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)

We present a diagnostic and therapeutic protocol designed to prevent clinical expression of inborn errors of urea synthesis in the neonatal period, and discuss the long-term developmental outcome of survivors. The families of 32 infants, among 43 identified prenatally as being at risk for a urea cycle disorder, chose to have their infants treated according to a diagnostic and therapeutic protocol, beginning at birth. The therapy was effective in avoiding neonatal hyperammonemic coma and death in seven patients with carbamoyl phosphate synthetase deficiency, argininosuccinate synthetase deficiency, and argininosuccinate lyase deficiency. When treated prospectively, five of eight patients with ornithine transcarbamylase deficiency avoided severe hyperammonemia and survived the neonatal period. Two patients with carbamoyl phosphate synthetase deficiency and two with ornithine transcarbamylase deficiency have subsequently died; three additional patients with the latter disorder have received orthotopic liver transplants. Our experience suggests that these surviving patients have had a more favorable neurologic outcome than patients rescued from neonatal hyperammonemic coma. However, all of them require a burdensome medical regimen and may have handicaps that include impairment of development and recurrent episodes of hyperammonemia. Further, those with deficiency of carbamoyl phosphate synthetase or ornithine transcarbamylase have a high mortality rate.
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PMID:Prospective treatment of urea cycle disorders. 172 Apr 58

Carbamyl phosphate synthetase deficiency (CPSD) is one of the enzyme defects of the urea cycle and inherited as an autosomal recessive. A definitive enzymatic diagnosis of CPSD can be made by biochemical assay of liver biopsy material, but not of cultured fibroblasts. In pregnancy at risk for CPSD, prenatal diagnosis was attempted by fetal liver biopsy, performed at 22 weeks of gestation. CPS activity was present and a healthy baby was delivered at term. The technique employed for fetal liver biopsy is described together with an evaluation of its possible role in prenatal diagnosis.
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PMID:[Prenatal diagnosis of carbamyl phosphate synthetase deficiency by fetal liver biopsy]. 174 57

Twelve patients with peripheral arterial occlusive disease were evaluated prospectively in an effort to further investigate the etiology of pedal and lower leg edema that occurs following revascularization (e.g., aorto-iliac or femoropopliteal bypass). Serum total protein, albumin, blood urea nitrogen, and creatinine levels were measured (in addition to peripheral venous pressure), and lymphoscintigraphy of the lower leg was performed. These parameters were assessed just prior to surgery, four weeks postoperatively, and again at follow-up. The serum levels obtained four weeks after surgery and on subsequent follow-ups were significantly higher than the preoperative values. Preoperative peripheral venous pressure was not significantly different from that obtained after surgery. There was no correlation between these pressure measurements and the degree of edema (Grades I to IV correspond to increasing degrees of severity). For both the supine and upright positions, lymphoscintigraphic counts in the inguinal region were significantly higher after surgery. However, the relative increase was dependent upon the severity of edema. The postoperative lymphoscintigraphic count in the upright position was 77 +/- 33 CPS in patients with Grades I and II edema (n = 6) and 20.6 +/- 16.2 CPS in patients with Grades III and IV edema (n = 10) (p less than 0.01). Thus, a lesser degree of postoperative pedal and lower leg edema was associated with higher lymphoscintigraphic counts. We conclude that major contributors to the development of lower extremity edema following arterial reconstruction are failed capillary hydrostatic pressure and interrupted lymphatic drainage.
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PMID:99mTc-HSA lymphoscintigraphy and leg edema following arterial reconstruction. 175 91

Dehydroepiandrosterone (DHEA), administered per os, serves to prevent or retard the development of a variety of genetic and induced disorders in mice and rats. This treatment also results in the development of hepatomegaly, a change of liver color from pink to mahogany, peroxisome proliferation in hepatocytes and alterations in hepatocyte mitochondria morphology and respiration. We used one- and two-dimensional polyacrylamide gel electrophoresis (PAGE) to identify changes in the relative levels of liver proteins produced by DHEA treatment of rodents. In mouse liver, there were apparent increases in the levels of 26 proteins and decreases in the levels of 7 proteins. Of the induced proteins the most prominent had Mr approximately 72 K; this protein was identified in a previous study as enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase. Another protein of Mr approximately 28 K, of unknown nature, also was induced markedly by DHEA treatment of mice and rats. A protein of Mr approximately 160 K, which was identified as carbamoyl phosphate synthetase-I (CPS-I), was decreased markedly by DHEA action. This enzyme, which comprises approx. 15-20% of mitochondrial matrix protein, is involved in the entry and rate-limiting step of the urea cycle. The specific activity of CPS-I also was significantly decreased by DHEA, but serum urea levels were normal. To determine whether steroids other than DHEA also induced similar changes, mice were treated with various steroids for 14 days and, thereafter, liver proteins were evaluated by SDS-PAGE: estradiol-17 beta and isoandrosterone induced both the approximately 72 and approximately 28 kDa proteins, testosterone and androsterone induced the 28 kDa protein only, but etiocholanolone, pregnenolone and progesterone were without effect. The findings of this study serve to demonstrate that: (i) hepatic protein levels are affected by DHEA treatment of mice and rats; (ii) liver CPS-I activity is decreased significantly by DHEA treatment, but serum urea levels remain within the normal range; and (iii) sex steroids and some of their precursors, when administered per os, also alter liver protein levels.
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PMID:Inhibition of carbamoyl phosphate synthetase-I by dietary dehydroepiandrosterone. 182 77

A selective interaction of rat liver carbamoyl phosphate synthetase I with cardiolipin, and other anionic phospholipids, has been demonstrated. The enzymatic activity of the synthetase is inhibited by cardiolipin and, to a lesser extent, by phosphatidylglycerol, phosphatidylinositol, and phosphatidylserine. This group of anionic phospholipids also induced a conformational change in the synthetase, yielding a species with increased exposure of the linkages between independently folded domains of the enzyme, as determined by limited proteolysis under nondenaturing conditions. The interaction of cardiolipin with carbamoyl phosphate synthetase I was a fairly slow process, with complex kinetics, and was apparently irreversible. The inclusion of Mg2+ or of MgATP in the incubation mixture prevented the cardiolipin effects. The zwitterionic phospholipids phosphatidylcholine and phosphatidylethanolamine had negligible effects on the structure and activity of the synthetase. This interaction between cardiolipin and carbamoyl phosphate synthetase I potentially constitutes one of the mechanisms by which the synthetase forms its loose association with the inner mitochondrial membrane. Multiple mechanisms, including synthetase conformational changes, cardiolipin phase changes, and ATP/ADP binding site involvement, are possibly involved in the phospholipid/synthetase interaction and the resulting potential regulatory mechanism(s) for urea cycle activity.
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PMID:The interaction of cardiolipin with rat liver carbamoyl phosphate synthetase I. 189 84

Perfusion of rat liver had led to the suggestion that oxygen tension, rather than the distribution of enzymes of urea synthesis, plays a key role in the regulation of urea synthesis in the periportal and pericentral areas of the liver lobule [F. W. Kari, H. Yoshihara and R. G. Thurman (1987) Eur. J. Biochem. 163, 1-7]. We have directly tested the effect of oxygen concentration on ureogenesis under steady-state conditions in isolated hepatocytes perifused with physiological concentrations of ammonia. We found that ureogenesis is independent of the oxygen concentration. Only at oxygen concentrations below 25 microM (which is below the oxygen concentration in liver) was urea synthesis decreased. This was because insufficient production of ATP led to decreased flux through carbamoyl-phosphate synthase. It is concluded that oxygen does not control urea synthesis.
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PMID:Oxygen tension does not affect urea synthesis in perifused rat hepatocytes. 199 25

Carbamoyl phosphate synthetase I, the most abundant protein of rat liver mitochondria, plays a key role in synthesis of urea. Because aging affects some liver functions, and because there is no information on the levels of carbamoyl phosphate synthetase I during aging, we assayed the activity of this enzyme and determined immunologically the level of carbamoyl phosphate synthetase I in liver homogenates from young (4 months) and old (18 or 26 months) rats. In addition, we used electron microscopic immunogold procedures to locate and measure the amount of the enzyme in the mitochondrial matrix. There is no significant change in enzyme activity or enzyme protein content with age, although there is a higher concentration of the enzyme in the mitochondria (c. 1.5 times greater) from old rats, which is compensated by a decrease in the fractional volume of the mitochondrial compartment during aging.
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PMID:Levels of carbamoyl phosphate synthetase I in livers of young and old rats assessed by activity and immunoassays and by electron microscopic immunogold procedures. 230 2

1. Amino acid metabolism was studied in control virgin rats, lactating rats and virgin rats protein-pair-fed with the lactating rats (high-protein virgin rats). 2. Urinary excretion of nitrogen and urea was higher in lactating than in control virgin rats, and in high-protein virgin rats it was higher than in lactating rats. 3. The activities of urea-cycle enzymes (units/g) were higher in high-protein virgin than in lactating rats, except for arginase. In lactating rats the activities of carbamoyl-phosphate synthase, ornithine carbamoyltransferase and argininosuccinate synthase were lower than in control virgin rats. When the liver size is considered, the activities in lactating rats were similar to those in high-protein virgin rats, except for arginase. 4. N-Acetylglutamate content was higher in high-protein virgin rats than in the other two groups. 5. The rate of urea synthesis from precursors by isolated hepatocytes was higher in high-protein virgin rats than in the other two groups. 6. The flooding-dose method (L-[4-3H]phenylalanine) for measuring protein synthesis was used. The absolute synthesis rates of mammary gland, liver and small-intestinal mucosa were higher in lactating rats than in the other two groups, and in high-protein virgin rats than in control virgin rats 7. These results show that the increased needs for amino acids during lactation are met by hyperphagia and by a nitrogen-sparing mechanism.
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PMID:Amino acid metabolism and protein synthesis in lactating rats fed on a liquid diet. 239 94

The infusion of ether anesthaetized rats with 0.2 M (1 mmols in total) ammonium acetate or glutamine were compared with the infusion of 0.2 M NaCl. The levels of circulating glucose, amino acids, lactate, urea and ammonium were measured as well as liver glycogen and tissue amino acids and the liver and muscle activities of carbamoyl phosphate synthetases I and II, glutamate dehydrogenase, glutamine synthetase and adenylate deaminase. Neither treatment altered the glucose and glycogen homeostasis. The infusion of ammonium did not result in increases in circulating ammonium, but resulted in increased circulating urea after a short delay; the infusion of glutamine resulted also in urea production but much later on. Glutamine infusion also resulted in increased tissue free amino-acid levels. There was little alteration in enzyme activities, except for decreased glutamine synthetase and adenylate deaminase activity in muscle of glutamine-infused rats and higher tissue carbamoyl phosphate synthetase II. The results agree with a fast removal of infused ammonium, and maintenance of glutamine, with their channeling towards urea production at a rate comparable with that of infusion, that did not alter significantly the homeostasis of the experimental animals.
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PMID:Glutamine and ammonium handling by anaesthetized rats. 247 81

ICR female mice infected with cercariae of Schistosoma mansoni exhibited a significant decrease in both total and specific activities of carbamoyl-phosphate synthetase (ammonia) (EC 6.3.4.16) and ornithine carbamoyltransferase (EC 2.1.3.3), and also in the serum urea level. Intraperitoneal administration of the S. mansoni egg granulomas or 15,000g X 30 min supernatant fluid of their extract into the uninfected, normal mice also significantly decreased the total and specific activities of both enzymes without any appreciable histopathological influence on their livers. S. mansoni viable eggs caused a significant decrease in the total and specific activities of carbamoyl phosphate synthetase (ammonia) alone as well as active intraperitoneal inflammation when inoculated into the normal mice by the same route. There was no difference in the amount of food intake between the control and these experimental mice. These findings suggest that the granuloma or inflammatory cells induced by schistosome eggs produce some factor(s) which may be responsible for reduction of these enzymatic activities in experimental schistosomiasis mansoni.
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PMID:Schistosoma mansoni: suppression of carbamoyl phosphate synthetase (ammonia) and ornithine carbamoyltransferase activities in the liver of infected mice. 249 16


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