Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.4.1 (cytosine deaminase)
 747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Triploid and tetraploid Saccharomyces strains containing different combinations of a gua-1 mutant allele and the corresponding wild type were prepared. The cultivation of the different strains in media upon which the mutant fails to grow leads to a pronounced growth rate response to the dosage of the wild-type allele. Proportionality between the specific activity of the guanosine 5'-monophosphate synthetase and the wild-type dosage was reavealed. Inosine 5'-monophosphate dehydrogenase, the precursor enzyme in the pathway, is derepressed in a sigmoid manner when the wild-type dosage is reduced, whereas the activity of cytosine deaminase, investigated as a reference enzyme, is less affected.
J Bacteriol 1975 Dec
PMID:Gene dosage effects in polyploid strains of Saccharomyces cerevisiae containing gua-1 wild-type and mutant alleles. 110 68

Pyrimidine base and ribonucleoside catabolic enzyme activities of the two type strains of the Pseudomonas diminuta group were investigated for taxonomic classification purposes. The presence of the pyrimidine salvage enzyme nucleoside hydrolase was indicated in both type strains following thin-layer chromatographic analysis. The presence of the hydrolase was also confirmed by enzyme assay. In addition, the activities of the pyrimidine salvage enzymes dihydropyrimidine dehydrogenase and dihydropyrimidinase were measurable in cell-free extracts of both P. diminuta and P. vesicularis. An absence of cytosine deaminase activity was found when assaying extracts of the two type strains. Nucleoside hydrolase and dihydropyrimidine dehydrogenase levels in P. vesicularis were influenced by carbon source while dihydropyrimidinase activity was observed to increase after P. diminuta growth on dihydrothymine as a nitrogen source.
FEMS Microbiol Lett 1992 Dec 01
PMID:Pyrimidine base and ribonucleoside catabolic enzyme activities of the Pseudomonas diminuta group. 149 Jun 15

In humans, apolipoprotein (apo) B48 is synthesized in the intestine as an obligatory constituent of chylomicrons. Apolipoprotein B48 is identical to the amino-terminal 2152 amino acids (240 kDa) of apoB100 and is translated from an edited apoB mRNA in which codon 2153 has been converted from glutamine (CAA) to what is recognized as a premature stop codon (UAA). To determine whether the apoB mRNA editing in fact converts cytosine 6666 in codon 2153 to uracil, we incubated a synthetic apoB RNA containing 32P-labeled cytosines in an in vitro editing system prepared from rabbit enterocytes. The in vitro edited RNA was purified and digested to nucleoside 5'-monophosphates, which were analyzed on two-dimensional thin-layer chromatography. We found that the edited base co-migrated with authentic uridine 5'-monophosphate. Thus, cytosine 6666 is converted to uracil, most likely by a nucleotide-specific cytosine deaminase. To determine whether apoB mRNA editing occurs in cell lines that do not synthesize apoB, we stably transfected a high expression vector containing 354 base pairs of apoB sequence into 18 different cell lines. We found apoB mRNA editing activity in five osteosarcoma cell lines and one epidermoid cell line, none of which synthesizes any detectable apoB. Thus, apoB mRNA editing occurs in cell lines that do not synthesize apoB, which suggests that mRNA editing may be a common biological phenomenon in eukaryotic cells.
J Biol Chem 1990 Dec 25
PMID:Apolipoprotein B mRNA editing. Direct determination of the edited base and occurrence in non-apolipoprotein B-producing cell lines. 226 36

A novel metabolic pathway for the degradation of creatinine with N-methylhydantoin, N-carbamoylsarcosine and sarcosine as successive intermediates was found to operate in Pseudomonas putida 77 and many other microorganisms. Enzymes involved in this pathway were purified from cells of P. putida 77 and characterized. The first step, deimination of creatinine, is catalyzed by cytosine deaminase/creatinine deiminase. The following two steps, ring-opening of N-methylhydantoin and decarbamoylation of N-carbamoylsarcosine, are catalyzed by new enzymes, N-methylhydantoin amidohydrolase and N-carbamoylsarcosine amidohydrolase, respectively. The former requires ATP, Mg2+, and K+ for the hydrolysis and the reaction proceeds as follows: N-methylhydantoin + ATP + 2 H2O----N-carbamoylsarcosine + ADP + Pi. The latter catalyzes the following reaction; N-carbamoylsarcosine + H2O----sarcosine + NH3 + CO2. Sarcosine dehydrogenase was found to be the responsible enzyme for the oxidation of sarcosine to glycine in P. putida 77, but sarcosine oxidase was also found to be involved in this oxidation in several microorganisms. These enzymes were found to be useful tools for determination of creatinine.
Clin Chim Acta 1989 Dec 15
PMID:Microbial enzymes for creatinine assay: a review. 269 73

The maximal velocity of the reaction (Vmax) and the half-saturation constant (K0.5) values of the S. typhimurium cytosine deaminase were altered in the presence of its effectors, pyrophosphate and orotidine monophosphate. From the kinetics of orotidine monophosphate inhibition of cytosine deaminase, it was characterized as a mixed-type noncompetitive inhibitor.
Experientia 1985 Dec 15
PMID:Effect of pyrophosphate and orotidine monophosphate on cytosine deaminase regulatory properties. 300 Aug 14

Our laboratory and others have shown alternative splicing of up to ten exons at a discrete extracellular site to be primarily responsible for the generation of CD44 variant (CD44v) isoforms. Based on clear differences in the expression of these CD44v isoforms between normal and malignant tissues, we believe that elucidation of the mechanisms underlying the regulation of CD44 alternative splicing may provide a new gene therapeutic targeting approach based on CD44 pre-mRNA processing in vivo. This strategy incorporates utilization of CD44 alternative splicing control elements into a chimeric enzyme/prodrug therapy (CEPT), a novel modification of the virus-directed enzyme/prodrug therapy (VDEPT) approach for the treatment of brain metastases from tumors of systemic origin. As initial steps towards the development of a gene therapeutic approach based on targeting tumor cell expression of specific CD44v alternatively spliced isoforms, we have: (1) developed a novel in vivo assay system that allows the rapid analyses of potentially therapeutic CD44 alternative splicing minigene constructs; and (2) cloned the E. coli cytosine deaminase (CD) gene and fused its enzymatically active domain to alternatively spliced CD44 exons (CD44/CD). Deamination of cytosine by this CD44/CD chimeric fusion protein is demonstrated in E. coli cell lysates to be equal to that of wild type cytosine deaminase.
J Neurooncol 1995 Dec
PMID:Gene therapeutic approach to primary and metastatic brain tumors: I. CD44 variant pre-RNA alternative splicing as a CEPT control element. 875 Jan 90

Epstein-Barr virus (EBV)-positive lymphomas are frequent among immunosuppressed patients. We have examined the feasibility of killing EBV-immortalized B lymphocytes by gene transfer involving the use of "suicide" genes whose expression in target cells renders them susceptible to killing by a prodrug. We examined two gene/prodrug pairs: the Escherichia coli cytosine deaminase (CD) gene with the prodrug 5-fluorocytosine (5-FC), and the herpes simplex virus thymidine kinase (HSV-TK) gene with the prodrug ganciclovir. Retroviral vectors and drug selection were used to obtain CD or HSV-TK expression in cells. Both the CD/5-FC and the HSV-TK/ganciclovir combinations yielded substantial killing of EBV-immortalized B lymphocytes in vitro, although the CD/5-FC regimen had a significantly greater therapeutic margin than the HSV-TK/ganciclovir combination. The CD/5-FC pair, but not the HSV-TK/ganciclovir pair, was shown to have a "bystander killing effect" in vitro. When only 30% of the cells expressed the suicide gene, scid mouse tumors regressed in both the CD/5-FC regimen and the HSV-TK/ganciclovir regimen, documenting an in vivo bystander effect with both regimens. However, a greater percentage of tumors completely regressed with the CD/5-FC regimen. Overall, the sum of our data indicates that the CD/5-FC combination is the more promising regimen for treatment of EBV-associated lymphomas in vivo.
Hum Gene Ther 1996 Dec 01
PMID:Killing Epstein-Barr virus-positive B lymphocytes by gene therapy: comparing the efficacy of cytosine deaminase and herpes simplex virus thymidine kinase. 895 14

A negative selection system for glioma gene therapy was established in vitro. C 6 rat glioma cells were infected with recombined retrovirus which contain Escherichia coli cytosine deaminase (EC-CD) gene. The enzyme CD can transform the non-toxic prodrug 5-Fluorocytosine (5-FC) to the highly cellular toxic compound 5-Fluorouracil (5-FU). The growth inhibition studies proved that CD-positive cells were highly sensitive to 5-FC, the IC50 about 3 mumol/L, compared with an IC50 of approximately 6000 mumol/L in parental C 6 cells. Both CD-positive and negative cells were sensitive to 5-FU at very low concentration (IC50 < 1 mumol/L). Mixed cellular assay showed CD-positive cells had "bystander effect" on CD-negative cells when exposed to 5-FC. Our results demonstrate that EC-CD gene should be an efficient suicide gene for the treatment of glioma.
Shi Yan Sheng Wu Xue Bao 1996 Dec
PMID:[Experimental treatment of brain tumor cells using CD suicide gene]. 977 83

The effect of the aging on the activities of enzymes involved in UMP-CMP metabolism were evaluated in the heart of newborn (1-day-old), young (20-day-old), adult (12-month-old), and aged (30-month-old) chickens. In newborn animals, UMP metabolism proceeds preferentially towards cytidine compounds rather than to breakdown. In addition, two pathways different from those involved in de novo synthesis may contribute to the synthesis of UMP: one, through cytosine deaminase that shows its maximal activity; the other, by uridine kinase, the main "salvage" enzyme of pyrimidine nucleotides. In young chickens, pyrimidine metabolism regards especially UMP. In fact, the lower activities of cytidylate phosphatase and cytosine deaminase, together with the remarkable increase of uridine kinase indicate that the metabolic flux converges on the main salvage pathway. In adult chickens, pyrimidine catabolism is enhanced, as supported by the maximal activity of the enzymes involved in UMP-CMP breakdown. On the contrary, the remarkable reduction of the anabolic enzymes suggests a limited resort to the salvage pathways. Finally, in aged chickens a reduced pyrimidine catabolism and a greater utilization of the salvage pathways appear to take place, thus contributing to the maintenance of pyrimidine nucleotide pool.
Biochem Mol Biol Int 1998 Dec
PMID:Influence of age on enzyme activities of pyrimidine metabolism in the chicken heart. 989 51

Recent evidence has suggested that tumor cells having a wild-type p53 status are more sensitive to chemotherapeutic agents and radiation than cells that lack functional p53. The heightened sensitivity of wild-type p53 cells is thought to be attributable to their propensity to undergo p53-mediated apoptosis after insult. Given that suicide gene therapy is essentially tumor-targeted chemotherapy, we examined the hypothesis that coexpression of wild-type p53 could enhance the efficacy of adenovirus-mediated suicide gene therapy. Human Hep3B and SK-OV-3 cells, which are null for p53, were infected with a pair of replication-deficient adenoviruses that expressed a cytosine deaminase/herpes simplex virus thymidine kinase (CD/HSV-1 TK) fusion gene without (fusion gene nonreplicative adenovirus, FGNR) or with (FGNRp53) the wild-type human p53 gene. The sensitivity of cells to the CD/5-fluorocytosine (CD/5-FC) and HSV-1 TK/ ganciclovir (GCV) enzyme/prodrug systems was determined in vitro and in vivo. Coexpression of p53 did not enhance the cytotoxicity of either the CD/5-FC or HSV-1 TK/GCV system in vitro. The failure to observe an effect of p53 could not be explained on the basis of insufficient or transient p53 expression, because FGNRp53-infected cells growth arrested in G1, induced Bax, and underwent apoptosis at an increased rate after prodrug treatment, particularly when the adenovirus E1A protein was present. Intratumoral injection of FGNRp53 concomitant with single or double pro-drug therapy resulted in a tumor growth delay that was equal to or less than that observed with the FGNR virus. Our results indicate that coexpression of p53 may not necessarily improve the efficacy of adenovirus-mediated CD/ 5-FC and HSV-1 TK/GCV suicide gene therapies in vivo.
Clin Cancer Res 1999 Dec
PMID:Efficacy of adenovirus-mediated CD/5-FC and HSV-1 thymidine kinase/ganciclovir suicide gene therapies concomitant with p53 gene therapy. 1063 64


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