sheep liver mitochondrial isoenzyme. They had the same N-terminal amino acid and similar amino acid composition. The mitochondrial phosphopyridoxyl peptide of highest yield and purity had the sequence Ala-Ne-(phosphopyridoxyl)-Lys-Asx-Met-Gly-Leu-Tyr. The sequence of the first four amino acids is identical with that already reported for the phosphopyridoxyl tetrapeptide from the pig heart mitochondrial isoenzyme. The heptapeptide found for the sheep liver mitochondrial isoenzyme closely resembles the corresponding sequence taken from the primary structure of the pig heart cytoplasmic aspartate aminotransferase.
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PMID:The sequences of the coenzyme-binding peptide in the cytoplasmic and the mitochondrial aspartate aminotransferases from sheep liver. 118 Aug 94

We determined the molar ratio of branched-chain amino acids to tyrosine (BTR) in plasma and in serum by enzymatic method and compared it with Fischer ratio (the molar ratio of branched-chain amino acids to tyrosine and phenylalanine) in plasma obtained by conventional HPLC method. BTR in plasma and in serum was well correlated with plasma Fischer ratio. The normal range (mean +/- 2SD) of BTR was determined to be 4.41-10.05 in 210 normal subjects. In addition, we investigated the distribution of BTR values in patients with various liver diseases. BTR value decreased according to the severity of liver disease. We evaluated the clinical usefulness of BTR in patients with chronic liver diseases by cumulative distribution analysis (CDA) graph and receiver operating characteristic curve (ROC) analysis. The area under the curve for BTR analyzed by ROC for CH versus LC.HCC group was the highest (86.3%) of any for various concurrently-measured liver function tests, and was significantly higher than AST/ALT, ALT, AST, gamma-GT (each, p less than 0.001) and ALB (p less than 0.05). These diagnostic results showed that BTR is a superior indicator in discriminating between liver cirrhosis and chronic hepatitis.
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PMID:[The clinical usefulness of the molar ratio of branched-chain amino acids to tyrosine (BTR) in discriminating stage of chronic liver diseases]. 151 41

The distribution of amino acids between plasma, liver and brain was studied in adult male rats, fed a diet containing 8.7, 17 (control animals), 32 and 51% of protein during 15 days. The caloric intake was nearly equal in all groups. The highest food intake was observed in the animals on the low protein diet. Changes in plasma amino acids were variable. In contrast to the behavior of most amino acids in plasma, the branched chain amino acids were highest in the animals fed the 51% protein diet. Despite the low protein intake in the animals fed a 8.7% protein diet, the concentration of serine, glutamic acid, glutamine, glycine, alanine, methionine, isoleucine, leucine, phenylalanine and ornithine were significantly higher compared to control animals, whereas in those receiving a high protein diet, valine, leucine, tyrosine, tryptophan and histidine increased in relation to the increased protein and amino acid intake. The plasma amino acid patterns are not greatly influenced by the amino acid distribution in the food and the amount ingested. Alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase and cholinesterase showed a two- to fivefold increased activity in the liver of animals consuming a high protein diet. In the brain, the concentration of valine, leucine, isoleucine, phenylalanine and tyrosine in animals receiving the low protein diet was higher than in controls and increased further with increasing protein content of the diet. Glutamine was increased in all dietary groups. The predicted influx of amino acids showed increasing influx rates in dependence of the plasma amino acid concentration. The entry of tyrosine and tryptophan and their brain concentration was inversely proportional to the protein content of the diet. In the present study which considers long-term adaptation to an increasing protein and amino acid intake in comparison to a balanced control protein diet, the levels of the indispensable amino acids were maintained within narrow limits in the brain and liver. The results indicate that inspite of a variable protein intake, the body tends to keep organ amino acids in relatively narrow limits favoring in this way amino acid homeostasis.
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PMID:Effect of different protein diets on the distribution of amino acids in plasma, liver and brain in the rat. 159 Jun 69

Human liver cholesterol 7 alpha-hydroxylase (CYP7) cDNAs were isolated from a human liver cDNA library. A full-length cDNA has 2901 nucleotides which encode a typical P450 polypeptide of 504 amino acid residues. Two different sequences of codon 100, TTT (Phe) and TCT (Ser), were identified in cDNA clones. In addition, codons 347 and 385 are GAT (Asp) and GAC (Asp) in all cDNA clones, whereas those reported previously (FEBS Lett. 268, 137-140, 1990) are AAT (Asn) and AGC (Ser), respectively. Since there is only one 7 alpha-hydroxylase gene in the human genome, it is likely that polymorphisms at the codon 100 of cDNA clones arise from two different alleles in the 7 alpha-hydroxylase gene of this human liver.
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PMID:Polymorphisms of human cholesterol 7 alpha-hydroxylase. 161 Mar 52

Aspartate aminotransferase (mitochondrial isoenzyme from chicken) has been found to racemize very slowly dicarboxylic amino acid substrates in the presence of their cognate oxo acids [Kochhar, S. & Christen, P. (1988) Eur. J. Biochem. 175, 433-438]. Tyrosine, phenylalanine and alanine are racemized at the same rate although they undergo the transamination reaction 3-5 orders of magnitude more slowly than the dicarboxylic substrates. Similarly, the truncated enzyme aspartate aminotransferase-(27/32-410) catalyzes the racemization at the same rate as the native enzyme, while its rate of transamination is decreased to 3% of that of the native enzyme. Apparently, the rate-limiting step in racemization is not immediately linked to the transamination cycle. Decreasing the water concentration in the reaction medium by adding methanol at 0 degrees C drastically reduces the rate of racemization without affecting the rate of transamination. On the basis of these and additional kinetic data and the model of the three-dimensional structure of the active site, we conclude that a water molecule is responsible for the protonation of C alpha of the coenzyme-substrate intermediate from the wrong side. The diffusion of the water molecule into the interior of the enzyme appears to be the rate-limiting step in aspartate-aminotransferase-catalyzed racemization.
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PMID:Mechanism of racemization of amino acids by aspartate aminotransferase. 173 41

In a clinical setting, the effect of Eurocollins (EC) and University of Wisconsin solution (UW) on liver grafts were studied in the early reperfusion phase of liver transplantation. Blood samples were drawn before and after declamping of the portal vein in a group of 11 transplants with EC-perfused livers, and a group of 12 transplants with UW-perfused livers. Parenchymal damage was assessed by the LDH, AST, and ALT, and purine degradation by measuring the uric acid levels. Metabolic function was determined by the serum bile acids and the plasma amino acids, i.e. (valine + leucine + isoleucine)/(phenylalanine + tyrosine) ratio. Donor and pretransplant recipient parameters were almost identical. The cold ischemia time of both groups differed significantly. The results show the following: a significant difference between both the LDH and the uric acid levels in the two groups was revealed, with a smaller increase of the LDH levels and no increase of the uric acid levels in the UW group. Metabolic activity, as measured from the bile acids and the amino acid profile in the peripheral blood, was identical in both groups. We conclude that both EC-stored and UW-stored liver grafts show immediate metabolic function after reperfusion. The amount of metabolic function was equal in both groups, notwithstanding longer cold ischemia time in the UW group. In addition, more parenchymal damage occurred in the EC group.
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PMID:Cellular damage and early metabolic function of transplanted livers stored in Eurocollins or University of Wisconsin solution. 180 31

Site-directed mutagenesis of Tyr70 in the active site of Escherichia coli aspartate aminotransferase (AspAT) followed by kinetic studies has elucidated the roles of the hydroxyl group and benzene ring of Tyr70. X-ray crystallographic analysis showed that replacement of Tyr70 by Phe did not alter the active-site conformation of the enzyme. Comparison of the kinetic parameters of the four half-transamination reactions (the pyridoxal 5'-phosphate form of the enzyme with L-aspartate or L-glutamate and the pyridoxamine 5'-phosphate form with oxalacetate or 2-oxoglutarate) between the wild-type and [Tyr70----Phe]AspATs showed that the mutation increases the energy level of the transition state by 2 kcal.mol-1 for all the four substrates, suggesting some contribution of the hydroxyl group of Tyr70 to the transition state. When Phe70 was further replaced by Ser, the energy level of the transition state for L-glutamate or 2-oxoglutarate, but not for L-aspartate or oxalacetate, was further increased by 2-3 kcal.mol-1, suggesting that the presence of a benzene ring at position 70 is essential for recognizing the L-glutamate-2-oxoglutarate pair as substrates.
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PMID:Site-directed mutagenesis of Escherichia coli aspartate aminotransferase: role of Tyr70 in the catalytic processes. 186 57

Tyr225 in the active site of Escherichia coli aspartate aminotransferase (AspAT) was replaced by phenylalanine or arginine by site-directed mutagenesis. X-ray crystallographic analysis of Y225F AspAT showed that the benzene ring of Phe225 was situated at the same position as the phenol ring of Tyr225 in wild-type AspAT. The mutations resulted in a great decrease in the rate of the transamination reaction, suggesting that Tyr225 is important for efficient catalysis. The kinetic analysis of half-transamination reactions of Y225F AspAT with four substrates (aspartate, glutamate, oxalacetate, and 2-oxoglutarate) and some analogues (2-methylaspartate, succinate, and glutarate) revealed a considerable increase in the affinities for all these compounds. In contrast, affinity for the amino acid substrates was decreased by mutation to arginine, but affinities for the keto acid substrates and the two dicarboxylates (succinate and glutarate) were increased. The electrostatic interaction between O(3') of the coenzyme [pyridoxal 5'-phosphate (PLP)] and the residue at position 225 affected the pKa value of the Schiff base, which is formed between the epsilon-amino group of Lys258 and the aldehyde group of PLP; based on the spectrophotometric titration the pKa values were determined to be 6.8 for wild-type AspAT, 8.5 for Y225F AspAT, and 6.1 for Y225R AspAT in the absence of substrate. The absorption spectra of the three AspATs were almost identical in the acidic pH region, but the spectrum of Y225F AspAT differed from that of wild-type or Y225R AspAT in the alkaline pH region.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tyr225 in aspartate aminotransferase: contribution of the hydrogen bond between Tyr225 and coenzyme to the catalytic reaction. 186 10

Ten minutes after an intravenous flooding dose of phenylalanine to rats, plasma sodium and calcium concentrations were slightly reduced (by 2-7%) but no effects on potassium or phosphate were observed. Creatine kinase activities were significantly increased by phenylalanine injection (by 39%), but alkaline phosphatase, alanine aminotransferase, lactate dehydrogenase and aspartate aminotransferase activities were unaltered. Plasma concentrations of total proteins, albumin, cholesterol, triglycerides, urea, creatinine and glucose were also unaffected. In the presence of anaesthesia, phenylalanine injection had almost identical effects, although the increase in creatine kinase activities did not reach statistical significance. Anaesthesia for 10 min reduced plasma potassium concentrations (by 27%), and calcium (by 5%), though phosphate and sodium were unaltered. The activities of lactate dehydrogenase, creatine kinase and aspartate aminotransferase were reduced by between 36-52%, but alkaline phosphatase and alanine aminotransferase activities were unaltered by anaesthesia. Plasma concentrations of total proteins and albumin were also reduced (both by 9%), but glucose concentrations were increased (by 33%). Anaesthesia had no other significant effects on cholesterol, triglycerides, urea or creatinine concentrations. The qualitative effects of anaesthesia in the presence of raised free phenylalanine concentrations were similar. It was concluded that, except for creatine kinase, determinations of plasma constituents in phenylalanine-injected rats could be made without overt interpretational errors. However, caution is required in interpreting data on plasma constituents from anaesthetized rats.
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PMID:Measurement of protein synthesis by the phenylalanine flooding dose technique: effect of phenylalanine and anaesthesia on plasma electrolyte, enzyme and metabolite levels. 198 47


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