Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.3.5.5 (CPS)
 1,262 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pent-4-enoate at 0.1 to 1.0 mM strongly inhibited urea synthesis in isolated rat hepatocytes. Pent-4-enoate at the same concentrations markedly decreased concentrations of N-acetyl-L-glutamate, an essential activator of carbamoyl-phosphate synthase-I (EC 2.7.2.5), and the decrease was well in parallel with the inhibition of urea synthesis by pent-4-enoate. This compound also lowered cellular concentrations of acetyl-CoA, a substrate of acetylglutamate synthase (EC 2.3.1.1). Pent-4-enoate in a dose of 1 mM did not significantly affect cellular concentrations of ATP, and had no direct effect on acetylglutamate synthase activity. These results suggest that the inhibition of urea synthesis by pent-4-enoate is due to decrease in N-acetyl-L-glutamate concentration and that the decrease is probably brought about by decreased rate of its synthesis due to the lowered concentration of cellular acetyl-CoA.
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PMID:Inhibition of urea synthesis by pent-4-enoate associated with decrease in N-acetyl-L-glutamate concentration in isolated rat hepatocytes. 50 1

Increased blood ammonia was induced in fasting mice by ip administration of 200 mg/kg Na-valproate followed 1 h later by 13 and 4 mmol/kg alanine and ornithine, respectively. When valproate was not used blood or liver ammonia was not increased, but increases were observed in liver glutamate (5-fold), glutamine (2-fold), aspartate (5-fold), acetylglutamate (15-fold), citrulline (35-fold), argininosuccinate (11-fold), arginine (11-fold), and urea (3-fold). The level of carbamoyl phosphate (less than 2 nmol/g) was, by far, the lowest of all urea cycle intermediates. The large increase in citrulline indicates that argininosuccinate synthesis was limiting, and that the increase in acetylglutamate induced a considerable activation of carbamoyl phosphate synthetase, which agrees with theoretical expectations, irrespective of the actual KD value for acetylglutamate. Pretreatment with valproate resulted in lower hepatic levels of glutamate, glutamine, aspartate, acetyl-CoA, and acetylglutamate. At the level found of acetylglutamate the activation of carbamoyl phosphate synthetase would be expected to be similar to that without valproate. Indeed, the levels of citrulline were similar with or without valproate. Argininosuccinate, arginine, and urea levels exhibited little if any change. Although the model used may not replicate exactly the situation in patients, from our results it appears that changes in citrullinogenesis or in other steps of the urea cycle do not account for the increase in blood ammonia induced by valproate, and it is proposed that valproate may alter glutamine metabolism.
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PMID:Changes in urea cycle-related metabolites in the mouse after combined administration of valproic acid and an amino acid load. 250 68

Citrulline synthesis, mostly regulated at the carbamoyl-phosphate synthase I (EC 6.3.4.16) step by the intramitochondrial concentration of ATP and/or N-acetylglutamate is tested with four organic acids: propionate, alpha-ketobutyrate, dipropyl-acetate and 4-pentenoate. In the presence of 10 mM succinate, as the oxidizable substrate, citrullinogenesis was only inhibited by propionate and 4-pentenoate. With 10 mM L-glutamate, a significant inhibition was observed with the four acids. After the addition of ATP and N-acetylglutamate to uncoupled mitochondria, no inhibition could be demonstrated with dipropylacetate and 4-pentenoate. However, a slight inhibition remained with propionate and alpha-ketobutyrate. When mitochondria were incubated with 10 mM L-glutamate, ATP decreased with propionate, dipropylacetate and 4-pentenoate. Under the same conditions, N-acetylglutamate synthesis was strongly inhibited by each organic acid. The decrease of N-acetylglutamate synthesis was related to the constant diminution of intramitochondrial acetyl-coenzyme A (CoA) and to the increase of propionyl-CoA with propionate and alpha-ketobutyrate. Acetyl-CoA and propionyl-CoA are respectively substrate and competitive inhibitor of the N-acetylglutamate synthase (EC 2.3.1.1). Each acid displayed its optimum inhibition at concentrations between 1 and 2 mM. At these acid concentrations, mitochondria had the lowest acetyl-CoA content and the highest propionyl-CoA content.
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PMID:Effects of organic acids on the synthesis of citrulline by intact rat liver mitochondria. 287 43

Valproate (0.5-5 mM) strongly inhibited urea synthesis in isolated rat hepatocytes incubated with 10 mM-alanine and 3 mM-ornithine. Valproate at the same concentrations markedly decreased concentrations of N-acetylglutamate, an essential activator of carbamoyl-phosphate synthetase I (EC 6.3.4.16), in parallel with the inhibition of urea synthesis by valproate. This compound also lowered the cellular concentration of acetyl-CoA, a substrate of N-acetylglutamate synthase (EC 2.3.1.1); glutamate, aspartate and citrulline were similarly decreased. Valproate in a dose up to 2 mM did not significantly affect the cellular concentration of ATP and had no direct effect on N-acetylglutamate synthesis, carbamoyl-phosphate synthetase I and ornithine transcarbamoylase (EC 2.1.3.3) activities.
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PMID:Inhibition of ureagenesis by valproate in rat hepatocytes. Role of N-acetylglutamate and acetyl-CoA. 641 45

As a result of recent advances in molecular cloning, protein expression, and X-ray crystallography, it has now become feasible to examine complicated protein structures at high resolution. For those enzymes with multiple catalytic sites, a common theme is beginning to emerge; the existence of molecular tunnels that connect one active site with another. The apparent mechanistic advantages rendered by these molecular conduits include the protection of unstable intermediates and an improvement in catalytic efficiency by blocking the diffusion of intermediates into the bulk solvent. Since the first molecular tunnel within tryptophan synthase was discovered in 1988, tunnels within carbamoyl phosphate synthetase, glutamine phosphoribosylpyrophosphate amidotransferase, asparagine synthetase, glutamate synthase, imidazole glycerol phosphate synthase, glucosamine 6-phosphate synthase, and carbon monoxide dehydrogenase/acetyl-CoA synthase have been identified. The translocation of ammonia, derived from the hydrolysis of glutamine, is the most abundant functional requirement for a protein tunnel identified thus far. Here we describe and summarize our current understanding of molecular tunnels observed in various enzyme systems.
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PMID:Enzymes with molecular tunnels. 1285 15

Since cinnamon has vitamins and minerals in addition to antioxidants compounds in its chemical composition studies have shown the potential of cinnamon supplementation on some important characteristics in the performance of birds. Thus, this study was conducted under the hypothesis that the inclusion of cinnamon in the laying quail diet could influence the performance of the birds through the expression of genes related to antioxidant activity and lipid metabolism. To test this hypothesis, 144 Japanese quail (Coturnix japonica) with an initial age of 18 weeks and average weight of 133g were distributed in a completely randomized design with two treatments: no cinnamon supplementation (NCS-control group) and with supplementation of 9g/kg of cinnamon powder (CPS). The experiment lasted for 84 days. At the end of the experimental period, six animals from each treatment were euthanized by cervical dislocation, blood was collected and organs weighed. Liver tissue was collected for gene expression and biochemical analyses. We observed a significant effect of cinnamon inclusion on the weight of the pancreas (P = 0.0418), intestine (P = 0.0209) and ovary (P = 0.0389). Lower weights of the pancreas and intestine, and a higher ovary weight was observed in birds receiving the CPS diet. Quails fed with cinnamon supplementation also had better feed conversion per egg mass (2.426 g /g, P = 0.0126), and higher triglyceride (1516.60 mg/dL, P = 0.0207), uric acid (7.40 mg/dL, P = 0.0003) and VLDL (300.40 mg/dL, P = 0.0252) contents. A decreased content of thiobarbituric acid reactive substances (TBARS) and lower catalase activity was observed in the liver of quails from the CPS diet (0.086 nmoles/mg PTN, and 2.304 H2O2/min/mg PTN, respectively). Quails from the CPS group presented significantly greater expression of FAS (fatty acid synthase, 36,03 AU), ACC (Acetyl-CoA Carboxylase, 31.33 AU), APOAI (apolipoprotein A-I, 803,9 AU), ESR2 (estrogen receptor 2, 0.73 AU) SOD (superoxide dismutase, 4,933.9 AU) and GPx7 (glutathione peroxidase 7, 9.756 AU) than quails from the control group. These results allow us to suggest that cinnamon powder supplementation in the diet of laying quails can promote balance in the metabolism and better performance through the modulation of antioxidant activity and the expression of genes related to lipid metabolism.
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PMID:The role of cinnamon as a modulator of the expression of genes related to antioxidant activity and lipid metabolism of laying quails. 2926 51