Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

A mechanism is proposed for the formation of Ebg-evolved beta galactosidase-of E. coli based on the following assumptions: 1. In the presence of lactose, certain proteins being translated bind to their m-RNA-ribosome complexes; 2. This binding interferes with the release of m-RNA from the bacterial chromosome, marking the gene; 3. Thereupon a cytosine specific methylase and methyl cytosine deaminase pair, modify - mutate - the marked gene; 4. The result, after five or so mutations, is a new gene capable of coding for a different protein which can split lactose; 5. I propose that this enzyme pair has evolved to produce mutations internally, when need arises, as is the case here; 6. This may be a general mechanism through which drug resistance and detoxification of a novel chemical, could be achieved in bacteria; 7. All of these ideas are experimentally testable.
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PMID:Probable mechanism of enzyme evolution: how did EBG of E. coli originate? 11

Previous work has suggested that 1-beta-D-arabinofuranosylcytosine 5'-triphosphate is the active metabolite of 1-beta-D-arabinofuranosylcytosine. The amount of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate formed in tissues has been shown to be influenced by the relative levels of deoxycytidine kinase and cytosine deaminase. In this study we have measured the intracellular levels of deoxycytidine kinase and cytosine deaminase activities in synchronized cultures of normal rat kidney cells. The deoxycytidine kinase activity was found to be cell cycle related with a minor peak of activity in early G1 phase and a major peak of activity in middle and late S phase. The cytosine deaminase activity was also found to be cycle dependent with a peak of activity at G1 phase and another at S phase of the cell cycle. Similar results were obtained when cytosine deaminase activities were measured with cytidine, deoxycytidine, or 1-beta-D-arabinofuranosylcytosine as substrate. Present studies also confirmed earlier studies by other workers that the main effect of 1-beta-D-arabinofuranosylcytosine is in the late S phase of the cell cycle.
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PMID:Deoxycytidine kinase and cytosine nucleoside deaminase activities in synchronized cultures of normal rat kidney cells. 67 82

Uptake and intracellular transformation of pyrimidines supplying cells of the yeast Rhodotorula glutinis with nitrogen have been studied. The amine nitrogen of cytosine was found to be the easiest to utilize. The presence in the medium of inorganic ammonia along with cytosine had a slight effect on cytosine deaminase (EC 3.5.4.1) activity. The uracil produced entered into the nutrient medium with no fission break of the pyridmidine ring. In the absence of any other source of nitrogen, the cells of the yeast R. glutinis utilized nitrogen of the pyrimidine ring of oxypyrimidines. Catabolism of uracil followed the reductive pattern, with release of carbon dioxide; this was accompanied by synthesis of the key enzyme of pyrimidine catabolism, dihydrouracil dehydrogenase (EC 1.3.1.1), whose activity rose 10-fold. With thymidne as the sole source of nitrogen, the lag-phase growth of the yeast cells was maximum. Catabolism of the pyrimidine ring of thymine was possibly preceded by its transformation into uracil. With no source of nitrogen easily utilized, the uridine 5'-monophosphate content in the generally acid-soluble pool rose. Our discussion of the regulation of catabolism of exogenous pyrimidine bases by the yeast R. glutinis takes into account the fact that transformations of pyrimidine bases are determined by how easily the cells can use a particular base as a source of nitrogen.
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PMID:Utilization of exogenous pyrimidines as a source of nitrogen by cells of the yeast Rhodotorula glutinis. 94 62

Mode of action of 5-fluorocytosine (5-FC) and mechanisms of resistance to the drug are discussed on the basis of experiments performed with Candida albicans ATCC 26790 and with 50 selected clinical isolates of C. albicans belonging to serological type A or B and representing various degrees and models of 5-FC resistance (sensitivity). Incorporation of 5-fluorouridylic acid into RNA appeared as a prerequisite to antifungal activity, although at a given incorporation rate, growth inhibition varied considerably from one strain to the other. The amino acid pool was unbalanced, and there was evidence for disturbance of protein synthesis. These dysfunctions of RNA probably account for growth inhibition and cell death, whereas up to the present, there was no proof of formation of 5-fluorodeoxyuridylic acid nor of subsequent inhibition of thymidylate synthetase. Incorporation of fluorinated pyrimidine into RNA was lower in normally sensitive type B strains than in normally sensitive ones of type A, whereas the frequency of 5-FC-resistant mutants was the same. The two serological types did not differ in the activity of cytosine permease nor in that of cytosine deaminase. Among 29 clinical isolates with 6-FC resistance (or impaired sensitivity) no instance of cytosine permease deficiency was found. Two isolates (belonging to the serological type A) were deficient in cytosine deaminase, whereas the majority was probably deficient in uridine monophosphate pyrophosphorylase or had a surplus of de novo synthesis of pyrimidines. Relative 5-FC resistance was more common than complete resistance.
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PMID:Mode of action of 5-fluorocytosine and mechanisms of resistance. 109 64

The regulatory gene (argR) for the arginine biosynthetic pathway has been located at 106 min on the chromosome of S. typhimurium. In addition, the location of the gene specifying cytosine deaminase (cod) has been more precisely determined.
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PMID:Location of the argR gene on the chromosome of Salmonella typhimurium. 110 41

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.
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PMID:Gene dosage effects in polyploid strains of Saccharomyces cerevisiae containing gua-1 wild-type and mutant alleles. 110 68

Incorporation of labelled 14C-pyrimidines and 5-fluoropyrimidines (5-FC and 5-FU) in four different phenotypes of wild strains of Candida isolated from man showed comparable results to those obtained by the minimal inhibition concentration (MIC) test. Kinetics studies demonstrated significant rates of incorporation after 24 hours of culture in each case. It was also possible to infer the biochemical mechanisms of resistance to 5-FC, namely a defect in UMP pyrophosphorylase, cytosine deaminase and 5-FU permease in the ease of the following phenotypes: 5-FCR 5-FUR, 5-FCR 5-FUS and 5-FCS 5-FUR (R = resistant; S = sensitive). In this study, the permeation process was approached by a consumption assay which determined the rate of labelled substrates into the medium before and after 24 hours of culture. Thus, it was found that the consumption levels of the phenotype 5-FCS 5-FUS were very high, while those of the phenotype 5-FCR 5-FUR were minimal. The 5-FCS 5-FU5 phenotype had no detectable consumption of 5-FU. With regard to the 5-FC5 5-FUS phenotype, it seems that the non-incorporation of 5-FC into the RNAs after the consumption by the yeasts has a feed back effect on the permeation process.
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PMID:Sensitivity and resistance of pathogenic yeasts to 5-fluoropyrimidines. II.--Mechanisms of resistance to 5-fluorocytosine (5-FC) and 5-fluorouracil (5-FU) (author's transl). 121 21

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.
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PMID:Pyrimidine base and ribonucleoside catabolic enzyme activities of the Pseudomonas diminuta group. 149 Jun 15

The nucleotide sequence of a 3.1 kb segment carrying the cytosine deaminase gene (codA) from Escherichia coli was determined. The sequence revealed the presence of two open reading frames, the first (codB) specifying a highly hydrophobic polypeptide and the second specifying cytosine deaminase. A two-codon overlap between the two reading frames indicates that they constitute an operon. Transcription of the operon was found to be regulated by exogenous purines. Polypeptides specified by each of the two reading frames were expressed in minicells, and the codB gene product was found to be highly enriched in the membrane fraction. Uptake experiments showed that the CodB protein is required for cytosine transport into the cell and that the intracellular accumulation of cytosine correlated with the codB gene dose. A topological model for the cytosine permease in the cytoplasmic membrane is proposed.
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PMID:Characterization of the Escherichia coli codBA operon encoding cytosine permease and cytosine deaminase. 164 Aug 34

Expression of the bacterial gene for cytosine deaminase (CD; EC 3.5.4.1) in mammalian cells was evaluated as a negative selection system or suicide vector for potential use in gene transfer studies and therapies. Mammalian cells, unlike certain bacteria and fungi, do not contain the enzyme CD and do not ordinarily metabolize cytosine to uracil. Nor do they metabolize the innocuous compound 5-fluorocytosine to the highly toxic compound 5-fluorouracil. The Escherichia coli CD gene underwent PCR oligonucleotide-directed mutagenesis to enhance its expression in a eukaryotic system and it was then cloned into an expression vector, pLXSN, that also contains a neomycin-resistance gene. Murine fibroblast lines were transfected with the plasmid and subjected to brief selection in the neomycin analogue G418. Lysates from these cell populations exhibited significant CD activity detected by conversion of radiolabeled cytosine to uracil. In clonogenic assays transfected cells expressing CD were selectively killed by incubation in 5-fluorocytosine, whereas control cell lines were not. Dose-response studies evaluating [3H]thymidine incorporation or cloning efficiency demonstrated profound inhibition at and above 65 micrograms of 5-fluorocytosine per ml. Mixed cellular assays showed that CD-positive cells could be eliminated without bystander killing of other cells. Retrovirus-mediated CD gene transfer into various tissues was also demonstrated. Thus CD, with its ability to produce the toxic antimetabolite 5-fluorouracil from 5-fluorocytosine, may be useful as a negative selection system for studies and treatments employing gene transfer techniques.
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PMID:Transfer of the bacterial gene for cytosine deaminase to mammalian cells confers lethal sensitivity to 5-fluorocytosine: a negative selection system. 172 3


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