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)

Nitric oxide synthase produces NO, citrulline, water, and NADP at the expense of arginine, NADPH, and dioxygen. While citrulline has been considered to be an inert by-product of the high output inducible isoform of NO synthase (iNOS), we show here that immunostimulants induce a metabolic pathway in vascular smooth muscle cells, which enables them to regenerate arginine from citrulline. Regeneration of arginine from citrulline is accomplished by two urea cycle enzymes: arginino-succinate synthetase (AS) and argininosuccinate lyase (AL). Whereas AL is constitutive to vascular smooth muscle cells, AS mRNA and enzyme activity is markedly induced in cells by treatment with bacterial lipopolysaccharide (LPS). The induction of AS mRNA and activity by LPS follows a time course which mirrors that for iNOS but lags 1-2 h behind. As shown for iNOS, interferon-gamma does not itself induce AS but is synergistic with LPS. AS induction is suppressed by glucocorticoids, actinomycin D, and, to a lesser extent, cycloheximide. On the other hand, AS induction is unaffected by an excess of citrulline or the inhibitor of iNOS, N omega-methyl-L-arginine. Our results show the urea cycle enzymes AS and AL confer cells with the capacity to produce NO without a need for exogenous arginine. In conjunction with NOS, citric acid cycle enzymes that covert fumarate to oxaloacetate (fumarase and malate dehydrogenase) and oxaloacetate to aspartate (aspartate transaminase), AS and AL form a novel arginine-citrulline cycle that enables high output NO production by cells.
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PMID:Argininosuccinate synthetase mRNA and activity are induced by immunostimulants in vascular smooth muscle. Role in the regeneration or arginine for nitric oxide synthesis. 751 85

Weiss et al. (Circ. Res. 70: 392-408, 1992) proposed a model of the citric acid cycle (CAC) in myocytes and a system of 17 differential equations that can be used to describe the changes over time in enrichment of carbons C-2 and C-4 of glutamate under conditions of metabolic steady state. They also proposed an empirical measure (KT) of flux through the CAC, which has been shown to be correlated to O2 consumption in rat hearts perfused with acetate or a mixture of glucose and acetate. We report a new method for estimation of the absolute rate of the flux through the CAC in heart (vTCA), without the numerical solution of differential equations. Unlike KT, our estimate is equal to the rate of flux catalyzed by the alpha-ketoglutarate dehydrogenase complex (vTCA), not merely correlated with it. We also estimate the rate of flux catalyzed by aspartate aminotransferase (vTA) and by NADP(+)-dependent malic enzyme (an anaplerotic reaction). The formula for vTCA during administration of [2-13C]acetate is as follows: vTCA = M[(C-2ssLC-4)/[C-4ss(LC-4-LC-2)]], where C-2ss and C-4ss represent steady-state fractional enrichment, LC-2 and LC-4 represent dominant rate constants of C-2 and C-4 of glutamate, respectively, and M is the sum of concentrations of aspartate, glutamate, and intermediates of the CAC. The assumptions underlying our formula are as follows: 1) metabolic steady state is maintained, 2) exchange of molecules between cytosolic and mitochondrial compartments is rapid, 3) 13C enters pools of the CAC only from acetyl CoA via citrate synthase, 4) [citrate]/[glutamate] < 1 + (vTCA/vTA), and 5) (m-[glutamate])/M < C-2ss/C-4ss.
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PMID:Estimation of TCA cycle flux, aminotransferase flux, and anaplerosis in heart: validation with syntactic model. 790 Jul 86

In islets from adult rats injected with streptozotocin during the neonatal period, both a nonmetabolized analog of L-leucine and 3-phenylpyruvate augmented 14CO2 output from islets either prelabeled with L-[U-14C]glutamine or exposed to D-[2-14C]glucose and D-[6-14C]glucose, in a manner qualitatively comparable to that found in islets from control rats. The islets of diabetic rats differed, however, from those of control rats by their unresponsiveness to both the L-leucine analog and a high concentration of D-glucose in terms of increasing 3HOH generation from [2-3H]glycerol, an impaired sparing action of the hexose upon 14CO2 output from islets prelabeled with [U-14C]palmitate, and, most importantly, by a decreased rate of D-[2-14C]glucose and D-[6-14C]glucose oxidation when either incubated at a high concentration of the hexose (16.7 mM) or stimulated by nonglucidic nutrient secretagogues at a low concentration of D-glucose (2.8 mM). In islet homogenates, the activity of glyceraldehyde phosphate dehydrogenase, glutamate decarboxylase, and NADP-malate dehydrogenase was lower in diabetic than control islets. Such was not the case for glutamate-alanine transaminase, glutamate-aspartate transaminase, or glutamate dehydrogenase. The neonatal injection of streptozotocin thus affected, in the adult rats, the activity of several islet enzymes. Nevertheless, the metabolic data suggest that an impaired circulation in the glycerol phosphate shuttle, as observed in response to stimulation of the islets by either a high concentration of D-glucose or nonglucidic nutrient secretagogues, represents an essential determinant of the preferential impairment of glucose-induced insulin release in this model of non-insulin-dependent diabetes.
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PMID:Metabolic response to nonglucidic nutrient secretagogues and enzymatic activities in pancreatic islets of adult rats after neonatal streptozotocin administration. 848 60

The physiological features of the mildiomycin production by Streptoverticillium rimofaciens were examined in iron-sufficient and -deficient media. Activities of NADP-linked glutamate dehydrogenase (GDH) and aspartate aminotransferase (AAT) were markedly enhanced by the addition of 10 micrograms/ml of ferrous ion into culture. Ammonium nitrogen assimilation increased with the increase in mildiomycin production. These indicate that ferrous ion contributes the supply of amino acids as a precursor of mildiomycin production. In the iron-sufficient medium, glutamate, aspartate, serine and arginine in cells were 2 to 10-fold to those in the iron-deficient medium. The major amino acid excreted from cells was arginine in the iron-sufficient culture, while in the iron-deficient culture, valine. Change in the amino acid profile by addition of ferrous ion was useful for mildiomycin biosynthesis, in which ferrous ion played a leading role in amino acid metabolism.
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PMID:Effect of ferrous ion on amino acid metabolism in mildiomycin production by Streptoverticillium rimofaciens. 912 91

The physiological features of the mildiomycin production by Streptoverticillium rimofaciens were examined in iron-sufficient and -deficient media. Activities of NADP-linked glutamate dehydrogenase (GDH) and aspartate aminotransferase (AAT) were markedly enhanced by the addition of 10 micrograms/ml of ferrous ion into culture. Ammonium nitrogen assimilation increased with the increase in mildiomycin production. These indicate that ferrous ion contributes the supply of amino acids as a precursor of mildiomycin production. In the iron-sufficient medium, glutamate, aspartate, serine and arginine in cells were 2 to 10-fold to those in the iron-deficient medium. The major amino acid excreted from cells was arginine in the iron-sufficient culture, while in the iron-deficient culture, valine. Change in the amino acid profile by addition of ferrous ion was useful for mildiomycin biosynthesis, in which ferrous ion played a leading role in amino acid metabolism.
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PMID:Effect of ferrous ion on amino acid metabolism in mildiomycin production by Streptoverticillium rimofaciens 943 91

Two alpha-amylase-producing strains of Aspergillus oryzae, a wild-type strain and a recombinant containing additional copies of the alpha-amylase gene, were characterized with respect to enzyme activities, localization of enzymes to the mitochondria or cytosol, macromolecular composition, and metabolic fluxes through the central metabolism during glucose-limited chemostat cultivations. Citrate synthase and isocitrate dehydrogenase (NAD) activities were found only in the mitochondria, glucose-6-phosphate dehydrogenase and glutamate dehydrogenase (NADP) activities were found only in the cytosol, and isocitrate dehydrogenase (NADP), glutamate oxaloacetate transaminase, malate dehydrogenase, and glutamate dehydrogenase (NAD) activities were found in both the mitochondria and the cytosol. The measured biomass components and ash could account for 95% (wt/wt) of the biomass. The protein and RNA contents increased linearly with increasing specific growth rate, but the carbohydrate and chitin contents decreased. A metabolic model consisting of 69 fluxes and 59 intracellular metabolites was used to calculate the metabolic fluxes through the central metabolism at several specific growth rates, with ammonia or nitrate as the nitrogen source. The flux through the pentose phosphate pathway increased with increasing specific growth rate. The fluxes through the pentose phosphate pathway were 15 to 26% higher for the recombinant strain than for the wild-type strain.
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PMID:Identification of enzymes and quantification of metabolic fluxes in the wild type and in a recombinant aspergillus oryzae strain 987 53

The effect of various metabolic inhibitors on the rate of oxygen consumption by procyclic culture forms of Trypanosoma congolense utilizing proline as substrate was investigated. Cyanide inhibited the rate of oxygen consumption by 81.0 +/- 6.7%, malonate inhibited the rate by 51.6 +/- 1.6% and Antimycin A by 73.1 +/- 5.9%. A combination of cyanide and malonate inhibited the rate of oxygen consumption by 84.9 +/- 6.7% while a combination of antimycin A and malonate inhibited the rate by 81.6 +/- 7.6%. Rotenone had no effect on the rate of respiration except when the intact cells were first permeabilized by digitonin after which rotenone decreased the rate of respiration by 20-30%. Salicylhydroxamate (SHAM) did not have any effect on the rate of oxygen consumption. Enzymes involved in the catabolism of proline with high activities were: proline dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, fumarase, NADP-linked malic enzyme, alanine aminotransferase and malate dehydrogenase. Activities of 1-pyrroline-5 carboxylate dehydrogenase, glutamate dehydrogenase, aspartate aminotransferase and NAD-linked malic enzyme were detectable but lower. The end products of proline catabolism were alanine and glutamate. Unlike the case in Trypanosoma brucei brucei aspartate was not detected. Possible pathways of proline catabolism in procyclic culture forms of T. congolense and of electron transfer are proposed.
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PMID:Catabolism of proline by procyclic culture forms of Trypanosoma congolense. 1042 13

Activities of several metabolic enzymes show distinct patterns of zonation along the intestinal tract of tilapia (Oreochromis niloticus), rainbow trout (Oncorhynchus mykiss) and copper rockfish (Sebastes caurinus). Zonation is species and enzyme specific, with different metabolic activities concentrated in specific areas, and few generalizations can be made. The rockfish show the smallest degree of zonation, with highest activities in the third quarter of the intestine, and shallow gradients to either side, and a general upswing in activity towards the distal end. In the trout, mitochondrial enzyme activities (citrate synthase, glutamate dehydrogenase, malate dehydrogenase) are highest in the pyloric caeca and decrease along the length of the small intestine. This pattern is accentuated for malic enzyme and glucose 6-phosphate dehydrogenase. These enzymes drop precipitously in activity after the first few sections of the small intestine, while other NADP-linked dehydrogenases (isocitrate dehydrogenase, and 6-phosphogluconate dehydrogenase) show moderate activity in pyloric caeca and peak toward the distal section of the small intestine. In tilapia, glutamate dehydrogenase shows a similar decrease as in trout, but citrate synthase peaks towards the distal sections. NADP-dependent dehydrogenases reveal distinct patterns, peaking in different sections of the intestine-malic enzyme in the proximal midsection, glucose 6-phosphate dehydrogenase in the distal mid-section, and isocitrate dehydrogenase in the anal section. Enzyme activities in the stomach of trout and tilapia also show zonation, with the midsection generally displaying the highest activities. A 5-day treatment of tilapia with an intraperitoneal cortisol deposit (25 mg kg(-1) wet mass) drastically alters metabolic performance along the gut in enzyme specific patterns, generally increasing enzyme activities in site-specific arrangements. Cortisol treatment also leads to the expected increases in activities of phosphoenolpyruvate carboxykinase, pyruvate kinase and aspartate aminotransferase in liver, but not in kidney. Aspartate aminotransferase is the only enzyme in brain significantly increased by cortisol treatment. Short-term food deprivation changes enzyme patterns, often resembling those observed after cortisol administration. We conclude that brain, liver and intestinal amino acid metabolism is an important target for cortisol action in fish and that metabolic zonation is a key factor to be reckoned with when analyzing physiological phenomena in the fish intestine.
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PMID:Metabolic zonation in teleost gastrointestinal tract. Effects of fasting and cortisol in tilapia. 1278 63

A comparative assay of nitrogen metabolism enzymes in the Yarrowia lipolytica mutant N1 grown under conditions promoting the overproduction of either alpha-ketoglutaric acid (KGA) or citric acid showed that the overproduction of KGA correlates with an increase in the activities of the NAD- and NADP-linked glutamate dehydrogenase, glutamic-pyruvic transaminase, and glutamic-oxaloacetic transaminase reactions. These reactions are likely to be responsible for the overproduction of KGA by this mutant. In contrast, the overproduction of citric acid correlated with a decline in the activities of the NAD- and NADP-linked glutamate dehydrogenases and with an increase in the activities of glutamine synthetase and glutamate synthase.
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PMID:[Biochemical characterization of the yeast Yarrowia lipolytica overproducing carboxylic acids from ethanol. Nitrogen metabolism enzymes]. 1452 35

Few studies demonstrate at a biochemical level the metabolic profile of both cumulus cells and the oocyte during maturation. The aim of the present study was to investigate the differential participation of enzymatic activity in cumulus cells and in the oocyte during in vitro maturation (IVM) by studying the activity of enzymes involved in the control of amino acid metabolism, alanine aminotransferase (ALT) and aspartate aminotransferase (AST); and the tricarboxylic acid (TCA) cycle, isocitrate dehydrogenase (IDH) and malate dehydrogenase (MDH). No NAD-dependent isocitrate dehydrogenase (NAD-IDH) activity was recorded in cumulus-oocyte complexes (COCs). ALT, AST, NADP-dependent isocitrate dehydrogenase (NADP-IDH) and MDH enzymatic units remained constant in cumulus cells and oocytes during IVM. Specific activities increased in oocytes and decreased in cumulus cells as a result of IVM (P<0.05). Similar activity of both transaminases was detected in cumulus cells, unlike in the oocyte, in which activity of AST was 4.4 times greater than that of ALT (P<0.05). High NADP-IDH and MDH activity was detected in the oocyte. Addition of alanine, aspartate, isocitrate + NADP, oxaloacetate or malate + NAD to maturation media increased the percentage of denuded oocytes reaching maturation (P<0.05), in contrast to COCs in which differences were not observed by addition of these substrates and co-enzymes. The activity of studied enzymes and the use of oxidative substrates denotes a major participation of transaminations and the TCA cycle in the process of gamete maturation. The oocyte thus seems versatile in the use of several oxidative substrates depending on the redox state.
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PMID:Involvement of enzymes of amino acid metabolism and tricarboxylic acid cycle in bovine oocyte maturation in vitro. 1474 94


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