Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.5 (5'-nucleotidase)
 3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After the administration of cycloheximide (2 mg/kg) the utilization of [2(-14C)]orotic acid for the synthesis of pyrimidine nucleotides of acid-soluble extracts of the liver is not affected for about 7 h. The specific activities of uridine and cytidine components are increased later on, and this increase is higher in the case of cytidine components. Analogous changes undergoes the specific activity of RNA pyrimidine nucleotides. The increased utilization of labeled orotic acid for the synthesis of cytidine nucleotides can be observed also in the kidney and in the small intestine. The enhanced degree of labeling of cytidine nucleotides in vivo cannot be correlated with the activity of cytidine triphosphate synthetase (EC 6.3.4.2) of liver cytosol estimated in vitro. The amination of UTP is suppressed at later intervals after the application of cycloheximide. The same holds true for the activity of uridine phosphorylase (EC 2.4.2.3),5'-nucleotidase (EC 3.1.3.5) ATPase (EC 3.6.1.3) and of liver cytosol. The activity of uridine kinase (EC 2.7.1.48) is increased when tested both with uridine and cytidine as substrates. Cytidine deaminase activity (EC 3.5.4.5) raises markedly 3--5 h after the administration of drug; later on it decreases again.
 ...
PMID:Pyrimidine nucleotide synthesis in rat liver after the administration of cycloheximide. 67 15

Induction studies on pyrimidine metabolizing enzymes in E. coli B have shown that the enzymes fall into three distinct groups according to their induction pattern. a) Cytidine deaminase and uridine phosphorylase, are induced by cytidine, CMP and adenosine; no induction was observed with uridine and AMP; b) thymidine phosphorylase is induced by cytidine, adenosine, all deoxyribonucleosides, CMP, deoxyribonucleotides, deoxyribose and deoxyribose-1-phosphate; c) uridine-cytidine kinase, uracil phosphoribosyltransferase, 5'-nucleotidase, thymidine kinase, are uninducible enzymes. Simultaneous addition of cytidine and glucose partially overcomes the cytidine deaminase and uridine phosphorylase induction. Cytidine deaminase reaches its maximum activity levels, in E. coli growing cells in presence of cytidine, two hours before the uridine phosphorylase activity. Maximum glucose repression of cytidine deaminase and uridine phosphorylase was obtained in correspondence of maximum cytidine induction.
 ...
PMID:Induction of pyrimidine nucleoside metabolizing enzymes in E. coli B. 636 Sep 49

Pyrimidine antagonists, for example, 5-fluorouracil (5-FU), cytarabine (ara-C) and gemcitabine (dFdC), are widely used in chemotherapy regimes for colorectal, breast, head and neck, non-small-cell lung cancer, pancreatic cancer and leukaemias. Extensive metabolism is a prerequisite for conversion of these pyrimidine prodrugs into active compounds. Interindividual variation in the activity of metabolising enzymes can affect the extent of prodrug activation and, as a result, act on the efficacy of chemotherapy treatment. Genetic factors at least partly explain interindividual variation in antitumour efficacy and toxicity of pyrimidine antagonists. In this review, proteins relevant for the efficacy and toxicity of pyrimidine antagonists will be summarised. In addition, the role of germline polymorphisms, tumour-specific somatic mutations and protein expression levels in the metabolic pathways and clinical pharmacology of these drugs are described. Germline polymorphisms of uridine monophosphate kinase (UMPK), orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and methylene tetrahydrofolate reductase (MTHFR) and gene expression levels of OPRT, UMPK, TS, DPD, uridine phosphorylase, uridine kinase, thymidine phosphorylase, thymidine kinase, deoxyuridine triphosphate nucleotide hydrolase are discussed in relation to 5-FU efficacy. Cytidine deaminase (CDD) and 5'-nucleotidase (5NT) gene polymorphisms and CDD, 5NT, deoxycytidine kinase and MRP5 gene expression levels and their potential relation to dFdC and ara-C cytotoxicity are reviewed.
 ...
PMID:Genetic factors influencing pyrimidine-antagonist chemotherapy. 1604 92