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)

Third-degree burn injury covering 25% of the body surface was imposed on rats. The de novo biosynthesis of purine and pyrimidine nucleotides in the liver of these rats was measured by the incorporation of labeled glycine and bicarbonate into the respective bases. They were increased one day after injury (day 2) and returned to the control values three days after injury (day 4). As expected, the metabolic flow through 5-phosphoribosyl l-pyrophosphate (PPRibP), estimated using [14C]ribose as a tracer, varied in a similar manner. The activities of glutamine phosphoribosylpyrophosphate amidotransferase and carbamoyl-phosphate synthetase II on day 2 did not change significantly. The nucleotide concentrations, effectors of the enzymes, also did not change significantly. The concentrations of PPRibP on days 2 and 4 were 85% higher (P less than .02) and similar to that of controls, respectively, and the elevated concentration was a major factor responsible for the increased nucleotide biosynthesis. Increased synthesis caused the elevation of PPRibP concentrations. There were, however, no significant changes in the factors so far known to regulate PPRibP synthesis.
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PMID:Stimulation of de novo biosynthesis of purine and pyrimidine nucleotides in the liver of rats following burn injury. 246 7

A single injection of the anti-glutamine drug, acivicin (NSC 163501), in tumor-bearing rats in 30 min decreased the activities of amidophosphoribosyltransferase, carbamoyl-phosphate synthetase II and CTP synthetase to 56, 50, and 7% of those of the controls. By 1 hr the activities were down to 32, 13 and 3% and they remained low for 12 hr, after which they slowly returned towards normal range in 72 hr. The decline of the activity of CTP synthetase (a loss of 80% in 10 min) was the most rapid, and the activity only returned to 60% of the controls by 3 days after the acivicin injection. In the hepatoma the concentrations of ATP and UTP changed little, but those of GTP and CTP rapidly decreased, reaching at the lowest point 32 and 2%, respectively, of control values 2 hr after acivicin; concentrations started to rise at 12 hr, reaching normal levels by 48 hr. The drop in enzyme activities preceded the decline in the pools of GTP and CTP. The behavior of enzyme activities and nucleotide concentrations in the host liver had a pattern similar to that in the hepatoma; however, the changes were less extensive than those in the tumor. The differential response between tumor and liver is attributed, in part at least, to the tissue L-glutamine concentration which in the hepatoma (0.5 mM) was 9 times lower than in the liver (4.5mM). The selectivity of acivicin action in inhibiting glutamine-utilizing enzymes is also demonstrated by the lack of effect on aspartate carbamoyltransferase, an enzymic activity which resides in the same complex as that of carbamoyl-phosphate synthetase II. The rapid decline in the activities of glutamine-utilizing enzymes is attributed to an inactivation of the enzymes by acivicin which functions as an active sitedirected affinity analog of L-glutamine. The rapid modulation of the enzymic phenotype and ribonucleotide concentrations by acivicin provides a useful tool for elucidating the role of enzymic and nucleotide imbalance in the commitment of cancer cells to replication and in the targeting of anticancer chemotherapy.
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PMID:Rapid in vivo inactivation by acivicin of CTP synthetase, carbamoyl-phosphate synthetase II, and amidophosphoribosyltransferase in hepatoma. 707 46

The three-dimensional structures of tryptophan synthase, carbamoyl phosphate synthetase, glutamine phosphoribosylpyrophosphate amidotransferase, and asparagine synthetase have revealed the relative locations of multiple active sites within these proteins. In all of these polyfunctional enzymes, a product formed from the catalytic reaction at one active site is a substrate for an enzymatic reaction at a distal active site. Reaction intermediates are translocated from one active site to the next through the participation of an intermolecular tunnel. The tunnel in tryptophan synthase is approximately 25 A in length, whereas the tunnel in carbamoyl phosphate synthetase is nearly 100 A long. Kinetic studies have demonstrated that the individual reactions are coordinated through allosteric coupling of one active site with another. The participation of these molecular tunnels is thought to protect reactive intermediates from coming in contact with the external medium.
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PMID:Channeling of substrates and intermediates in enzyme-catalyzed reactions. 1139 5

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