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)

The promoter of the gene (CPS) encoding rat carbamyl phosphate synthetase I has been mapped 5' to a segment of about 525 nucleotides upstream from the transcription start point and, when analyzed in liver nuclear extracts, contained six well-defined protein-recognition elements, designated CPS sites I-VI. All six elements were recognized, with varying affinities, by CAAT and enhancer-binding protein (C/EBP alpha) produced in bacteria. Oligodeoxyribonucleotides corresponding to CPS site II or to the C/EBP alpha-recognition element of the ALB promoter, site D, competed with the six CPS-promoter elements in footprinting assays. However, mutagenesis of the C/EBP alpha-recognition element, 5'-GTTGCAAC, at the core of site II was sufficient to abolish transactivation of the CPS promoter by C/EBP alpha in co-transfected HepG2 cells. These findings indicate that the CPS promoter contains multiple recognition elements for factors with DNA-binding specificities similar to C/EBP proteins. Activation by C/EBP alpha, however, requires promoter site II.
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PMID:The carbamyl phosphate synthetase promoter contains multiple binding sites for C/EBP-related proteins. 151 97

On the basis of homology, the mammalian CAD (glutamine-dependent carbamyl phosphate synthetase-aspartate transcarbamylase-dihydroorotase) gene appears to have arisen from the fusion of four separate ancestral genes. Evidence for two of these precursor genes is found in the carbamyl phosphate synthetase (CPSase) domain of CAD. In prokaryotes, such as Escherichia coli CPSase is encoded by two distinct cistrons of the carAB operon. Whereas carA and carB are separated by a short noncoding intercistronic region, the homologous sequences of the CAD gene encode an amino acid bridge. This bridge connects the subdomains of the CAD CPSase. We constructed a bacterial carAB fusion gene in which the intercistronic region codes for a hamster bridgelike sequence. The fused carAB gene directs the synthesis of a stable bifunctional polypeptide whose glutamine-dependent CPSase activity is comparable to the E. coli CPSase holoenzyme. The fusion in E. coli of the single gene counterparts of CAD demonstrates a potential model system to study the genetic events that lead to gene fusion and the creation of multienzymatic proteins.
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PMID:Evidence that mammalian glutamine-dependent carbamyl phosphate synthetase arose through gene fusion. 151 89

Acetylglutamate and ATP accelerate the oxidative inactivation of carbamoyl phosphate synthetase I by mixtures of Fe3+, ascorbate, and O2, but the mechanism of the inactivation differs with each ligand. In the presence of acetylglutamate, MgATP prevents, Mg2+, Mn2+, and catalase have no effect, and EDTA increases the inactivation, and the two phosphorylation steps of the enzyme reaction are lost simultaneously. The inactivation appears to be mediated by dehydroascorbate and is associated with the reversible oxidation of the highly reactive cysteines 1327 and 1337 and with oxidation of non-thiolic groups in the second 40-kDa domain (the enzyme consists of 4 domains of 40, 40, 60, and 20 kDa, from the amino terminus). The data are consistent with oxidation of groups at or near the site for ATPA (ATPA yields Pi; ATPB yields carbamoyl phosphate), and with the location of this site at the interphase between the second 40-kDa and the COOH-terminal domains. The oxidative inactivation promoted by ATP is inhibited by Mg2+, Mn2+, catalase, and EDTA, is not mediated by dehydroascorbate, and is not associated with oxidation of cysteines 1327 and 1337. Groups in the 60-kDa domain are oxidized. The phosphorylation step involving ATPB is lost preferentially, and the inactivation and the binding of ATPB exhibit the same dependency on the concentration of ATP. The results indicate that the oxidation is catalyzed by FeATP bound at the site for ATPB and support the binding of ATPB in the 60-kDa domain. We also demonstrate that mercaptoethanol, reducing impurities in glycerol, and dithioerythritol, in the presence of EDTA, replace ascorbate in the oxidative system. In addition, we study the influence of the oxidation on the degradation of the enzyme by rat liver lysosomes, mitochondria, and cytosol.
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PMID:Oxidative inactivation of carbamoyl phosphate synthetase (ammonia). Mechanism and sites of oxidation, degradation of the oxidized enzyme, and inactivation by glycerol, EDTA, and thiol protecting agents. 153 38

Previous studies using intact rat liver mitochondria have shown that the soluble matrix enzymes carbamoyl-phosphate synthase (ammonia) (CPS) and ornithine carbamoyltransferase (OCT) display some kinetic properties which would not be observed if they were homogeneously distributed in the matrix. In the present work we have extended these studies, using toluene-treated mitochondria which are fully permeable to substrates and inhibitors, yet retain 90% of their soluble enzymes. The results provide evidence of functional organization of CPS and OCT in situ. The major findings are as follows. (1) The apparent Km values of matrix OCT for carbamoyl phosphate and ornithine are respectively 8 and 2 times those measured for the soluble enzyme. delta-N-Phosphonacetyl-L-ornithine inhibits OCT in situ less than in solution, especially when carbamoyl phosphate is synthesized in the mitochondria rather than added to the medium. (2) During citrulline synthesis from endogenously generated carbamoyl phosphate, the concentration of the latter in permeabilized mitochondria is more than 10 times that in the medium, although the mitochondria are freely permeable to added molecules of this size. (3) Endogenously formed carbamoyl phosphate is used preferentially by OCT in situ; addition of a 200-fold excess of unlabelled carbamoyl phosphate has little effect on the conversion of labelled endogenously formed carbamoyl phosphate into citrulline by matrix OCT. (4) The synthesis de novo of carbamoyl phosphate from NH3, HCO3- and ATPMg is the same in the presence and absence of ornithine. (5) Studies with co-immobilized CPS and OCT gave results concordant with some of the above observations and with previous ones with intact mitochondria.
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PMID:Kinetic properties of carbamoyl-phosphate synthase (ammonia) and ornithine carbamoyltransferase in permeabilized mitochondria. 154 Jan 32

Previous studies in our laboratories have revealed that juvenile visceral steatosis mice show suppressed transcription of urea cycle enzyme genes during development and are systemically deficient in carnitine. It has not yet been explained, however, how this carnitine deficiency relates to the abnormal gene expression. We investigated the effect of carnitine on abnormal gene expression, growth retardation, and fatty liver. Carnitine administration relieved the suppression of the developmental induction of two urea cycle enzymes examined, carbamoyl-phosphate synthetase and argininosuccinate synthase, and kept the activities of enzymes normal. However, carnitine did not reduce accumulated lipid in the liver to the normal level. These results suggest that carnitine deficiency plays an important role in the abnormal expression of urea cycle enzyme genes and that the abnormal expression of the genes is not directly caused by lipid accumulation in the liver.
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PMID:Carnitine administration to juvenile visceral steatosis mice corrects the suppressed expression of urea cycle enzymes by normalizing their transcription. 154 87

This paper examines the relative impact of demographic characteristics of the child, family structure, and economic variables on types of child abuse and neglect. The current analysis is based on data from the second National Incidence Study of Child Abuse and Neglect (NIS-2), which collected information from both CPS and non-CPS agencies (e.g., schools, hospitals) in a national sample of 29 counties (Westat, 1988). The NIS-2 offers a unique opportunity to examine abuse and neglect issues with a large, national data set. This paper looks at a series of exploratory logistic regression models to distinguish between four different types of maltreatment: (a) physical abuse, (b) sexual abuse, (c) emotional maltreatment, and (d) physical neglect. Our findings show that physical neglect, in comparison with the other types of abuse, is the most predictable and distinguishable. It is most clearly related to economic factors such as low income and Aid to Families with Dependent Children (AFDC) status, regardless of race. Additionally, both sexual abuse and physical neglect occur at younger ages than previously shown. The policy implications for these findings are discussed.
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PMID:The links between types of maltreatment and demographic characteristics of children. 819 12

Coronary vasoreactivity of patients with chest pain syndrome (CPS, 18 patients) was examined with intracoronary acetylcholine infusion test (ACh). For comparison, 10 patients with vasospastic angina (VSA) and 17 patients without chest pain (control group) were used. The luminal diameters of coronary arteries were measured before and after ACh, and the maximal value of constriction rate of each segment (MCR) was used as index of vasoreactivity in each patient. By the ACh test, an average MCR of 42 +/- 23% was observed in CPS, 84 +/- 17% in VSA, and 26 +/- 12% in the control group. In CPS, chest pain was induced by ACh in 7 patients (group I), but was not induced in the other 11 patients (group II). The average MCR of group I (66 +/- 18%) was significantly higher than group II (28 +/- 9%, p less than 0.01) and the control group (p less than 0.01), though lower than VSA (p less than 0.05). These findings suggest that increased coronary vasoreactivity may play an important role in the chest pain development in CPS.
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PMID:Coronary artery vasoreactivity to intracoronary acetylcholine infusion test in patients with chest pain syndrome. 156 38

This study was conducted to examine the relationship between prenatal exposure to drugs and parenting stress and child maltreatment. The sample was comprised of 48 subjects including 24 drug-exposed children and a comparison group of 24 non-drug-exposed children matched on age, race, gender and socioeconomic status. The subjects' age ranged from 1 to 33 months with a mean of 13 months. As predicted, mothers who used drugs during pregnancy reported higher levels of stress than foster mothers and comparison mothers on total parenting stress, child related stress, and parent related stress as measured by the Parenting Stress Index (Abidin, 1990). Biological mothers and foster mothers of drug-exposed infants scored higher than comparisons on child-related stress, most notably in the areas of hyperactivity, distractability and adaptability. A strong association was found between maternal use of drugs and child maltreatment serious enough to necessitate removal of the children by CPS. Over 40% of the drug-exposed children were in foster care, most often with maternal grandmothers. Most mothers who used drugs during pregnancy were polysubstance abusers and 21% were intravenous drug users increasing the risk of HIV infection for mothers and children. Implications for intervention are discussed.
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PMID:Parenting stress and child maltreatment in drug-exposed children. 161 67

We have isolated and sequenced the genomic DNA from the slime-mould Dictyostelium discoideum multi-gene (PYR1-3) encoding the carbamoyl phosphate synthetase II domain (CPSase, EC.6.3.5.5). We describe sequencing by oligo-walking directly on PCR product in the solid-phase, avoiding subcloning procedures. The 2.4 kb fragment completes the sequence of the PYR1-3 gene, has no introns, and has the same structure as the rudimentary gene of Drosophila melanogaster. Comparison with the carbamoyl phosphate synthetases (CPSase I and CPSase II) of other species supports the hypothesis that this gene has arisen by tandem duplication from a smaller common ancestral gene in the progenote.
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PMID:Carbamoyl phosphate synthetase (CPSase) in the PYR1-3 multigene of Dictyostelium discoideum. 162 25

The CAD multidomain protein, which includes active sites of carbamyl phosphate synthetase II (CPS II, glutamine-dependent), aspartate transcarbamylase, and dihydroorotase, was immunostained in normal rat brains, the gliotic brains of myelin-deficient mutant rats, and brains from normal weanling hamsters. In each of these tissues CAD was observed in cells resembling astrocytes. In hamster brain, CAD immunofluorescence was also found in cells closely related to astrocytes, i.e., the Bergmann glia in cerebellum and the tanycytes surrounding the third ventricle. The astrocytic identity of the CAD-positive cells in rat brain was confirmed by double immunofluorescence staining with antibodies against glial fibrillary acidic protein (GFAP). The two enzymes carbonic anhydrase and glutamine synthetase occur in the cytoplasm of normal astrocytes in gray matter and of reactive astrocytes during gliosis. Products of each enzyme, i.e., bicarbonate and glutamine, are required for the CPS II reaction, which is the first step in the biosynthesis of pyrimidines. Therefore, the present results suggest roles for carbonic anhydrase and glutamine synthetase, as well as CAD, in pyrimidine biosynthesis in brain and a role for the astrocytes in the de novo synthesis of pyrimidines.
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PMID:Localization of the multifunctional protein CAD in astrocytes of rodent brain. 167 39


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