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)

Astrocytes in primary culture possess a rapid L-aspartate saturable transport system (K(m) = 93 microM; V(max) = 81 nmol/min/mg protein), which shows certain stereospecificity since V(max) was 36% lower for D-aspartate uptake. These are values obtained at short incubation time (15 seconds), to obtain approximate initial rate conditions. Metabolic energy inhibitors, rotenone and iodoacetate very potently inhibited the L- and D-aspartate uptake processes, indicating that the transport process is an active one. However, the accumulation of L-aspartate was "enhanced" by inhibitors of L-aspartate metabolism, such as the aspartate aminotransferase inhibitor, aminooxyacetate and L-methionine sulfoximine, an inhibitor of glutamine synthetase, whereas D-aspartate (a non-metabolizable analog of L-aspartate) uptake was not affected. The accumulated levels of L-aspartate in the presence of aminooxyacetate were similar to the levels of D-aspartate. These effects of L-aspartate metabolic inhibitors, suggest that due to metabolism of the the L-aspartate, short incubation time (eg., 15 seconds) is necessary to measure the initial rate of L-aspartate uptake, in order to obtain the "true" kinetic parameters.
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PMID:The rapid L- and D-aspartate uptake in cultured astrocytes. 917 56

Cysteinyl-leukotrienes can cause cholestasis and liver damage when administered at nanomolar concentrations. Using the isolated and perfused rat liver we analyzed whether S-adenosyl-L-methionine (SAMe) may protect this organ against the noxious effects of leukotriene-D4 (LTD4). We observed that a 2 nmol bolus of this compound decreased bile flow (-12.6% +/- 1.6%, P < .02), and bile salt excretion (-23.5% +/- 2.2%, P < .02; both compared with baseline values), caused the release of glutamic-oxaloacetic transaminase (GOT) and lactic dehydrogenase (LDH) to the hepatic effluent, and increased significantly the perfusion pressure as compared with a control group not receiving LTD4 (6.0 +/- 1.1 vs. 0.2 +/- 0.02 mm hg, respectively; P < .001). The cholestatic effect of LTD4 was attenuated by infusion of SAMe which, at rates of 67 and 100 microg/min, totally prevented the decrease in bile salt excretion. Likewise, in SAMe infused livers, the release to the effluent of GOT and LDH was lower than in the group receiving LTD4 only, and was even lower than in the control group. We also found that the increase in perfusion pressure induced by LTD4 was prevented by SAMe in a dose-dependent manner. Of interest, SAMe increased the biliary excretion of the eicosanoid in a dose-related fashion. We conclude that SAMe reverts the cholestatic, cytotoxic, and hemodynamic effects of LTD4 on the liver, and that these protective effects might be partly because of a stimulation of the biliary excretion of the leukotriene.
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PMID:S-adenosyl-L-methionine protects the liver against the cholestatic, cytotoxic, and vasoactive effects of leukotriene D4: a study with isolated and perfused rat liver. 925 42

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

A new AAT allele (PI Zbristol) has been discovered in a woman with an obstetric history of three perinatal deaths from fulminant liver disease and no living offspring. She and her father were both PI M1Zbristol heterozygotes. The Zbristol protein is active as a proteinase inhibitor but appeared to be deficient in the plasma to about the same degree as the S protein in MS heterozygotes. It focuses on the basic side of Z and lacks the normal pattern of secondary isoforms associated with the commonly occurring AAT variants and migrates faster than normal on an SDS electrophoresis gel. The Zbristol mutation was found to be a C to T transition at codon 85 changing ACG (Thr) to ATG (Met). This disrupts the N-glycosylation site starting at Asn 83 preventing glycosylation at residue 83 in the PI Zbristol protein and explains the protein isoelectric focusing and SDS gel electrophoresis results. An analysis of haplotypes in the propositus and her father indicated that the Zbristol mutation occurred on the common M1(Val 213) genetic background. The new mutation also led to the generation of an NlaIII restriction endonuclease recognition site. Cell lines from two offspring tested for the presence of this NlaIII site revealed that one had the variant and the other did not. Thus, the relationship between Zbristol and fulminant liver disease in the offspring is unclear.
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PMID:A new alpha 1-antitrypsin mutation, Thr-Met 85, (PI Zbristol) associated with novel electrophoretic properties. 945

The effects of meso 2, 3-dimercaptosuccinic acid (DMSA), sodium 2, 3-dimercaptopropane 1-sulfonate (DMPS) and S-adenosyl L-methionine (SAM) on the enzymatic activities of mice were studied. The mice were given intraperitoneal (i.p.) injections of these chelating agents (1 mmol/kg) and 3 h later the activity of delta-aminolevulinic acid dehydratase (ALAD) in the blood, and aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltranspeptidase (gamma-GT), alkaline phosphatase (ALP) in the liver and kidney were determined. The activity of blood ALAD was significantly increased by the administration of DMSA and SAM while DMPS had only a moderate effect. The activities of other hepatic enzymes changed little when the mice were treated with these chelating agents, except for a significant reduction in hepatic ALP activity following DMPS administration. Arsenic (III) administration markedly increased the activities of ALT and ALP in the liver and kidneys. The changes in the enzymatic activities by treatment with arsenic were prevented by injection of DMSA, DMPS and SAM, DMSA being the most effective. These results indicate that DMSA, DMPS and SAM were not toxic to the liver or kidneys of mice and that treatment with DMSA is more effective than DMPS or SAM in protecting mice from acute hepatic or renal toxicity caused by arsenic.
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PMID:Effects of some thiol chelators on enzymatic activities in blood, liver and kidneys of acute arsenic (III) exposed mice. 955 1

Carbohydrates comprise about 50% of the mass of gp120, the external envelope glycoprotein of simian immunodeficiency virus (SIV) and human immunodeficiency virus. We identified 11 replication-competent derivatives of SIVmac239 lacking two, three, four, or five potential sites for N-linked glycosylation. These sites were located within and around variable regions 1 and 2 of the surface envelope protein of the virus. Asn (AAT) of the canonical N-linked glycosylation recognition sequence (Asn X Ser/Thr) was changed in each case to the structurally similar Gln (CAG or CAA) such that two nucleotide changes in the codon would be required for reversion. Replication of one triple mutant (g456), however, was severely impaired. A revertant of the g456 mutant was recovered from CEMx174 cells with a Met-to-Val compensatory substitution at position 144, 2 amino acids upstream of attachment site 5. Thus, a debilitating loss of sites for N-linked glycosylation can be compensated for by amino acid changes not involving the Asn-X-Ser/Thr consensus motif. These results provide a framework to begin testing the hypothesis that carbohydrates form a barrier that can limit the humoral immune responses to the virus.
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PMID:Identification of replication-competent strains of simian immunodeficiency virus lacking multiple attachment sites for N-linked carbohydrates in variable regions 1 and 2 of the surface envelope protein. 962 Sep 94

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

We investigated whether S-adenosyl-L-methionine (SAMe), dilinoleoylphosphatidylcholine (DLPC), or SAMe + DLPC influence liver lipid composition as well as acute ethanol hepatotoxicity in the isolated perfused rat liver (IPRL). SAMe (25 mg/kg intramuscularly three times a day) was administered for five consecutive days, while DLPC was administered intraperitoneally for five days. The liver was then isolated, perfused with taurocholate to stabilize bile secretion, and exposed to 0.5% ethanol for 70 min. SAMe, without changing total phospholipid (PL) content, induced an increase in the phosphatidylcholine/phosphatidylethanolamine (PC/PE) molar ratio in both liver homogenate and microsomes and a significant enrichment of 16:0-20:4 and 18:0-20:4 PC molecular species. DLPC induced a significant enrichment of PL in liver homogenate and microsomes due to a contemporary increase in PC and PE. The PC enrichment specifically involved 16:0-20:4 and 18:0-20:4 PC molecular species besides the HPLC peak containing the administered 18:2-18:2 PC species. DLPC + SAMe increased the concentration of PC in liver homogenate and microsomes due to a specific enrichment of 16:0-22:6, 16:0-20:4, and 18:0-20:4 PC molecular species, and the HPLC peak containing the administered 18:2-18:2 PC species. Ethanol acute exposure in the control IPRLs for 70 min induced a depletion of cholesterol in both liver homogenate and microsomes without significant changes in the composition of PL classes and PC molecular species. SAMe, DLPC, or SAMe + DLPC counteracted the cholesterol depletion induced by ethanol, indicating that phospholipid changes promoted by these treatments all induce a major resistance of liver membranes to the effect of ethanol. Ethanol administration in control IPRLs induced a fivefold increase of AST and LDH release in the perfusate, depletion of glutathione in homogenates and mitochondria, decreased oxygen liver consumption, and inhibition of bile flow. These effects of ethanol were significantly antagonized by SAMe. In contrast, DLPC alone only minimally attenuated enzyme release in the perfusate and the inhibitory effect of ethanol on bile flow, but it failed to influence the depletion of total and mitochondrial glutathione or the depressed oxygen consumption induced by ethanol. DLPC, administered together with SAMe, added nothing to the protective effect of SAMe against ethanol hepatotoxicity and cholestasis. In conclusion, this study demonstrates that both SAMe and DLPC induced marked modifications in the lipid composition of liver membranes with a similar enrichment of polyunsaturated PC molecular species. Only SAMe, however, significantly protected against the hepatotoxic and cholestatic effect of acute ethanol administration, an effect associated with maintained normal glutathione mitochondrial levels and oxygen liver consumption. This indicates that the protective effect of SAMe against ethanol toxicity is linked to multiple mechanisms, the maintenance of glutathione levels probably being one of the most important.
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PMID:Effect of S-adenosyl-L-methionine and dilinoleoylphosphatidylcholine on liver lipid composition and ethanol hepatotoxicity in isolated perfused rat liver. 979 Apr 56

Heptral (S-adenosine-L-methionine) was given to 32 patients with chronic diffuse diseases of the liver and intrahepatic cholestasis. 16 of them had primary biliary cirrhosis (PBC). Phase I of the treatment lasted 16 days when the drug was injected intravenously in a dose 800 mg/day. It was followed by phase 2--1600 mg/day taken for 16 days. A response was registered in the majority of patients. They had relieved symptoms of asthenia, skin pruritus, jaundice. The patients with liver cirrhosis and chronic hepatitis exhibited a statistically significant fall in ALT, AST and GGTP. PBS patients showed insignificant lowering of cholesterol, bilirubin. No resistance was noted in repeated courses. Heptral tolerance was satisfactory.
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PMID:[Clinical trial of heptral in patients with chronic diffuse liver disease with intrahepatic cholestasis syndrome]. 986 18

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


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