Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After borohydride reduction, carboxymethylation, and tryptic digestion of the holoenzyme of pig heart alanine aminotransferase, a single icosapeptide containing the N6-(phosphopyridoxyl)lysine residue was isolated by a combination of gel filtration and ion-exchange chromatogrpahy. Its primary structure was determined as Gln-Glu-Leu-Ala-Ser-Phe-His-Ser-Val-Ser-Lsy(Pxy)-Gly-Phe-Met-Gly-Glu-Cys-Gly-Phe-Arg.
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PMID:Pyridoxal 5'-phosphate binding site of pig heart alanine aminotransferase. 46 50

Using a single-isotope and immune precipitation technique the half-life (t 1/2) of hepatic phenylalanine:pyruvate transaminase (aminotransferase, EC 2.6.1.--, Number not yet assigned) from glucagon-treated rats was determined to be 2.8 days, similar to that of the control rats (t 1/2 = 3.3 days). The half-life of rat liver total soluble proteins also remained unchanged after glucagon treatment (t 1/2 = 2.7 days in glucagon-treated rats; t 1/2 = 2.8 days in normal). Thus, glucagon has no effect on the degradation of phenylalanine:pyruvate transaminase. Furthermore, the degradation rates are similar for both the holoenzyme and the apoenzyme of phenylalanine:pyruvate transaminase.
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PMID:Degradation of phenylalanine:pyruvate transaminase after glucagon treatment. 68 44

Changes in serum amino acid levels and time course of hepatic function derangements were studied in mongrel dogs with choledochus ligature and subsequent biliarly reconstruction through cholecysto-duodenostomy. In the second week after choledochus ligature, serum ammonium level increased along with intensification of jaundice. After four weeks, GPT activity was higher than GOT and plasma albumin level markedly decreased with similar reduction in serum amino acid levels. Biliary reconstruction, when performed during three or four weeks after the ligature, restored the hepatic function as well as serum amino acid levels toward normal. When it was performed in the fifth or sixth week after the ligation, the liver function did not restore and serum levels of total amino acids, essential and non-essential amino acids increased even 4 weeks lapse after reconstruction. Among the changes observed, His., Val., Ser., Arg., Leu., Ileu, Phe, and Lys. were increased, whereas Pro. and Cys. disappeared from the serum. These results suggest that recovery from metabolic changes of amino acids due to choledochus ligature depends upon the duration of obstructive jaundice, i.e., it appears necessary to perform the biliary reconstruction within four weeks after the initiation of obstruction.
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PMID:[Experimental study on changes in serum amino acid levels following choledochus ligature and subsequent biliary reconstruction (author's transl)]. 82 88

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 synthesis and release of alanine and glutamine have been studied in the intact rat epitrochlaris skeletal muscle preparation. Aspartate, cysteine, leucine, valine, methionine, isoleucine, serine, theronine, and glycine increased significantly the formation and release of alanine from muscle. Cysteine, leucine, valine, methionine, isoleucine, tyrosine, lysine, and phenylalanine increased the rate of glutamine synthesis. Only ornithine, arginine, and tryptophan were without effect on the synthesis of either alanine or glutamine. Half-maximal stimulation of alanine and glutamine formation by added amino acids was observed with concentrations ranging between 0.5 and 1.0 mM. Increases in alanine and glutamine formation were not accompanied by changes in pyruvate production or glucose uptake. The progressive decline in alanine and glutamine synthesis noted on prolonged incubation was prevented by the addition of amino acids to the incubation medium. Stimulation of alanine synthesis by added amino acids was unaffected by inhibition of glycolysis with iodoacetate. Inhibition of alanine aminotransferase with aminooxyacetate significantly decreased alanine formation. Pyruvate and ammonium chloride did not increase further the rate of either alanine or glutamine formation above that produced by added amino acids. These data indicate that most amino acids are precursors for alanine and glutamine synthesis in skeletal muscle. A general mechanism is presented for the de novo formation of alanine from amino acids in skeletal muscle, and the importance of proteolysis for the supply of amino acid precursors for alanine and glutamine synthesis is discussed.
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PMID:Alanine and glutamine synthesis and release from skeletal muscle. II. The precursor role of amino acids in alanine and glutamine synthesis. 124 59

To explore the relationship between intestinal fluid absorption and oxidative metabolism, we measured the effects of amino acids and glucose on piglet jejunal ion transport and oxygen consumption (QO2) in vitro. Jejunal QO2 was stimulated by L-glutamine and D-glucose but not by the nonmetabolizable organic solutes methyl beta-D-glucoside or L-phenylalanine. QO2 was maximally enhanced by the combination of D-glucose and L-glutamine (5 mM). Even though 5 mM L-glutamine was previously found to be insufficient to stimulate NaCl absorption, 5 mM L-glutamine enhanced jejunal NaCl flux when combined with equimolar mucosal D-glucose. Either D-glucose or methyl beta-D-glucoside caused an increase in short-circuit current (Isc), an increase in Na+ absorption in excess of Isc, and a decrease in Cl- secretion, when L-glutamine was substituted for D-glucose (10 mM) on the serosal side. This relationship suggests that mucosal sugars, if combined with L-glutamine, enhance neutral NaCl absorption as well as electrogenic Na+ flow. (Aminooxy)acetate, an inhibitor of alanine aminotransferase, abolished the stimulation of QO2 and the NaCl-absorptive response to L-glutamine. We conclude that the oxidative metabolism fueled by L-glutamine is linked to a NaCl-absorptive mechanism in the intestine. We propose that the CO2 produced by glutamine metabolism yields carbonic acid, which dissociates to H+ and HCO3-, which may stimulate parallel antiports in the apical membrane.
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PMID:L-glutamine with D-glucose stimulates oxidative metabolism and NaCl absorption in piglet jejunum. 147 2

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

N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymers containing doxorubicin (DOX) and galactosamine can be targeted to the hepatocyte galactose receptor for organ-specific chemotherapy of primary and metastatic liver cancer. Here we report the dose-dependent pharmacokinetics of this macromolecular conjugate. Following intravenous administration to mice most efficient liver targeting was seen at low dose (0.05 mg DOX kg-1), with receptor saturation observed using higher bolus doses. Repeated low dose bolus injections did not cause down-regulation of the galactose receptor and targeted drug delivery rates of greater than or equal to 2 micrograms DOX g-1 liver h-1 were achieved. DOX is released from such conjugates intracellularly via action of lysosomal proteinases. It was shown that isolated rat liver lysosomal enzymes (Tritosomes) can release unmodified DOX from the peptidyl side chain Gly-Phe-Leu-Gly at a rate greater than or equal to 3 micrograms DOX g-1 liver h-1 i.e. the hydrolytic capacity is greater than the observed rate of drug delivery to the liver lysosomes in vivo. Although most conjugate would be captured by normal hepatocytes following intravenous administration, it was shown that the human hepatoma cell line HepG2 retains the galactose receptor, accumulating and processing the conjugate efficiently. Potential dose limiting toxicities of such drug conjugates could include cardio- or hepatotoxicity. Administration of conjugate reduced the 15 min heart level of DOX approximately 100-fold compared with that observed for an equivalent dose of free drug. Preliminary experiments showed that plasma levels of alkaline phosphatase, alanine transaminase and asparate transaminase did not change following administration of HPMA copolymer-daunorubicin (DNR) (10 mg DNR kg-1) indicating no significant heptatoxicity.
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PMID:N-(2-hydroxypropyl)methacrylamide copolymers targeted to the hepatocyte galactose-receptor: pharmacokinetics in DBA2 mice. 164 46

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

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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