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

Quinidine in vitro significantly reduced accumulation of TEA (tetraethyl ammonium) and PAH (p-amino hippurate) and inhibited oxygen consumption in renal cortical slices. Mitochondrial respiratory control index (RCI) and ADP/O ratio were decreased. Intraperitoneal administration of quinidine at 75 mg/kg twice a day for four days inhibited TEA transport in renal cortical slices and decreased oxygen consumption. Mitochondria showed a reduction in ADP/O ratio but no change in RCI. Serum biochemical measurements indicated a significant elevation in serum creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST).
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PMID:In vitro and in vivo effects of quinidine on the kidneys in Fischer-344 rats. 830 84

The anaerobic fungus Piromyces sp. strain E2 appeared restricted in nitrogen utilization. Growth was only supported by ammonium as source of nitrogen. Glutamine also resulted in growth, but this was due to release of ammonia rather than to uptake and utilization of the amino acid. The fungus was not able to grow on other amino acids, albumin, urea, allantoin, or nitrate. Assimilation of ammonium is very likely to be mediated by NADP-linked glutamate dehydrogenase (NADP-GDH) and glutamine synthetase (GS). One transaminating activity, glutamate-oxaloacetate transaminase (GOT), was demonstrated. Glutamate synthase (GOGAT), NAD-dependent glutamate dehydrogenase (NAD-GDH), and the transaminating activity glutamate-pyruvate transaminase (GPT) were not detected in cell-free extracts of Piromyces sp. strain E2. Specific enzyme activities of both NADP-GDH and GS increased four- to sixfold under nitrogen-limiting conditions.
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PMID:The anaerobic fungus Piromyces sp. strain E2: nitrogen requirement and enzymes involved in primary nitrogen metabolism. 908 17

The idea of a metabolic coupling between neurons and astrocytes in the brain has been entertained for about 100 years. The use recently of simple and well-compartmentalized nervous systems, such as the honeybee retina or purified preparations of neurons and glia, provided strong support for a nutritive function of glial cells: glial cells transform glucose to a fuel substrate taken up and used by neurons. Particularly, in the honeybee retina, photoreceptor-neurons consume alanine supplied by glial cells and exogenous proline. NH4+ and glutamate are transported into glia by functional plasma membrane transport systems. During increased activity a transient rise in the intraglial concentration of NH4+ or of glutamate causes a net increase in the level of reduced nicotinamide adenine dinucleotides [NAD(P)H]. Quantitative biochemistry showed that this is due to activation of glycolysis in glial cells by the direct action of NH4+ and of glutamate, probably on the enzymatic reactions controlled by phosphofructokinase alanine aminotransferase and glutamate dehydrogenase. This activation leads to a massive increase in the production and release of alanine by glia. This constitutes an intracellular signal and it depends upon the rate of conversion of NH4+ and of glutamate to alanine and alpha-ketoglutarate, respectively, in the glial cells. Alanine and alpha-ketoglutarate are released extracellularly and then taken up by neurons where they contribute to the maintenance of the mitochondrial redox potential. This signaling raises the novel hypothesis of a tight regulation of the nutritive function of glia.
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PMID:The nutritive function of glia is regulated by signals released by neurons. 929 50

Axenic mycelia of the ectomycorrhizal basidiomycete, Suillus bovinus, were grown in liquid media under continuous aeration with compressed air at 25 degrees C in darkness. Provided with glucose as the only carbohydrate source, they produced similar amounts of dry weight with ammonia, with nitrate or with alanine, 60-80% more with glutamate or glutamine, but about 35% less with urea as the respectively only exogenous nitrogen source. In crude extracts of cells from NH4(+)-cultures, NADH-dependent glutamate dehydrogenase exhibited high aminating (688 nmol x mg protein(-1) x min(-1)) and low deaminating (21 nmol x mg protein(-1) x min(-1)) activities. Its Km-values for 2-oxoglutarate and for glutamate were 1.43 mM and 23.99 mM, respectively. pH-optimum for amination was about 7.2, that for deamination about 9.3. Glutamine synthetase activity was comparatively low (59 nmol x mg protein(-1) x min(-1)). Its affinity for glutamate was poor (Km = 23.7 mM), while that for the NH4+ replacing NH2OH was high (Km = 0.19 mM). pH-optimum was found at 7.0. Glutamate synthase (= GOGAT) revealed similar low activity (62 nmol x mg protein(-1) x min(-1)), Km-values for glutamine and for 2-oxoglutarate of 2.82 mM and 0.28 mM, respectively, and pH-optimum around 8.0. Aspartate transaminase (= GOT) exhibited similar affinities for aspartate (Km = 2.55 mM) and for glutamate (Km = 3.13 mM), but clearly different Km-values for 2-oxoglutarate (1.46 mM) and for oxaloacetate (0.13 mM). Activity at optimum pH of about 8.0 was 506 nmol x mg protein(-1) x min(-1) for aspartate conversion, but only 39 nmol x mg protein(-1) x min(-1) at optimum pH of about 7.0 for glutamate conversion. Activity (599 nmol x mg protein(-1) x min(-1)), substrate affinities (Km for alanine = 6.30 mM, for 2-oxoglutarate = 0.45 mM) and pH-optimum (6.5-7.5) proved alanine transaminase (= GPT) also important in distribution of intracellular nitrogen. There was comparatively low activity of the obviously constitutive enzyme, urease, (42 nmol x mg protein(-1) x min(-1)) whose substrate affinity was rather high (Km = 0.56 mM). Nitrate reductase proved substrate induced; activity could only be measured after exposure of the mycelia to exogenous nitrate. Routes of entry of exogenous nitrogen and tentative significance of the various enzymes in cell metabolism are discussed.
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PMID:Investigations into enzymes of nitrogen metabolism of the ectomycorrhizal basidiomycete, Suillus bovinus. 1081 9

Troglitazone is a peroxisome proliferator-activated receptor-gamma agonist that has been shown to halt mesangium expansion in experimental models of type 2 diabetes mellitus and to act directly on rat mesangial cells. Because glutamine serves as the precursor for cellular biosynthetic processes, we asked whether troglitazone would inhibit mesangial cell glutamine metabolism under these conditions. Confluent monolayers of rat mesangial cells were incubated in RPMI medium in the presence of troglitazone or vehicle (DMSO). Troglitazone effected a dose-dependent reduction in glutamine utilization and in alanine formation, associated with a decrease in monolayer collagen-glycosaminoglycan content. Despite the reduced glutamine uptake, ammonium formation did not decrease, consistent with increased glutamate flux through the deamination pathway. Assayable activity of the alanine aminotransferase decreased by 63%, whereas assayable glutamate dehydrogenase remained unchanged. In control monolayers, the sum of ammonium plus alanine plus glutamate nitrogen released accounted for <75% of the glutamine nitrogen uptake. In troglitazone-treated monolayers, all of the glutamine nitrogen taken up could be accounted for as ammonium nitrogen released into the medium. These results are consonant with troglitazone reducing glutamine metabolism and specifically the transamination pathway in rat mesangial cells associated with a reduction in collagen-glycosaminoglycan content.
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PMID:Troglitazone inhibits glutamine metabolism in rat mesangial cells. 1173 5

We studied the effect of the antihyperglycemic glitazones, ciglitazone, troglitazone, and rosiglitazone, on glutamine metabolism in renal tubule-derived Madin-Darby canine kidney (MDCK) cells. Troglitazone (25 microM) enhanced glucose uptake and lactate production by 108 and 92% (both P < 0.001). Glutamine utilization was not inhibited, but alanine formation decreased and ammonium formation increased (both P < 0.005). The decrease in net alanine formation occurred with a change in alanine aminotransferase (ALT) reactants, from close to equilibrium to away from equilibrium, consistent with inhibition of ALT activity. A shift of glutamine's amino nitrogen from alanine into ammonium was confirmed by using L-[2-(15)N]glutamine and measuring the [(15)N]alanine and [(15)N]ammonium production. The glitazone-induced shift from alanine to ammonium in glutamate metabolism was dose dependent, with troglitazone being twofold more potent than rosiglitazone and ciglitazone. All three glitazones induced a spontaneous cellular acidosis, reflecting impaired acid extrusion in responding to both an exogenous (NH) and an endogenous (lactic acid) load. Our findings are consistent with glitazones inducing a spontaneous cellular acidosis associated with a shift in glutamine amino nitrogen metabolism from predominantly anabolic into a catabolic pathway.
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PMID:Glitazones regulate glutamine metabolism by inducing a cellular acidosis in MDCK cells. 1221 90

The potential sensitivity of liver specific protein regucalcin as a biochemical marker of chronic liver injury with carbon tetrachloride (CCl4) administration in rats was investigated. CCl4 (10%; 1.0 ml/100 g body wt) was orally given 5 times at 3-day intervals to rats, and the animals were killed by bleeding at 3, 6, 18, and 30 days after the first administration of CCl4. The body weight of rats was significantly lowered 3 and 6 days after CCI4 administration as compared with that of control rats administered with corn oil, and then the weight was restored at 18 and 30 days. Serum glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) activities were significantly increased 3 days after the administration, while a significant increase in serum y-glutamyltranspeptidase (gamma-GTP) activity was seen at 3 and 6 days after the administration. Serum GOT, GPT, and gamma-GTP activities were restored to control levels at 18 and 30 days after CCl4 administration. Serum albumin, alpha-fetoprotein, and ammonium levels were not changed by CCl4 administration. Meanwhile, serum regucalcin concentration was markedly increased 3 and 6 days after CCl4 administration, and a significant increase in serum regucalcin concentration was observed 18 and 30 days after the administration. Liver regucalcin mRNA and liver cytosolic regucalcin levels were significantly decreased 18 and 30 days after CCl4 administration. Liver content of calcium, which intracellular calcium homeostasis is maintained, was significantly increased between 3 and 30 days after CCl4 administration. Hepatic mitochondrial succinate dehydrogenase activity was significantly increased 30 days after the administration. The present study demonstrates that serum regucalcin has a potential sensitivity as a specific biochemical marker of chronic liver injury with CCl4 administration in rats.
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PMID:Potential role of regucalcin as a specific biochemical marker of chronic liver injury with carbon tetrachloride administration in rats. 1248 26

The metabolism of [1-13C]glucose in the vegetative mycelium of the ectomycorrhizal ascomycete Tuber borchii was studied in order to characterize the biochemical pathways for the assimilation of glucose and amino acid biosynthesis. The pathways were characterized using nuclear magnetic resonance spectroscopy in conjunction with [1-13C]glucose labeling. The enzymes of mannitol cycle and ammonium assimilation were also evaluated. The majority of the 13C label was incorporated into mannitol and this polyol was formed via a direct route from absorbed glucose. Amino acid biosynthesis was also an important sink of assimilated carbon and 13C was mainly incorporated into alanine and glutamate. From this intramolecular 13C enrichment, it is concluded that pyruvate, arising from [1-13C]glucose catabolism, was used by alanine aminotransferase, pyruvate dehydrogenase and pyruvate carboxylase before entering the Krebs cycle. The transfer of 13C-labeled mycelium on [12C]glucose showed that mannitol, alanine, and glutamate carbon were used to synthesize glutamine and arginine that likely play a storage role.
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PMID:Carbohydrate and amino acid metabolism in Tuber borchii mycelium during glucose utilization: a (13)C NMR study. 1278 75

Intravenous administration of glycyrrhizin has potential efficacy on decreasing serum aminotransferase levels in patients with chronic hepatitis. However, patients receiving this treatment are recommended to attend hospital regularly for several years. To improve the quality of life for these patients, we developed a glycyrrhizin suppository. In this pilot study, we examined the most effective and safe material contents of the suppository and revealed clinical efficacy for patients with biopsy-proven chronic hepatitis C comparing intravenous administration of glycyrrhizin. As content combinations of the suppository, a mixture of 300 mg of glycyrrhizinic ammonium salt and 60 &mgr;g of sodium capric acid, with pH neutralization, was confirmed to be most effective and safe condition, based on analysis of serum glycyrrhizin levels and the grade of rectal irritations in tested patients. The efficacy on decreasing serum alanine aminotransferase levels for 12-week administration of the suppository in 13 patients with chronic hepatitis C was similar to that in another 13 patients intravenously administered glycyrrhizin. Moreover, no serious side effects were observed. In conclusion, the usage of the newly developed suppository of glycyrrhizin can improve the quality of life for chronic hepatitis C patients, especially those who do not respond with viral clearance to interferon therapy. Using this suppository, larger and longer-term studies are needed.
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PMID:Efficacy of a glycyrrhizin suppository for the treatment of chronic hepatitis C: a pilot study. 1278 98

The dry weight, total N, and glutamate-oxaloacetate transaminase(GOT) and glutamate-pyruvate transaminase (GPT) activities in roots and leaves of wheat seedlings (Triticum aestivum) grown with ammonium sulfate or amino acids (glycine, glutamate or lysine) were studied under sterile sand culture. The results showed that both NH4(+)-N and amino acid-N could be absorbed by wheat. The total N of plant fed with NH4(+)-N was similar to that fed with amino acid-N. The dry weight of plants grown 30 days with glycine or glutamate was significantly higher than that of plants grown with NH4(+)-N or free N. The dry weight of ammonium treatment was similar to that of lysine treatment or free N. NH4(+)-N in concentration of 0.7 mmol.L-1 significantly increased GPT activity of roots, but had no significant effects on leaves or roots treated 6 h in concentration of 35.7 mmol.L-1. Different species or concentrations of amino acids had different abilities to increase the GOT or GPT activity in leaves or roots.
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PMID:[Effects of amino acid-N and ammonium-N on wheat seedlings under sterile culture]. 1282 67


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