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)

The pyrimidine metabolism of Giardia lamblia trophozoites (Portland I strain) was studied using whole trophozoites and trophozoite homogenates. Pyrimidines and pyrimidine nucleosides were readily incorporated into nucleic acids. Orotic and aspartic acid incorporations were below the level of detection. Enzymes of the pyrimidine salvage pathway (i.e., thymidine and uridine phosphorylases and thymidine and uridine kinases) were detected in trophozoite homogenates, but the activities of de novo pyrimidine synthesis enzymes (i.e., carbamoyl-phosphate synthase, aspartate transcarbamoylase, dihydroorotase and dihydroorotate dehydrogenase) were below the level of detection in these same homogenates. The evidence presented supports the conclusion that G. lamblia trophozoites appear incapable of synthesizing pyrimidines de novo but are capable of salvaging preformed pyrimidines and pyrimidine nucleosides from the growth medium and the enzymes of this pyrimidine salvage pathway are not organelle associated.
 ...
PMID:Pyrimidine metabolism in Giardia lamblia trophozoites. 709 5

Addition of ammonium ions to isolated rat hepatocytes stimulated the rate of synthesis of pyrimidines. Isolation and quantification of pyrimidine nucleotides orotic acid and the acid-hydrolyzed product of carbamoyl-aspartic acid by ion-exchange chromatography and high-pressure liquid chromatography show a marked stimulation in the incorporation of [14C]bicarbonate in incubations with added ammonium ions. The incorporation into total uridine nucleotides (sigma UMP) was increased twofold in the presence of 5 mM ammonium ion, and approximately eightyfold into orotic acid. There was a parallel increase in labelling of carbamoylaspartic acid from undetectable to a level similar to that of orotic acid. The specific activity of urea formed during the incubations did not change during incubations or in the presence of ammonium ions confirming that the change in labelling of pyrimidine was not due to a change in the specific activity of precursor. Despite the stimulation in incorporation of label into pyrimidines there was no increase in the hepatocyte content of sigma UMP, which was 11.5 mumol/g dry weight, although the orotic acid content increased from 0.09 mumol/g dry weight in the absence of added ammonium ions (but in the presence of 2 mM L-glutamine) to 8.6 mumol/g dry weight with 5 mM ammonium ion. The stimulated incorporation of [14C]bicarbonate in the presence of 5 mM and 10 mM ammonium ion was shown to be due to a stimulated synthesis of carbamoyl phosphate, since greater than 80% of label in the uracil ring was present at position C-2. Incubation of hepatocytes in basal medium (Eagles) containing 2.5% foetal calf serum and 20 mM bicarbonate showed that there was a significant stimulation of pyrimidine synthesis with 1 mM ammonium ion. The stimulatory effect of ammonium ions on incorporation of bicarbonate into pyrimidines was almost completely reversed by 5 mM L-ornithine and was partially reversed by 1 mM L-ornithine. Evidence for a contribution of the urea cycle carbamoyl phosphate synthetase to pyrimidine synthesis is discussed.
 ...
PMID:Effect of ammonium ion on pyrimidine synthesis de novo in isolated rat hepatocytes. 725 Jan 18

The Neurospora crassa arg-2 and the Saccharomyces cerevisiae ortholog CPA1 encode the arginine-specific carbamoyl-phosphate synthetase (CPS-A) small subunit. Arginine decreases synthesis of this subunit through the action of a 5' upstream open reading frame in the mRNA that encodes a cis-regulatory element, the arginine attenuator peptide (AAP), which stalls ribosomes in response to arginine. We performed a comparative analysis of the genomic structure and predicted peptide sequence of the AAP and CPS-A small subunit across many fungi. Differences at the genomic level included variation in intron number and position within the AAP and CPS-A coding regions and differences in known regulatory motifs. Although differences exist in AAP sequence, there were three absolutely conserved amino acid residues in the predicted peptide, including an aspartic acid crucial for arginine-dependent regulation of arg-2 and CPA1. A diverged Basidiomycete AAP was shown to retain function as an Arg-specific negative regulator of translation.
 ...
PMID:Evolutionary changes in the fungal carbamoyl-phosphate synthetase small subunit gene and its associated upstream open reading frame. 1697 58