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)

Alanine transport and the role of alanine amino-transferase in the synthesis and consumption of glutamate were investigated in the preparation of rat brain synaptosomes. Alanine was accumulated rapidly via both the high- and low-affinity uptake systems. The high-affinity transport was dependent on the sodium concentration gradient and membrane electrical potential, which suggests a cotransport with Na+. Rapid accumulation of the Na(+)-alanine complex by synaptosomes stimulated activity of the Na+/K+ pump and increased energy utilization; this, in turn, activated the ATP-producing pathways, glycolysis and oxidative phosphorylation. Accumulation of Na+ also caused a small depolarization of the plasma membrane, a rise in [Ca2+]i, and a release of glutamate. Intra-synaptosomal metabolism of alanine via alanine amino-transferase, as estimated from measurements of N fluxes from labeled precursors, was much slower than the rate of alanine uptake, even in the presence of added oxoacids. The velocity of [15N]alanine formation from [15N]glutamine was seven to eight times higher than the rate of [15N]-glutamate generation from [15N]alanine. It is concluded that (a) overloading of nerve endings with alanine could be deleterious to neuronal function because it increases release of glutamate; (b) the activity of synaptosomal alanine aminotransferase is much slower than that of glutaminase and hence unlikely to play a major role in maintaining [glutamate] during neuronal activity; and (c) alanine amino-transferase might serve as a source of glutamate during recovery from ischemia/hypoxia when the alanine concentration rises and that of glutamate falls.
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PMID:Cerebral alanine transport and alanine aminotransferase reaction: alanine as a source of neuronal glutamate. 790 47

Pathophysiological concentrations of ammonia, both in vivo and in vitro, suppressed the oxidation of glutamate by rat cerebellar mitochondria. The transport of glutamate into mitochondria was either unaltered or enhanced during hyperammonemic states. Activities of mitochondrial enzymes, aspartate aminotransferase, alanine aminotransferase, glutamate dehydrogenase, glutaminase, and GABA-transaminase were suppressed during hyperammonemic states. Suppression of 14CO2 production with (aminooxy)acetic acid but not with glutamic acid diethyl ester indicated that transamination but not oxidative deamination of glutamate plays a major role in glutamate oxidation during normal and hyperammonemic states.
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PMID:Transport and metabolism of glutamate by rat cerebellar mitochondria during ammonia toxicity. 810 3

Gabapentin is a novel anticonvulsant drug. The anticonvulsant mechanism of gabapentin is not known. Based on the amino acid structure of gabapentin we explored its possible effects on glutamate and gamma-aminobutyric acid (GABA) metabolism in brain as they may relate to its anticonvulsant mechanisms of action. Gabapentin was tested for its effects on seven enzymes in the metabolic pathways of these two neurotransmitters: alanine aminotransferase (AL-T), aspartate aminotransferase (AS-T), GABA aminotransferase (GABA-T), branched-chain amino acid aminotransferase (BCAA-T), glutamine synthetase (Gln-S), glutaminase (GLNase), and glutamate dehydrogenase (GDH). In the presence of 10 mM gabapentin, only GABA-T, BCAA-T, and GDH activities were affected by this drug. Inhibition of GABA-T by gabapentin was weak (33%). The Ki values for inhibition of cytosolic and mitochondrial forms of GABA-T (17-20 mM) were much higher than the Km values for GABA (1.5-1.9 mM). It is, therefore, unlikely that inhibition of GABA-T by gabapentin is clinically relevant. As with leucine, gabapentin stimulated GDH activity. The GDH activity in rat brain synaptosomes was activated 6-fold and 3.4-fold, respectively, at saturating concentrations (10 mM) of leucine and gabapentin. The half-maximal stimulation by gabapentin was observed at approximately 1.5 mM. Gabapentin is not a substrate of BCAA-T, but it exhibited a potent competitive inhibition of both cytosolic and mitochondrial forms of brain BCAA-T. Inhibition of BCAA-T by this drug was reversible. The Ki values (0.8-1.4 mM) for inhibition of transamination by gabapentin were close to the apparent Km values for the branched-chain amino acids (BCAA) L-leucine, L-isoleucine, and L-valine (0.6-1.2 mM), suggesting that gabapentin may significantly reduce synthesis of glutamate from BCAA in brain by acting on BCAA-T.
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PMID:Effects of anticonvulsant drug gabapentin on the enzymes in metabolic pathways of glutamate and GABA. 856 62

Freshwater fish, Cyprinus carpio, was exposed to sublethal concentration (3 microg liter-1) of cypermethrin for 5 and 10 days to examine the changes in the transamination process during the formation of nitrogenous end products in four functionally different tissues, namely, gill, liver, brain, and muscle. Increases in total and soluble protein contents were noticed in all the tissues of exposed fish with a decrease in free amino acids and protease activity. Activity levels of both the transaminases, aspartate aminotransferase and alanine aminotransferase, and glutamate dehydrogenase were elevated, indicating active transamination and oxidative deamination. Attenuation of ammonia was consistent in both treatment groups. However, urea level decreased at the 5-day exposure period but increased by Day 10, manifesting the conversion of toxic ammonia to urea. Glutamine content was consistently raised upon exposure to the toxicant. In support of this, increases in glutamine synthetase and suppression of glutaminase were noticed. It clearly indicates that ammonia is not stored in the tissues in spite of active oxidative deamination when the fish is in a polluted environment. All the observations made demonstrate that the fish has adopted more than one compensatory mechanism during the process of transamination of nitrogenous products.
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PMID:Action of cypermethrin on tissue transamination during nitrogen metabolism in Cyprinus carpio. 881 84

Changes in the activity of enzymes involved in glutaminolysis and energy metabolism in the entire gastrointestinal (GI) tract of developing piglets are presented for the first time. The activities of glutaminase, glutamate dehydrogenase, oxoglutarate dehydrogenase, isocitrate dehydrogenase and alanine aminotransferase in the epithelium along the gastrointestinal tract from newborn, suckling (2-4 weeks old) and weaned (9 weeks old) piglets were investigated. The activity of glutaminase in the epithelium from the small intestine and colon was higher (p < 0.05) in weaned piglets than in newborn and suckling piglets. In addition, glutamate dehydrogenase and alanine aminotransferase activities in the small intestinal epithelium were higher (p < 0.05) for weaned piglets than for newborns. The activity of oxoglutarate dehydrogenase in the epithelium of the small intestine was significantly lower in newborn and suckling piglets compared with weaned individuals. The activity of isocitrate dehydrogenase in the epithelium along the gastrointestinal tract was higher (p < 0.05) for suckling and weaned piglets than for newborn piglets. The present data indicate that the utilization of substrates for energy production differs markedly between the stomach, small intestine and colon of growing piglets. Also, the capacity of enzymes in the epithelium of the GI tract to utilize acetyl-CoA as an energy substrate in the tricarboxylic acid cycle increased with piglet age. The epithelium of the GI tract of the newborn, suckling and weaned piglets showed a high capacity to metabolize alpha-ketoglutarate.
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PMID:Activities of enzymes involved in glutamine metabolism in connection with energy production in the gastrointestinal tract epithelium of newborn, suckling and weaned piglets. 1002 73

Changes in the activity of enzymes involved in oxidative metabolism of glutamine, and in protein content, in the epithelial tissue along the gastrointestinal (GI) tract of growing pigs exposed to nivalenol (NIV) in the diet were investigated. The epithelial tissue was taken from the stomach, small intestine and colon of three groups of animals fed diets without NIV (control), with inclusion of 2.5 mg NIV/kg diet (low dose) and with inclusion of 5.0 mg NIV/kg diet (high dose). The activities of glutaminase, glutamate dehydrogenase, oxoglutarate dehydrogenase, isocitrate dehydrogenase and alanine aminotransferase were determined. In the control pigs the activities of oxoglutarate dehydrogenase and alanine aminotransferase were higher (P < 0.05) in the epithelium of the small intestine as compared with the stomach and colon, while there were no differences in the activities of glutaminase, glutamate dehydrogenase and isocitrate dehydrogenase. With increasing inclusion of NIV in the diet the activity of oxoglutarate dehydrogenase decreased (P < 0.05) in the epithelium of the small intestine and colon, and the activity of alanine aminotransferase tended (P = 0.07) to increase in the epithelium of the small intestine. The activities of glutaminase, glutamate dehydrogenase and isocitrate dehydrogenase remained unaffected by the inclusion of NIV in the diet. In the control pigs the protein content in the epithelium of the small intestine was higher (P < 0.05) than in the stomach and colon, while there were no effects of NIV inclusion in the diet on the protein content. It can be concluded from the present study that the epithelial tissue of the small intestine and colon of pigs exposed to a diet containing NIV will have a reduced enzymatic capacity to utilise alpha-ketoglutarate in the tricarboxylic acid cycle (TCA-cycle), suggesting an impaired energy supply to these organs.
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PMID:Effect of exposure to dietary nivalenol on activity of enzymes involved in glutamine catabolism in the epithelium along the gastrointestinal tract of growing pigs. 1055 90

Glutamine plays a vital role in fetal carbon and nitrogen metabolism and exhibits the highest fetal:maternal plasma ratio among all amino acids in pigs. Such disparate glutamine levels between mother and fetus suggest that glutamine may be actively synthesized and released into the fetal circulation by the porcine placenta. We hypothesized that branched-chain amino acid (BCAA) metabolism in the placenta plays an important role in placental glutamine synthesis. This hypothesis was tested by studying conceptuses from gilts on Days 20, 30, 35, 40, 45, 50, 60, 90, or 110 of gestation (n = 6 per day). Placental tissue was analyzed for amino acid concentrations, BCAA transport, BCAA degradation, and glutamine synthesis as well as the activities of related enzymes (including BCAA transaminase, branched-chain alpha-ketoacid dehydrogenase, glutamine synthetase, glutamate-pyruvate transaminase, and glutaminase). On all days of gestation, rates of BCAA transamination were much greater than rates of branched-chain alpha-ketoacid decarboxylation. The glutamate generated from BCAA transamination was primarily directed to glutamine synthesis and, to a much lesser extent, alanine production. Placental BCAA transport, BCAA transamination, glutamine synthesis, and activities of related enzymes increased markedly between Days 20 and 40 of gestation, as did glutamine in fetal allantoic fluid. Accordingly, placental BCAA levels decreased after Day 20 of gestation in association with a marked increase in BCAA catabolism and concentrations of glutamine. There was no detectable catabolism of glutamine in pig placenta throughout pregnancy, which would ensure maximum output of glutamine by this tissue. These novel results demonstrate glutamine synthesis from BCAAs in pig placentae, aid in explaining the abundance of glutamine in the fetus, and provide valuable insight into the dynamic role of the placenta in fetal metabolism and nutrition.
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PMID:Glutamine synthesis in the developing porcine placenta. 1473 17

An amino acid-based solution has been recently developed and has demonstrated significant protective effects during cold storage of small bowel (SB). This study was designed to examine the role of this novel solution in ameliorating intestinal injury in an in vivo model of ischemia-reperfusion (IR). The impact of luminal treatment with an amino acid-based (AA) solution was assessed throughout reperfusion after 60-min warm ischemia (WI) in rodent SB. Energetics (ATP and total adenylates) remained significantly elevated throughout 60-min reperfusion in AA-treated tissue compared with untreated controls. Increases in end-products (ammonia and alanine) and increases in alanine aminotransferase and glutaminase activity implicated greater amino acid metabolism in AA-treated tissues. After reperfusion, malondialdehyde levels were similar between all groups. Glutathione levels were consistently elevated in AA-treated tissues and by 60 min reperfusion values were sixfold greater than control. AA-mediated protection during IR resulted in reduced neutrophil infiltration suggesting a weaker inflammatory response. Barrier function and electrophysiology parameters exhibited a clear pattern of mucosal preservation in AA-treated tissues; histology supported these findings. This study raises the possibility of a role for a luminal nutrient-rich solution during ischemic storage of small bowel in the clinic.
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PMID:Alleviating ischemia-reperfusion injury in small bowel. 1508 67

We have studied the effect of the pyruvate dehydrogenase (PDH) activator, dichloroacetate (DCA), on the growth, metabolism, and productivity of the PQXB (1/2) hybridoma cell line. In control batch cultures, cessation of growth and the onset of decline phase coincided with the time at which the media became exhausted of glutamine. Supplementation of the media with DCA (1 mM) extended the growth phase of this cell line by approximately 20 h without affecting its growth rate. This prolonged period of growth resulted in an increased maximum cell density (16%) and final antibody yield (55%). Repeat experiments showed these effects to be reproducible, with the increases in antibody yield being between 50 and 60%. DCA did not affect the specific rates of glucose utilization and lactate production. However, it decreased the specific glutamine consumption rate. This characteristic of DCA action appeared, at least in part, to provide an explanation for the extended growth phase exhibited by DCA-treated cultures, since it delayed the time at which the media became depleted of glutamine. The consumption and production kinetics for various nutrients and their metabolites in both control and DCA-treated cultures suggested that: (1) glutamine catabolism proceeded by a pathway involving conversion to glutamate by glutaminase followed by subsequent transamination by alanine aminotransferase, and (2) DCA decreased the specific glutamine consumption rate by directly or indirectly inhibiting the transamination. It is expected that the routine inclusion of DCA in media used for hybridoma cultivation will be valuable for enhancement of monoclonal antibody (Mab) yields on a laboratory scale. (c) 1996 John Wiley & Sons, Inc.
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PMID:Dichloroacetate increases cell and antibody yields in batch cultures of a hybridoma cell line. 1862 91

Hypoglycemic coma caused by insulin injection to rats with alloxan-induced diabetes was accompanied by an increase in the concentrations of urea and uric acid and decrease in the content of free amino acids in blood plasma. Activities of glutamate dehydrogenase, AMP deaminase, glutaminase, ALT, and AST in the liver of experimental animals increased.
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PMID:Parameters of nitrogen metabolism during insulin hypoglycemia in rats with alloxan-induced diabetes. 1914 18


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