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:6.3.5.5 (CPS)
1,262 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasmodium yoelii infection alters the hepatic levels of key enzymes of urea cycle, viz.carbamoyl phosphates synthetase (EC 6.3.4.16) and ornithine transcarbamoylase (EC 2.1.3.3) and urea levels in mice. The urea level was found elevated in liver, brain and plasma during P. yoelii infection. However, carbamoyl phosphate synthetase and ornithine transcarbamoylase were noticeably decreased during P. yoelii infection. Pyrimethamine treatment (10 mg/kg body weight for 4 days) brought back the altered parameters to normal a week after cessation of drug treatment.
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PMID:Status of urea and related enzymes during Plasmodium yoelii infection and pyrimethamine treatment in mice. 956 49

The sparse fur (spf) mutant mouse, with an X-linked ornithine transcarbamylase deficiency, is a model of congenital hyperammonemia in children. Our earlier studies indicated a deficiency of hepatic carnitine, CoA-SH, acetyl CoA, and ATP in spf mice. We have now studied the effects of a 7-day treatment with acetyl-L-carnitine (ALCAR) in the spf/Y mice on the activity and expression of the respiratory chain enzyme cytochrome c oxidase (COX; EC 1.9.3.1). We found decreased hepatic activity and expression of COX in the untreated hyperammonemic spf/Y mice, which was restored upon ALCAR treatment. Because COX is a mitochondrial membrane protein, we also carried out studies to explain the mechanism of ALCAR through its effect on membrane stability. Our results indicate a decrease of the mitochondrial membrane cholesterol/phospholipid molar ratio (CHOL/PL ratio) with the activity and expression of COX in untreated spf/Y mice. While ALCAR treatment normalized the ratios, it also restored the hepatic ATP production to normal. To study further if there was any effect of ALCAR on the mitochondrial matrix urea cycle enzymes, we measured the activity and expression of mutant ornithine transcarbamylase (OTC; EC 2.1.3.3) and normal carbamyl phosphate synthase-I (CPS-I; EC 6.3.4.16) in spf/Y mice. There was no general effect on the specific activities of the matrix enzymes upon ALCAR treatment, although their mRNA levels were enhanced. Our studies point towards the feasibility of an ALCAR treatment in conjunction with other treatment modalities, e.g. sodium benzoate and/or arginine, to improve the availability of cellular ATP and to counteract the effects of hereditary hyperammonemic syndromes in children.
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PMID:Restoration of hepatic cytochrome c oxidase activity and expression with acetyl-L-carnitine treatment in spf mice with an ornithine transcarbamylase deficiency. 971 4

Citrulline synthesis from glutamine is enhanced remarkably in enterocytes of weanling pigs, but the molecular mechanism(s) involved are not known. The objective of this study was to determine whether a cortisol surge mediates the enhanced expression of intestinal citrulline-synthetic enzymes during weaning. Jejunal enterocytes were prepared from 29-d-old weanling pigs treated with or without metyrapone (an inhibitor of cortisol synthesis), or from age-matched unweaned pigs. The mRNA levels and activities of phosphate-dependent glutaminase (PDG), pyrroline-5-carboxylate synthase (P5CS), ornithine aminotransferase (OAT), carbamoyl-phosphate synthase I (CPS-I) and ornithine carbamoyltransferase (OCT) were determined. The mRNA levels for PDG, P5CS, OAT and OCT were 139, 157, 102 and 55% higher, respectively, in weanling pigs compared with suckling pigs. The activities of PDG and P5CS were 38 and 692% higher, respectively, in weanling pigs compared with unweaned pigs, but the activities of OAT, CPS-I and OCT did not differ between these two groups of pigs. The effects of metyrapone administration to weanling pigs were as follows: 1) prevention of a cortisol surge, 2) abolition of the increases in both mRNA levels and activity of P5CS, 3) no alteration in the mRNA levels and activities of PDG and CPS-I, 4) increases in the mRNA levels for OAT (216%) and OCT (39%) and in OAT activity (30%), and 5) prevention of the increase in intestinal synthesis of citrulline from glutamine. These results suggest that increased P5CS activity reflects in large part the increased levels of P5CS mRNA and is responsible for the increased synthesis of citrulline from glutamine in enterocytes of weanling pigs; these increases may be mediated by a cortisol surge during weaning that can be blocked by metyrapone administration.
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PMID:A cortisol surge mediates the enhanced expression of pig intestinal pyrroline-5-carboxylate synthase during weaning. 1091 30

The mangrove killifish Rivulus marmoratus can tolerate prolonged periods of air-exposure (>1 month). During these periods of emersion, we hypothesized that R. marmoratus would convert potentially toxic ammonia into urea and free amino acids (FAAs). In air-exposed fish, both ammonia (J(Amm)) and urea (J(Urea)) excretion continued at approximately 57 % and 39 %, respectively, of submerged rates. Remarkably, approximately 42 % of the total ammonia excreted during air-exposure was through NH(3) volatilization. Ammonia did not accumulate in whole-body tissues of air-exposed fish, but levels of both urea and some FAAs (primarily alanine and glutamine) were up to twofold higher after 10 days. The activities of the ornithine-urea cycle enzymes carbamoyl phosphate synthetase III and ornithine transcarbamylase increased (by approximately 30 % and 36 %, respectively) in whole-body tissues of air-exposed fish, while levels of arginase remained unchanged. The activities of enzymes involved in amino acid and oxidative metabolism were not significantly different between control and air-exposed fish. Partitioning of the anterior and posterior ends of immersed fish revealed that just over half (57 %) of the total nitrogen (ammonia+urea) was excreted through the anterior end of the fish, presumably via the branchial tissues, while emersed fish increased excretion via the posterior end (kidney+skin). R. marmoratus do not undergo a shift towards ureotelism during air-exposure. Rather, we propose that R. marmoratus are able to survive on land for extended periods without significant ammonia accumulation because they continuously release ammonia, partially by NH(3) volatilization.
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PMID:Nitrogen metabolism and excretion in the mangrove killifish Rivulus marmoratus II. Significant ammonia volatilization in a teleost during air-exposure. 1181 15

Two different approaches provided evidence for a physical interaction between the carbamate kinase-like carbamoyl-phosphate synthetase (CKase) and ornithine carbamoyltransferase (OTCase) from the hyperthermophilic archaeon Pyrococcus furiosus. Affinity electrophoresis indicated that CKase and OTCase associate into a multienzyme cluster. Further evidence for a biologically significant interaction between CKase and OTCase was obtained by co-immunoprecipitation combined with formaldehyde cross-linking experiments. These experiments support the hypothesis that CKase and OTCase form an efficient channeling cluster for carbamoyl phosphate, an extremely thermolabile and potentially toxic metabolic intermediate. Therefore, by physically interacting with each other, CKase and OTCase prevent the thermodenaturation of carbamoyl phosphate in the aqueous cytoplasmic environment.
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PMID:Metabolic channeling of carbamoyl phosphate, a thermolabile intermediate: evidence for physical interaction between carbamate kinase-like carbamoyl-phosphate synthetase and ornithine carbamoyltransferase from the hyperthermophile Pyrococcus furiosus. 1189 35

This study aimed to elucidate the strategies adopted by the African slender lungfish, Protopterus dolloi, to ameliorate the toxicity of ammonia during short (6 days) or long (40 days) periods of aestivation in a layer of dried mucus in open air in the laboratory. Despite decreases in rates of ammonia and urea excretion, the ammonia content in the muscle, liver, brain and gut of P. dolloi remained unchanged after 6 days of aestivation compared with the control fasted for 6 days. For specimens aestivated for 40 days, the ammonia contents in the muscle, liver and gut were significantly lower than those of the control fasted for 40 days, which suggests a decrease in the rate of ammonia production. In addition, there were significant increases in contents of alanine, aspartate and glutamate in the muscle, which suggests decreases in their catabolism. During the first 6 days and the last 34 days of aestivation, the rate of ammonia production was reduced to 26% and 28%, respectively, of the control rate (6.83 micromol day(-1) g(-1) on day 0). During the first 6 days and the next 34 days of aestivation, the averaged urea synthesis rate was 2.39-fold and 3.8-fold, respectively, greater than the value of 0.25 micromol day(-1) g(-1) for the day 0 control kept in water. No induction of activities of the ornithine-urea cycle (OUC) enzymes was observed in specimens aestivated for 6 days, because the suppression of ammonia production led to a light demand on the OUC capacity. For specimens aestivated for 40 days, the activities of carbamoyl phosphate synthetase, ornithine transcarbamylase and argininosuccinate synthetase + lyase were significantly greater than those of the control fasted for 40 days. This is in agreement with the observation that the rate of urea synthesis in the last 34 days was greater than that in the first 6 days of aestivation. P. dolloi aestivated in a thin layer of dried mucus in open air with high O(2) tension throughout the 40 days of aestivation, which could be the reason why it was able to sustain a high rate of urea synthesis despite this being an energy-intensive process. Our results indicate that a reduction in ammonia production and decreases in hepatic arginine and cranial tryptophan contents are important facets of aestivation in P. dolloi.
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PMID:Nitrogen metabolism in the African lungfish (Protopterus dolloi) aestivating in a mucus cocoon on land. 1474 10

The African sharptooth catfish Clarias gariepinus lives in freshwater, is an obligatory air breather, and exhibits high tolerance of environmental ammonia. This study aimed at elucidating the strategies adopted by C. gariepinus to defend against ammonia toxicity during ammonia exposure. No carbamoyl phosphate synthetase (CPS) I or III activities were detected in the liver or muscle of the adult C. gariepinus. In addition, activities of other ornithine-urea cycle (OUC) enzymes, especially ornithine transcarbamylase, were low in the liver, indicating that adult C. gariepinus does not have a "functional" hepatic OUC. After being exposed to 50 or 100 mM NH4Cl for 5 d, there was no induction of hepatic OUC enzymes and no accumulation of urea in tissues of the experimental animals. In addition, the rate of urea excretion remained low and unchanged. Hence, ammonia exposure did not induce ureogenesis or ureotely in C. gariepinus as suggested elsewhere for another obligatory air-breathing catfish of the same genus, Clarias batrachus, from India. Surprisingly, the local C. batrachus did not possess any detectable CPS I or III activities in the liver or muscle as had been reported for the Indian counterpart. There were no changes in levels of alanine in the muscle, liver, and plasma of C. gariepinus exposed to 50 or 100 mM NH4Cl for 5 d; neither were there any changes in the glutamine levels in these tissues. Yet even after being exposed to 100 mM NH4Cl for 5 d, there was no significant increase in the level of ammonia in the muscle, which constitutes the bulk of the specimen. In addition, the level of ammonia accumulated in the plasma was relatively low compared to other tropical air-breathing fishes. More importantly, for all NH4Cl concentrations tested (10, 50, or 100 mM), the plasma ammonia level was maintained relatively constant (2.2-2.4 mM). These results suggest that C. gariepinus was able to excrete endogenous ammonia and infiltrated exogenous ammonia against a very steep ammonia gradient. When exposed to freshwater (pH 7.0) with or without 10 mM NH4Cl, C. gariepinus was able to excrete ammonia continuously to the external medium for at least 72 h. This was achieved while the plasma NH4+ and NH3 concentrations were significantly lower than those of the external medium. Diffusion trapping of NH3 through boundary layer acidification can be eliminated as the pH of the external medium became more alkaline instead. These results represent the first report on a freshwater fish (C. gariepinus) adopting active excretion of ammonia (probably NH4+) as a major strategy to defend against ammonia toxicity when exposed to environmental ammonia.
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PMID:African sharptooth catfish Clarias gariepinus does not detoxify ammonia to urea or amino acids but actively excretes ammonia during exposure to environmental ammonia. 1509 44

The marine gulf toadfish (Opsanus beta) is an unusual teleost fish as it is able to switch between ammoniotelism and ureotelism in response to a variety of laboratory conditions. The present study integrates field work conducted in Biscayne and Florida Bays, USA with laboratory studies to examine ureotelism during the early life history stages of O. beta. Adult toadfish voluntarily nested in artificial shelters placed amongst seagrass beds and were found to be predominantly ureotelic under natural conditions as the internal shelter water had mean urea and ammonia concentrations (N=51) of 14.2+/-1.6 micro mol N l(-1) and 8.9+/-0.9 micro mol N l(-1), respectively. Toadfish successfully spawned in shelters, providing eggs, larvae and juvenile toadfish for laboratory study. In the lab, juvenile toadfish were also ureotelic and urea was excreted in pulsatile events that accounted for 62.0+/-5.9% of total urea-N excreted. Excretion rates of urea-N and ammonia-N were 1.018+/-0.084 micro mol N h(-1) g(-1) and 0.235+/-0.095 micro mol N h(-1) g(-1), respectively. Field-collected eggs, larvae and juveniles expressed significant levels of the ornithine-urea cycle enzymes carbamoyl-phosphate synthetase III, ornithine transcarbamylase and arginase and the accessory enzyme glutamine synthetase, all of which increased in activity as toadfish developed through early life stages. In juveniles, the ammonia 96-h LC(50) value was 875 micro mol N l(-1) and there was a 3-fold increase in ornithine transcarbamylase activity in the 1000 micro mol N l(-1) NH(4)Cl treatment. The results are discussed in the context of the causal factor(s) for ureotelism in toadfish. Furthermore, the results of this study suggest it is unlikely that the adaptive significance of ureotelism in toadfish is a means to prevent fouling nests with ammonia and in turn poisoning offspring; however, additional study is warranted.
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PMID:Dogmas and controversies in the handling of nitrogenous wastes: ureotely and ammonia tolerance in early life stages of the gulf toadfish, Opsanus beta. 1514 35

The primary nitrogen metabolism of the N2-fixing root nodule symbiosis Alnus incana (L.)- Frankia was investigated by 31P and 15N nuclear magnetic resonance (NMR) spectroscopy. Perfusion of root nodules in a pulse-chase approach with 15N- or 14N-labeled NH4+ revealed the presence of the amino acids alanine (Ala), gamma-amino butyric acid, glutamine (Gln), glutamic acid (Glu), citrulline (Cit) and arginine (Arg). Labeling kinetics of the Gln amide-N and alpha-amino acids suggested that the glutamine synthetase (GS; EC 6.3.1.2)-glutamate synthase (GOGAT; EC 1.4.1.13) pathway was active. Inhibition of the GS-catalyzed reaction by methionine sulphoximine abolished incorporation of 15N. Cit was labeled in all three N positions but most rapidly in the omega position, consistent with carbamoyl phosphate as the precursor to which Gln could be the amino donor catalyzed by carbamoyl phosphate synthase (CPS; EC 6.3.5.5). Ala biosynthesis occurred consistent with a flux of N in the sequence Gln-Glu-Ala. 31P NMR spectroscopy in vivo and of extracts revealed several metabolites and was used in connection with the 15N pulse-chase experiment to assess general metabolic status. Stable concentrations of ATP and UDP-glucose during extended perfusions showed that the overall root nodule metabolism appeared undisturbed throughout the experiments. The metabolic pathways suggested by the NMR results were confirmed by high activities of the enzymes GS, NADH-GOGAT and ornithine carbamoyltransferase (OCT; EC 2.1.3.3). We conclude that the primary pathway of NH4+ assimilation in A. incana root nodules occurs through the GS-GOGAT pathway. Biosynthesis of Cit through GS-CPS-OCT is important and is a link between the first amino acid Gln and this final transport and storage form of nitrogen.
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PMID:Primary metabolism in N2-fixing Alnus incana-Frankia symbiotic root nodules studied with 15N and 31P nuclear magnetic resonance spectroscopy. 1517 12

Somatotropin (ST) increases milk production and through coordinated changes in hepatic glucose synthesis and amino acid metabolism in dairy cows. The objective of this study was to determine the effects of ST on hepatic mRNA expression for phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate carboxylase (PC), enzymes that are critical to the synthesis of glucose in liver and hepatic mRNA expression for carbamylphosphate synthetase I (CPS-I), argininosuccinate synthetase (AS), and ornithine transcarbamylase (OTC), critical enzymes of the urea cycle. Eighteen cows were randomly allocated to 2 treatment groups and received either recombinant bovine ST (Posilac; Monsanto, St. Louis, MO) or saline injections at 14-d intervals during a 42-d period. Expression of mRNA was determined using Northern blot analysis. Nuclei, isolated from liver biopsy samples, were used to determine effects of ST on transcription rate of PEPCK. Milk production was increased with ST (37.3 vs. 35.1+/-0.6 kg/ d). Plasma NEFA was increased with ST (299 vs. 156+/-34 microM). There were no differences in the expression of CPS-I, AS, and OTC mRNA with ST. Expression of PEPCK and IGF-I mRNA were increased with ST but PC mRNA was unchanged. The data indicate increased PEPCK mRNA in cows given ST and indicates a greater capacity for gluconeogenesis from gluconeogenic precursors that form oxaloacetate. The effects of ST to elevate PEPCK mRNA expression require chronic administration and involve increased transcription of the PEPCK gene.
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PMID:Bovine somatotropin increases hepatic phosphoenolpyruvate carboxykinase mRNA in lactating dairy cows. 1529 Sep 80


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