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:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Factors regulating the release of alanine and glutamine in vivo were investigated in starved rats by removing the liver from the circulation and monitoring blood metabolite changes for 30 min. 2. Alanine and glutamine were the predominant amino acids released into the circulation in this preparation. 3. Dichloroacetate, an activator of pyruvate dehydrogenase, inhibited net alanine release: it also interfered with the metabolism of the branched-chain amino acids valine, leucine and isoleucine. 4. L-Cycloserine, an inhibitor of alanine aminotransferase, decreased alanine accumulation by 80% after functional hepatectomy, whereas methionine sulphoximine, an inhibitor of glutamine synthetase, decreased glutamine accumulation by the same amount. 5. It was concluded that: (a) the alanine aminotransferase and the glutamine synthetase pathways respectively were responsible for 80% of the alanine and glutamine released into the circulation by the extrasplanchnic tissues, and extrahepatic proteolysis could account for a maximum of 20%; (b) alanine formation by the peripheral tissues was dependent on availability of pyruvate and not of glutamate; (c) glutamate availability could influence glutamine formation subject, possibly, to renal control.
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PMID:Factors regulating amino acid release from extrasplanchnic tissues in the rat. Interactions of alanine and glutamine. 0 55

The levels of L-lactate and pyruvate as well as the enzymes of their conversion (lactate dehydrogenase in direct and reverse reactions, pyruvate dehydrogenase, pyruvate kinase, alanine transaminase) have been studied simultaneously in the liver and skeletal muscle of rats bearing carcinosarcoma Walker 256, control animals and after additional oxythiamine administration. Properties of oxythiamine independent of its anticoenzymic activity manifest themselves in the body of tumour-bearing animals to a greater extent. After the antivitamin administration there occur strong inhibition of pyruvate kinase, activation of alanine transaminase, normalization of the L-lactate level in the tissues.
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PMID:[Lactate and pyruvate metabolism in the tissues of rats with Walker carcinosarcoma injected with oxythiamine]. 651 Mar 36

1. The metabolism of L-alanine was studied in isolated guinea-pig kidney-cortex tubules. 2. In contrast with previous conclusions of Krebs [(1935) Biochem. J. 29, 1951-1969], glutamine was found to be the main carbon and nitrogenous product of the metabolism of alanine (at 1 and 5 mM). Glutamate and ammonia were only minor products. 3. At neither concentration of alanine was there accumulation of glucose, glycogen, pyruvate, lactate, aspartate or tricarboxylic acid-cycle intermediates. 4. Carbon-balance calculations and the release of 14CO2 from [U-14C]alanine indicate that oxidation of the alanine carbon skeleton occurred at both substrate concentrations. 5. A pathway involving alanine aminotransferase, glutamate dehydrogenase, glutamine synthetase, pyruvate dehydrogenase, pyruvate carboxylase and enzymes of the tricarboxylic acid cycle is proposed for the conversion of alanine into glutamine. 6. Strong evidence for this pathway was obtained by: (i) suppressing alanine removal by amino-oxyacetate, and inhibitor of transaminases, (ii) measuring the release of 14CO2 from [1-14C]alanine, (iii) the use of L-methionine DL-sulphoximine, an inhibitor of glutamine synthetase, which induced a large increase in ammonia release from alanine, and (iv) the use of fluoroacetate, an inhibitor of aconitase, which inhibited glutamine synthesis with concomitant accumulation of citrate from alanine. 7. In this pathway, the central role of pyruvate carboxylase, which explains the discrepancy between our results and those of Krebs (1935), was also demonstrated.
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PMID:The conversion of alanine into glutamine in guinea-pig renal cortex. Essential role of pyruvate carboxylase. 733 38

Everyday administration of citrate (250 mg/kg of body mass) into healthy rats within 4 days inhibited activities of pyruvate kinase, pyruvate dehydrogenase, alanine transaminase and of reverse lactate dehydrogenase in liver tissue but not in sceletal muscles. Within the longer period of citrate administration (8 or 12 days) activities of pyruvate dehydrogenase and alanine transaminase continued to decrease in liver tissue, at the same time, content of pyruvate proceeded to increase in sceletal muscles. More distinct inhibitory effect of citrate on the pyruvate dehydrogenase activity was observed not only in liver tissue but and in sceletal muscles of tumor-bearing animals. Alanine transaminase, which was inactivated in liver tissue of healthy animals after citrate treatment, was markedly activated in tumor-bearing rats in the same conditions. The data obtained suggest that some regulatory functions of citrate were qualitatively transformed in tumor-bearing animals, mainly, in relation to turnover of glucogenic amino acids.
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PMID:[Features of pyruvate and lactate metabolism in tumor-bearing rats following citrate administration]. 746 8

In the adipose tissue, besides fatty acid synthesis (FA-S) from glucose, which includes several mitochondrial steps, FA-S from glutamate has been demonstrated. FA-S from glutamate takes place in the cytosol through the backward pathway of Krebs cycle (BPKC) and is due to the sequential action of (1) alanine aminotransferase (ALT, EC 2.6.1.2), which is presence of pyruvate converts glutamate to oxoglutarate; (2) isocitrate dehydrogenase (NADP) (ICDH, EC 1.1.1.42), which converts oxoglutarate to isocitrate; (3) aconitate hydratase (ACO, EC 4.2.1.3), which transforms isocitrate to citrate: and (4) ATP citrate-lyase (ATP-CL, EC 4.1.3.8), which splits citrate to yield the acetyl-CoA needed for FA-S. We studied the enzymes involved in BPKC in homogenates of human adipose tissue. In normal subjects, the cytosolic activity (mumol/min/g protein) was: ALT = 10.3 +/- 1.1, ICDH = 29.5 +/- 2.8, ACO = 2.05 +/- 0.23, and ATP-CL = 1.2 +/- 0.2. Mitochondria contained less or no activity, values being 20, 9, 11, and 0% of total for ATL, ICDH, ACO, and ATP-CL, respectively. BPKC enzymes are more active than the enzymes limiting FA-S from glucose, i.e., phosphofructokinase (EC 2.7.1.11), pyruvate carboxylase (EC 6.4.1.1), and pyruvate dehydrogenase (EC 1.2.4.1). In the obese patients, cytosolic ALT and ATP-CL were increased (12.9 +/- 0.7, P < 0.05, and 2.28 +/- 0.27, P < 0.01, respectively) compared to normal, while ICDH was not changed (ACO could not be studied). Similar changes were obtained by expressing enzyme activity per fat cell number.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fatty acid synthesis from glutamate in the adipose tissue of normal subjects and obese patients: an enzyme study. 755 12

The rabbit kidney does not readily metabolize but synthesizes glutamine at high rates by pathways that remain poorly defined. Therefore, the metabolism of variously labeled [13C]- and [14C]glutamates has been studied in isolated rabbit kidney tubules with and without acetate. CO2, glutamine, and alanine were the main carbon and nitrogenous end products of glutamate metabolism but no ammonia accumulated. Absolute fluxes through enzymes involved in glutamate metabolism, including enzymes of four different cycles operating simultaneously, were assessed by combining mainly the 13C NMR data with a new model of glutamate metabolism. In contrast to a previous conclusion of Klahr et al. (Klahr, S., Schoolwerth, A. C., and Bourgoignie, J. J. (1972) Am. J. Physiol. 222, 813-820), glutamate metabolism was found to be initiated by glutamate dehydrogenase at high rates. Glutamate dehydrogenase also operated at high rates in the reverse direction; this, together with the operation of the glutamine synthetase reaction, masked the release of ammonia. Addition of acetate stimulated the operation of the "glutamate --> alpha-ketoglutarate --> glutamate" cycle and the accumulation of glucose but reduced both the net oxidative deamination of glutamate and glutamine synthesis. Acetate considerably increased flux through alpha-ketoglutarate dehydrogenase and citrate synthase at the expense of flux through phosphoenolpyruvate carboxykinase; acetate also caused a large decrease in flux through alanine aminotransferase, pyruvate dehydrogenase, and the "substrate cycle" involving oxaloacetate, phosphoenolpyruvate, and pyruvate.
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PMID:The rabbit kidney tubule simultaneously degrades and synthesizes glutamate. A 13C NMR study. 903 May 22

The metabolism of pyruvate by Campylobacter spp. was investigated employing one- and two-dimensional 1H, 13C and 31P nuclear magnetic resonance spectroscopy. Metabolically competent cells incubated aerobically with pyruvate yielded acetate, acetolactate, alanine, formate, lactate, and succinate. The production of acetolactate, alanine and lactate indicated the presence of acetohydroxy acid synthase, alanine transaminase and lactate dehydrogenase activities, respectively. Accumulation of acetate and formate as metabolic products provided evidence for the existence of a mixed acid fermentation pathway in the microorganism. Formation of succinate suggested the incorporation of the pyruvate carbon skeleton to the Kreb's cycle, and the observation of pyruvate dehydrogenase activities in bacterial lysates supported this interpretation. Generation of pyruvate from L-serine in incubations with intact cells and lysates indicated the presence of serine dehydratase activity in the bacterium. Pyruvate was also formed in cell suspensions and lysates from phosphoenol pyruvate. The existence of anaplerotic sequences involving phosphoenol pyruvate carboxykinase and a malic enzyme were established in bacterial lysates. The activities of enzymes involved in the biosynthesis of isoleucine and valine were measured. Addition of pyruvate to different solid culture media inhibited bacterial growth, and the inhibition was attributed to the accumulation of acetate and formate. The variety of products formed using pyruvate as the sole substrate and the existence of anaplerotic sequences and anabolic pathways which employ pyruvate, showed the important role of this metabolite in the energy and biosynthesis metabolism of Campylobacter spp.
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PMID:Pyruvate metabolism in Campylobacter spp. 910 25

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

A significant problem faced by pharmaceutical companies today is the failure of lead compounds in the later stages of development due to unexpected toxicities. We have used two-dimensional differential in-gel electrophoresis and mass spectrometry to identify a proteomic signature associated with hepatocellular steatosis in rats after dosing with a compound in preclinical development. Liver toxicity was monitored over a 5 day dosing regime using blood biochemical parameter measurements and histopathological analysis. As early as 6 h postdosing, livers showed hepatocellular vacuolation, which increased in extent and severity over the course of the study. Alterations in plasma glucose, alanine aminotransferase, and aspartate aminotransferase were not detected until the third day of dosing and changed in magnitude up to the final day. The proteomic changes were observed at the earliest time point, and many of these could be associated with known toxicological mechanisms involved in liver steatosis. This included up-regulation of pyruvate dehydrogenase, phenylalanine hydroxylase, and 2-oxoisovalerate dehydrogenase, which are involved in acetyl-CoA production, and down-regulation of sulfite oxidase, which could play a role in triglyceride accumulation. In addition, down-regulation of the chaperone-like protein, glucose-regulated protein 78, was consistent with the decreased expression of the secretory proteins serum paraoxonase, serum albumin, and peroxiredoxin IV. The correlation of these protein changes with the clinical and histological data and their occurrence before the onset of the biochemical changes suggest that they could serve as predictive biomarkers of compounds with a propensity to induce liver steatosis.
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PMID:A proteomic investigation of drug-induced steatosis in rat liver. 1514 17

Nuclear magnetic resonance spectroscopy was utilized to study the metabolism of [1-(13)C]glucose in mycelia of the ectomycorrhizal ascomycete Sphaerosporella brunnea. The main purpose was to assess the biochemical pathways for the assimilation of glucose and to identify the compounds accumulated during glucose assimilation. The majority of the (13)C label was incorporated into mannitol, while glycogen, trehalose and free amino acids were labeled to a much lesser extent. The high enrichment of the C1/C6 position of mannitol indicated that the polyol was formed via a direct route from absorbed glucose. Randomization of the (13)C label was observed to occur in glucose and trehalose leading to the accumulation of [1,6-(13)C]trehalose and [1,6-(13)C]glucose. This suggests that the majority of the glucose carbon used to form trehalose was cycled through the metabolically active mannitol pool. The proportion of label entering the free amino acids represented 38% of the soluble (13)C after 6 hours of continuous glucose labeling. Therefore, amino acid biosynthesis is an important sink of assimilated carbon. Carbon-13 was incorporated into [3-(13)C]alanine and [2-(13)C]-, [3-(13)C]-, and [4-(13)C]glutamate and glutamine. From the analysis of the intramolecular (13)C enrichment of these amino acids, it is concluded that [3-(13)C]pyruvate, arising from [1-(13)C]glucose catabolism, was used by alanine aminotransferase, pyruvate dehydrogenase, and pyruvate carboxylase (or phosphoenolpyruvate carboxykinase). Intramolecular (13)C labeling patterns of glutamate and glutamine were similar and are consistent with the operation of the Krebs cycle. There is strong evidence for (a) randomization of the label on C2 and C3 positions of oxaloacetate via malate dehydrogenase and fumarase, and (b) the dual biosynthetic and respiratory role of the citrate synthase, aconitase, and isocitrate dehydrogenase reactions. The high flux of carbon through the carboxylation (presumably pyruvate carboxylase) step indicates that CO(2) fixation is an important component of the carbon metabolism in S. brunnea, and it is likely that this anaplerotic role is particularly prevalent during NH(4) (+) assimilation. The most relevant information resulting from this investigation is (a) the occurrence of the mannitol cycle, (b) a large part of the trehalose pool is synthesized after the cycling of glucose-carbon through the mannitol cycle, and (c) pyruvate (or phosphoenolpyruvate) carboxylation plays an important role in the primary metabolism of glucose-fed mycelia.
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PMID:Carbohydrate and Amino Acid Metabolism in the Ectomycorrhizal Ascomycete Sphaerosporella brunnea during Glucose Utilization : A C NMR Study. 1666 12


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