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)

During the spontaneous or thyroid hormone (TH)-induced metamorphosis of Rana catesbeiana, developmental changes occur in its liver that are necessary for the transition of this organism from an ammonotelic larva to a ureotelic adult. These changes include the coordinated expression of genes encoding the urea cycle enzymes carbamyl phosphate synthetase (CPS-I) and arnithine transcarbamylase (OTC). Although the expression of these genes is dependent on TH, the mechanisms(s) by which TH initiates this tissue-specific response is thought to be indirect and to involve early TH-induced upregulation of a gene(s), which, in turn, upregulates the coordinated expression of these urea-cycle enzyme genes. Herein, we demonstrate that mRNAs encoding the Rana homologue of the mammalian transcription factor C/EBP alpha (designated RcC/EBP-1) accumulate early in response to TH and that the product of these mRNAs can bind to and transactivate the promoters of both the Rana CPS-1 and OTC genes. These results support the contention that the reprogramming of gene expression in the liver of metamorphosing tadpoles involves a TH-induced cascade of gene activity in which RcC/EBP-1 and, perhaps, other transcription factors coordinate the expression of genes, such as those encoding CPS-I and OTC, whose products are characteristic of the adult liver phenotype.
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PMID:Role for the Rana catesbeiana homologue of C/EBP alpha in the reprogramming of gene expression in the liver of metamorphosing tadpoles. 914 26

The metabolic effects of an ammonium salt on the liver and kidney were investigated. Rats were allowed free access to a 0.28 M ammonium chloride (NH4Cl) solution for 7- and 8-day periods. Serum urea concentration was significantly increased after 8 days of NH4Cl ingestion. However the following hepatic urea cycle enzymes remained unchanged: CPS, OTC, ASS and ASL. The pattern of urinary urea excretion was variable. When the data for the 7-day period were pooled, there was no significant difference between the control and acidotic groups. However, when they were examined on a daily basis, acidosis significantly decreased urea excretion on day 2. Urea excretion then began to increase, reached the control value on day 4 and was significantly greater than the control value on day 7. Urinary ammonium excretion of the acidotic group was significantly increased on day 2 and continued to rise throughout the 7-day period. Renal phosphate-dependent glutaminase of the acidotic group was significantly increased on the eighth day. These data indicate that NH4Cl ingestion alters the pattern of urea excretion in a manner not previously demonstrated.
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PMID:The effect of ammonium chloride on hepatic and renal metabolism in the rat. 919 12

The subcellular localization and biochemical properties of the enzymes of carbamoyl phosphate and urea synthesis were examined in three representatives of fishes of the family Batrachoididae, the gulf toadfish (Opsanus beta), the oyster toadfish (Opsanus tau) and the plainfin midshipman (Porichthys notatus). The primary objective of the study was to compare the biochemical characteristics of these fishes, which represent a range between ammoniotelism and ureotelism (O. beta being facultatively ureotelic), with previous patterns observed for an ammoniotelic teleost (Micropterus salmoides, the largemouth bass) and an obligate ureogenic elasmobranch (Squalus acanthias, the dogfish shark). The present study documents the expression of mitochondrial carbamoyl phosphate synthetase (CPSase) III and cytosolic CPSase II (and its associated enzymes of pyrimidine synthesis, dihydro-orotase and aspartate carbamoyltransferase) in the livers of all three batrachoidid species. Both mitochondrial and cytosolic activities of arginase were present in the livers of all three species, as were cytosolic glutamine synthetase and argininosuccinate synthetase and lyase. However, O. beta also showed mitochondrial glutamine synthetase activity and higher total hepatic levels of glutamine synthetase than either O. tau or P. notatus. Taken together, these observations confirm that the arrangement of these enzymes in the batrachoidid fishes has greater similarity to that of M. salmoides than to that of S. acanthias. However, differences within the family appear to coincide with the different nitrogen excretion strategies. O. tau and P. notatus are primarily ammoniotelic and most closely resemble the ammoniotelic M. salmoides, whereas ureotelism in O. beta is correlated with the presence of a mitochondrial glutamine synthetase and the ability to induce higher total glutamine synthetase activities than O. tau or P. notatus. Additionally, isolated mitochondria from O. beta were able to generate citrulline from glutamine, whereas those from O. tau were not. Also in contrast to S. acanthias, glutamine synthetase activities in the mitochondria of O. beta are consistently lower than those of CPSase III. This and other kinetic observations lend support to the hypothesis that glutamine synthetase may be an important regulatory control point in determining rates of ureogenesis in O. beta.
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PMID:Subcellular localization and biochemical properties of the enzymes of carbamoyl phosphate and urea synthesis in the batrachoidid fishes Opsanus beta, Opsanus tau and Porichthys notatus 931 21

Net portal-drained viscera (PDV) flux of glucose, VFA, ammonia, and urea was determined in pigs fed diets with or without resistant starch. Diets consisted of 65% cornstarch (diet CS), 32.5% cornstarch and 32.5% raw potato starch (diet CPS), or 65% raw potato starch (diet PS); the remaining 35% supplied all amino acids, fat, fiber, minerals, and vitamins. The diets contained twice the maintenance requirement for energy and were fed twice daily to four barrows (initial BW 56 kg) in three periods in a crossover design. The pigs were fitted with catheters in a mesenteric vein, a mesenteric-artery, and the portal vein, and net PDV flux was calculated by multiplying portal-arterial concentration differences and corresponding portal vein flow. Net PDV flux of glucose was significantly less after feeding diets CPS and PS, and portal absorption of ileally digested glucose was 89, 66, and 41% for diets CS, CPS, and PS, respectively. Net PDV flux of VFA was lowest after feeding diet CS and three to four times higher after feeding diets CPS and PS. Net PDV flux of ammonia was highest for diet CS and almost halved after feeding diets CPS and PS. There was a small negative net PDV flux of urea for diets CS and CPS, which significantly increased after feeding diet PS. These results suggest that excretion of nitrogen is shifted from urine to feces primarily by reduction of the net PDV flux of ammonia when resistant starch is fed.
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PMID:Effect of resistant starch on net portal-drained viscera flux of glucose, volatile fatty acids, urea, and ammonia in growing pigs. 933 72

The effect of prolonged metabolic acidosis on hepatic and renal enzymes associated with nitrogen metabolism was investigated. The rates of urinary ammonia and urea excretion were also determined. Administration of 9 mmol HCl daily for 8 days resulted in severe metabolic acidosis. The activity of the first two enzymes of the urea cycle, carbamoyl phosphate synthetase (CPS) and ornithine transcarbamoylase (OTC), was 30% greater in chronically acidotic rats than in pair-fed controls. There was also a fivefold increase in renal phosphate-dependent glutaminase (PDG) activity and an 18 to 24-fold increase in renal ammonia excretion. Urea excretion was not constant in the acidotic group, decreasing during the first 4 days and gradually returning to pair-fed control levels between the fourth and eighth day. The return to control levels of urinary urea excretion coincided with the plateau of urinary ammonia excretion that occurred by day 4 in the acidotic group. A similar pattern of urea nitrogen excretion has been observed in both NH4Cl and HCl acidosis, ie, an initial decrease in urea excretion followed by a gradual increase with time. These results suggest that hepatic urea synthesis does not play a significant role in long-term regulation of the acid-base balance in rats during chronic metabolic acidosis.
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PMID:Alterations in renal and hepatic nitrogen metabolism in rats during HCl ingestion. 947 64

Low levels of all of the enzymes required for urea synthesis via the urea cycle, including mitochondrial glutamine- and acetylglutamate-dependent carbamoyl-phosphate synthetase III (CPSase III) and cytosolic glutamine synthetase, are known to be present in liver of the teleost fish largemouth bass (Micropterus salmoides). The levels of these enzymes are higher than those in most other teleosts, but they are significantly lower than the levels present in liver of ureoosmotic elasmobranchs. The purpose of this study was to assess the physiological role of CPSase III in the context of urea synthesis in adult bass. The results showed that urea-N accounts for about 30% of the total nitrogen (ammonia-N plus urea-N) excreted under control conditions. The rate of urea-N excretion did not increase in response to exposure to 1 mM NH4Cl (3 days) or 0.25 mM NH4Cl (12 days) in the external water, except for a transient increase after a day or two of exposure. CPSase III activity in liver also did not increase in response to exposure to ammonia. Adult largemouth bass, while apparently ureogenic, are primarily ammonotelic and remain so even in the presence of relatively high concentrations of ammonia in the external environment. The total units of CPSase III activity in liver are not sufficient to account for the quantity of urea that is excreted. However, CPSase III and ornithine carbamoyltransferase (OCTase) activities were found to be present in intestinal tissue and, unexpectedly, in muscle tissue. The total units of CPSase III and OCTase in muscle, intestine, and liver appear to be sufficient to account for the observed rate of urea excretion. The sequence of CPSase III cDNA was determined, which permitted the use of ribonuclease protection assays to demonstrate the presence of CPSase III mRNA in these tissues.
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PMID:Nitrogen excretion and expression of carbamoyl-phosphate synthetase III activity and mRNA in extrahepatic tissues of largemouth bass (Micropterus salmoides). 947 89

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

Protein S from Myxococcus xanthus is a member of the beta gamma-crystallin superfamily. Its N and C-terminal domains (NPS and CPS, respectively) show a high degree of structural similarity and possess the capacity to bind two calcium ions per domain. For NPS, their positions were determined by X-ray diffraction at 1.8 A resolution, making use of molecular replacement with the NMR structure as search model. The overall topology of NPS is found to be practically the same as in complete protein S. In natural protein S, the domains fold independently, with a significant increase in stability and cooperativity of folding in the presence of Ca2+. The recombinant isolated domains are stable monomers which do not show any tendency to combine to "nicked" full-length protein S. In order to investigate the stability and folding of natural protein S and its isolated domains, spectroscopic techniques were applied, measuring the reversible urea and temperature-induced unfolding transitions at varying pH. The increment of Ca2+ to the free energy of stabilization amounts to -10 and -5 kJ/mol for NPS and CPS, respectively. For both NPS and CPS, in the absence and in the presence of 3 mM CaCl2, the two-state model is valid. Comparing DeltaGU-->N for CPS (-21 kJ/mol at pH 7, liganded with Ca2+) with its increment in the intact two-domain protein, the stability of the isolated domain turns out to be decreased in a pH-dependent manner. In contrast, the stability of Ca2+-loaded NPS (DeltaGU-->N=-31 kJ/mol, pH 7) is nearly unchanged down to pH 2 where Ca2+ is released (DeltaGU-->N=-26 kJ/mol, pH 2). In intact protein S, the N-terminal domain is destabilized relative to NPS. Evidently, apart from Ca2+ binding, well-defined domain interactions contribute significantly to the overall stability of intact protein S.
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PMID:The domains of protein S from Myxococcus xanthus: structure, stability and interactions. 1006 14

For many years, the urea cycle was considered to be relatively unimportant in the life history of most teleost fishes. In previous studies, we were surprised to find that newly hatched freshwater rainbow trout embryos had relatively high activities of the key urea cycle enzyme, carbamoyl phosphate synthetase III (CPSase III), and other enzymes in the pathway, whereas adult trout had much lower or non-detectable activities. The present study tested the hypothesis that urea cycle enzyme expression is unique to early stages of rainbow trout. In marine Atlantic cod (Gadus morhua) embryos, CPSase III, ornithine transcarbamoylase (OTCase), glutamine synthetase (GSase) and arginase activities were all expressed prior to hatching. Urea excretion was detected shortly after fertilization and rates were high relative to those of ammonia excretion (50-100 % of total nitrogen excreted as urea nitrogen; total=ammonia+urea). Urea concentration was relatively constant in embryos, but ammonia concentration increased by about fourfold during embryogenesis. Two populations of cod embryos were studied (from Newfoundland and New Brunswick), and significant differences in enzyme activities and excretion rates were detected between the two populations. In adult cod, CPSase III was not detectable in liver, white muscle, intestine and kidney tissues, but OTCase, GSase and arginase were present. Adult cod excreted about 17 % of nitrogenous waste as urea. Taken together, these data indicate that early urea cycle enzyme expression is not unique to rainbow trout but is also a feature of Atlantic cod development, and possibly other teleosts. The relatively high urea excretion rates underline the importance of urea as the primary nitrogen excretory product in Atlantic cod during early embryogenesis.
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PMID:Nitrogen excretion and expression of urea cycle enzymes in the atlantic cod (Gadus morhua l.): a comparison of early life stages with adults 1048 24


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