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)

1. Methods are described for monitoring the metabolic flux through phenylalanine hydroxylase, the tyrosine catabolic pathway and phenylalanine: pyruvate transaminase in isolated liver cell incubations. 2. The relationship between hydroxylase flux and phenylalanine concentration is sigmoidal. 3. Glucagon increases hydroxylase activity at low, near-physiological, substrate concentrations only. The hormone does not affect the rate of formation of phenylpyruvate. 4. Experimental diabetes (for 10 days) increases phenylalanine catabolism, and this is further increased by glucagon. 5. These results are discussed in the light of the known mechanisms for control of phenylalanine hydroxylase activity in vitro.
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PMID:Phenylalanine metabolism in isolated rat liver cells. Effects of glucagon and diabetes. 732 31

We studied the effect of L-glutamine (Gln), the principal intestinal fuel, on proliferation of a porcine jejunal cell line, IPEC-J2. In cells synchronized by serum deprivation for 4 h, Gln stimulated ornithine decarboxylase (ODC; EC 4.1.1.17) in a dose- and time-dependent manner, with maximal effects at 10 mM in 3 h (P < 0.01). Similar effects were seen for the structurally related amino acid L-asparagine and serum. The Gln effect on ODC was specific, as isosmolar mannitol, glucose, methyl-beta-D-glucoside, L-phenylalanine, ammonia, and aminoisobutyric acid were ineffective. The alanine aminotransferase inhibitor aminooxyacetate (AO) inhibited the ODC stimulation by Gln in a dose-dependent manner (half-maximal inhibitory concentration = 0.5 mM). AO was not toxic to cells, as determined by propidium iodide uptake into nuclei. In addition, Gln stimulated a twofold increase of cellular 24-h [3H]thymidine incorporation above rates of control cells bathed in standard media (P < 0.01); this effect was also blocked by AO. Gln and phorbol 12-myristate 13-acetate stimulated ODC in a synergistic manner. The Na+/H+ exchange inhibitor methylisobutyl amiloride blocked the enhancement of ODC by Gln. Gln also induced the mRNA of the immediate-early gene c-jun. Gln stimulates proliferation in a porcine jejunal cell line through a mechanism requiring transamination and intact Na+/H+ exchange. This stimulation of enterocyte proliferation by Gln suggests that therapeutic Gln administration could facilitate epithelial recovery in the injured small intestine.
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PMID:L-glutamine and L-asparagine stimulate ODC activity and proliferation in a porcine jejunal enterocyte line. 748 12

Serum amino acid (AA) profiles are altered in epilepsy. It is not clear whether this is due to the disease process itself or to other variables such as seizure type, seizure frequency, duration of illness, medication, or altered liver function. We investigated serum AA profiles and liver enzymes in 73 epileptic patients and 90 healthy subjects and evaluated the data by analysis of variance to discriminate between age, sex, seizure type, duration of illness, seizure frequency, antiepileptic drug (AED) and increased serum liver enzyme levels, and their putative interaction with the serum AA profile. There was no correlation between the changes in the AA profile and age, duration of illness, seizure frequency, and seizure type. Seventy-two percent of the AED-treated patients and 33% of the unmedicated patients showed an increase in one or several serum liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or gamma-glutamyl transferase (gamma-GT)]; particularly gamma-GT. We observed a significant increase in serum concentrations of glutamine and glycine and decreased levels of taurine, threonine, serine, valine, methionine, isoleucine, leucine, phenylalanine, histidine, tryptophan, and arginine in AED-treated patients but not in unmedicated patients. These results show that the changes in the serum AA profiles of epileptic patients treated with AEDs occur in patients with alteration of serum liver enzymes; whether this implies a causal relation is still uncertain.
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PMID:Serum amino acids, liver status, and antiepileptic drug therapy in epilepsy. 809 92

Tyrosine aminotransferase was purified to homogeneity from epimastigotes of Trypanosoma cruzi by a method involving chromatography on DEAE-cellulose, gel filtration on Sephacryl S-200 and chromatography on Mono Q in an f.p.l.c. system. The purified enzyme showed a single band in SDS/PAGE, with an apparent molecular mass of 45 kDa. Since the apparent molecular mass of the native enzyme, determined by gel filtration, is 91 kDa, the native enzyme is a dimer of similar subunits. The amino-acid composition was determined, as well as the sequences of three internal peptides obtained by CNBr cleavage at Met residues. Both criteria suggest considerable similarity with the tyrosine aminotransferases from rat and from human liver. The enzyme contains nine 1/2 Cys residues, three free and the others forming three disulphide bridges. The enzyme is not N-glycosylated. The isoelectric point is 4.6-4.8. The optimal pH for the reaction of the enzyme with tyrosine as a substrate is 7.0. The apparent Km values for tyrosine, phenylalanine and tryptophan, with pyruvate as a co-substrate, were 6.8, 17.9 and 21.4 mM, respectively, whereas those for pyruvate, alpha-oxoglutarate and oxaloacetate, with tyrosine as a substrate, were 0.5, 38 and 16 mM respectively. The purified tyrosine aminotransferase acts as an alanine aminotransferase as well and the activity seems to reside in the same enzyme molecule. The results suggest that the enzyme is a general aromatic-amino-acid transaminase, with high sequence similarity to tyrosine aminotransferases from rat and human liver.
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PMID:Purification and partial structural and kinetic characterization of tyrosine aminotransferase from epimastigotes of Trypanosoma cruzi. 810 Apr 16

Activated polymorphonuclear neutrophils (PMNs) have been shown to be cytotoxic to rat hepatic parenchymal cells in vitro. This cytotoxicity could be observed without direct cell-cell contact, since the conditioned medium from PMNs activated with formyl-Met-Leu-Phe (fMLP) was effective in hepatocyte killing. To identify the toxic factor(s) released by PMNs, degranulation was induced by fMLP in PMNs pretreated with cytochalasin B. The contents released from the phagocytes were subjected to gel filtration on a Sephadex G-100 column. Resulting fractions were tested for cytotoxicity to isolated hepatocytes by using release of alanine aminotransferase as a marker for hepatocyte injury. Cytotoxicity was associated with fractions containing cathepsin G and elastase and not with other fractions, including those containing myeloperoxidase. The former two enzymes were purified to homogeneity with a carboxymethyl cellulose column. Each of these enzymes demonstrated concentration-dependent cytotoxicity to hepatocytes at concentrations > 2 microgram/mL. Moreover, they exhibited an additive cytotoxic effect. Effective concentrations for the combined cathepsin G and elastase in the incubation mixture were similar to the concentrations of these enzymes in PMN-conditioned medium that produced cytotoxicity to hepatocytes. Cytotoxicity of either purified enzyme or of conditioned medium could be prevented by plasma alpha-1-antitrypsin or soybean trypsin-chymotrypsin inhibitor, which were also potent inhibitors of enzymic activity of both cathepsin G and elastase. By contrast, the serine protease inhibitors, aprotinin and 4-(2-aminoethyl)-benzene-sulfonyl fluoride, were less effective in inhibiting cathepsin G and elastase activities as well as cytotoxicity caused by the purified proteases or PMN-conditioned medium. These results support the hypothesis that cathepsin G and elastase are important mediators of hepatic parenchymal cell killing produced by activated PMNs in vitro.
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PMID:Identification of factors from rat neutrophils responsible for cytotoxicity to isolated hepatocytes. 865 57

Polymorphonuclear leukocytes (PMNS) have been implicated as cellular mediators of hepatic injury in models of inflammation in vivo. In vitro, hepatocyte killing by activated PMNs is mediated in part by proteases, but the role of nitric oxide is unknown. NO is produced by PMNs and hepatocytes and can act either to damage or protect in various models of toxicity. Therefore, we tested the hypothesis that NO is important in PMN-mediated hepatocyte killing in vitro. Freshly isolated hepatocytes from rat liver and PMNs elicited from rat peritoneum were cultured together or alone for 16 hours. Both cell types spontaneously released NO, estimated as its stable breakdown product, nitrite. Accumulation of nitrite in medium from hepatocyte cultures was augmented threefold by incubation with L-arginine and was completely inhibited by treatment with the nitric oxide synthase (NOS) inhibitor NG-methyl-L-arginine (NMA). Nitrite release in PMN cultures was unaffected by L-arginine addition and only partially inhibited by NMA. In PMN:hepatocyte cocultures (10:1), accumulation of nitrite was additive relative to cells cultured separately. Incubation with NMA blocked nitrite production completely in cocultures, whereas L-arginine caused a two-fold increase in nitrite. Addition of PMN stimulants, N-formyl-methionyl-leucyl-phenylalanine (FMLP), or phorbol myristate acetate (PMA), caused increased release of alanine aminotransferase (ALT) activity into medium from hepatocytes cultured with PMNs but not from hepatocytes cultured alone; this indicated that injury to hepatocytes was due to activated PMNS. However, neither FMLP nor PMA significantly altered nitrite release from cocultures. Despite the alterations in NO production induced by addition of NMA or L-arginine, neither agent altered the release of ALT from hepatocytes in coculture with activated PMNs. Thus, PMNs and hepatocytes provided NO in vitro, but neither suppression nor elevation of NO production affected PMN-mediated hepatocyte killing. Accordingly, NO is not involved in the mechanisms by which FMLP-or PMA-stimulated PMNs mediate hepatocyte injury in vitro.
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PMID:Nitric oxide is not involved in hepatocyte killing by neutrophils activated by N-formyl-methionyl-leucylphenylalanine or phorbol myristate acetate in vitro. 866 35

When activated, inflammatory cells such as polymorphonuclear leukocytes (PMNs) can damage isolated hepatocytes in vitro. These studies were performed to determine if flutamide activates PMNs. Flutamide (Eulexin) is an orally active, nonsteroidal antiandrogen that can cause liver injury associated with inflammation. Activation of PMNs was assessed from the production of superoxide anion and the release of myeloperoxidase in the presence or absence of flutamide and phorbol myristate acetate (PMA) or f-methionyl-leucyl-phenylalanine (fmlp). In addition, hepatocytes were cocultured with PMNs stimulated with PMA or fmlp in the presence or absence of flutamide, and cytotoxicity to hepatocytes was evaluated from the release of alanine aminotransferase into the medium. Flutamide alone did not stimulate the generation of superoxide anion by PMNs but potentiated its production in response to PMA. At lower concentrations of flutamide (i.e. 25 microM), there was a tendency toward increased release of myeloperoxidase, whereas at higher concentrations (i.e. 75-100 microM) flutamide inhibited degranulation in response to fmlp. In coculture with hepatocytes, PMNs exposed to either flutamide, fmlp, or PMA alone caused a significant increase in release of alanine aminotransferase. Hepatocellular toxicity caused by PMNs incubated with flutamide and PMA was additive and was not affected by the addition of superoxide dismutase and catalase. Flutamide had no significant effect on fmlp-induced injury in cocultures. These data indicate that flutamide alters the activation of PMNs by subsequent stimuli in vitro. In addition, in the presence of flutamide, minor PMN-mediated injury to isolated hepatocytes was observed.
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PMID:Alteration by flutamide of neutrophil response to stimulation. Implications for tissue injury. 917 23

We tested the hypothesis that nutritional state affects seawater acclimation by transferring either fed or food-deprived (2 weeks) male tilapia (Oreochromis mossambicus) from fresh water to full-strength sea water. Food-deprivation resulted in a significant increase in plasma concentrations of Na+, Cl-, cortisol, glucose, total amino acid, glutamate, serine and alanine, and in hepatic pyruvate kinase (PK) and lactate dehydrogenase (LDH) activities, whereas the prolactin-188 to prolactin-177 ratio (tPRL188:tPRL177) and plasma prolactin-188 (tPRL188), lactate, arginine and hepatic glycogen content and hepatic alanine aminotransferase (AlaAT) and 3-hydroxyacyl-Coenzyme A dehydrogenase (HOAD) activities were lower than in the fed group. Seawater transfer significantly increased the tPRL188:tPRL177 ratio and plasma concentrations of Na+, Cl-, K+, growth hormone (GH), glucose, aspartate, tyrosine, alanine, methionine, phenylalanine, leucine, isoleucine and valine levels as well as gill Na+/K+-ATPase activity and hepatic PK and LDH activities, whereas plasma tPRL177, tPRL188, glycine and lysine concentrations were significantly lower than in fish retained in fresh water. There was a significant interaction between nutritional state and salinity that affected the tPRL188:tPRL177 ratio and plasma concentrations of Cl-, GH, glucose, aspartate, tyrosine, serine, alanine, glycine, arginine and hepatic PK, LDH, AlaAT, aspartate aminotransferase, glutamate dehydrogenase and HOAD activities. These results, taken together, indicate that food-deprived fish did not regulate their plasma Cl- levels, despite an enhancement of plasma hormonal and metabolic responses in sea water. Our study also suggests the possibility that plasma prolactin and essential amino acids may be playing an important role in the seawater acclimation process in tilapia.
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PMID:Food-deprivation affects seawater acclimation in tilapia: hormonal and metabolic changes 932 Mar 94

In fulminant hepatic failure (FHF), the development of hepatic encephalopathy is associated with grossly abnormal concentrations of plasma amino acids (PAA). Normalization of the ratio of branched-chain amino acids to aromatic amino acids (Fischer's ratio) correlates with clinical improvement. This study evaluated changes in PAA metabolism during 4 h of isolated, normothermic extracorporeal liver perfusion using a newly designed system containing human blood and a rhesus monkey liver. Bile and urea production were within the physiological range. Release of the transaminases AST, ALT and LDH were minimal. The ratio of branched (valine, leucine, isoleucine) to aromatic (tyrosine, phenylalanine) amino acids increased significantly. These results indicate that a xenogeneic extracorporeal liver perfusion system is capable of significantly increasing Fischer's ratio and may play a role in treating and bridging patients in FHF in the future.
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PMID:Xenogeneic, extracorporeal liver perfusion in primates improves the ratio of branched-chain amino acids to aromatic amino acids (Fischer's ratio). 1035 51

Living organisms employ a variety of metabolic pathways when detoxifying xenobiotic compounds, including the formation of cysteine S-conjugates via glutathione conjugation. However, cysteine conjugate beta-lyase (CCBL) catalysed beta-cleavage, of certain cysteine conjugates, is known to cause cytotoxicity. This study represents the first investigation into the expression of CCBL and other associated enzymes in helminth species. A survey of the three major groups of parasitic helminths [cestodes (Moniezia expansa), digeneans (Fasciola hepatica) and nematodes (Necator americanus, Heligmosomoides polygyrus)] has been made. The presence of CCBL enzymes within Moniezia expansa, Necator americanus and Heligmosomoides polygyrus has been established. Each species was screened for gamma-glutamyl transpeptidase activity and transaminase activity towards L-aspartate, L-alanine, L-albizziin and L-phenylalanine. Aspartate and alanine aminotransferase activity were detected in all four species tested. Gamma-glutamyl transpeptidase activity was only detected in Moniezia expansa and Necator americanus.
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PMID:Cysteine conjugate beta-lyase activity in three species of parasitic helminth. 1042 30


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