Abstract
The pathways by which uracil, cytosine, uridine, cytidine, deoxyuridine, and deoxycytidine are metabolized by Salmonella typhimurium are established. The various 5-fluoropyrimidine analogues are shown to exert their toxic effects only after having been converted to the nucleotide level, and these conversions are shown to be catalyzed by the same enzymes which similarly convert the natural substrates. Methods for isolating mutant strains blocked in various steps of metabolism of pyrimidine bases and nucleosides are described.
MeSH Terms
Aminohydrolases/analysis
Cytidine/metabolism
Cytosine/metabolism
Deoxyuridine/metabolism
Floxuridine/pharmacology
Flucytosine/pharmacology
Fluorouracil/pharmacology
Genetics, Microbial
Genotype
Mutation
Nucleosides/metabolism
Nucleotidyltransferases/analysis
Pentosyltransferases/analysis
Phosphotransferases/analysis
Pyrimidines/metabolism
Salmonella typhimurium/drug effects,growth & development,metabolism
Thymidine
Uracil/metabolism
Uracil Nucleotides
Uridine/metabolism
Chemicals
Nucleosides
Pyrimidines
Uracil Nucleotides
Floxuridine
Uracil
Cytidine
Cytosine
Flucytosine
Pentosyltransferases
Phosphotransferases
Nucleotidyltransferases
Aminohydrolases
Fluorouracil
Thymidine
Deoxyuridine
Uridine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Beck C F
Ingraham J L
Neuhard J
Thomassen E
References (23)
23 references, click to expand
-
Cold-sensitive mutations in Salmonella typhimurium which affect ribosome synthesis.
J Bacteriol. 1969 Mar;97(3):1298-304
PMID: 4887510
-
The metabolism of exogenously supplied nucleotides by Escherichia coli.
J Biol Chem. 1960 Feb;235:457-65
PMID: 14416749
-
The role of nucleoside phosphorylases in the degradation of deoxyribonucleosides by thymine-requiring mutants of E. coli.
Mol Gen Genet. 1971;110(4):289-98
PMID: 4930081
-
THE MODE OF ACTION OF 5-FLUOROURACIL AND ITS DERIVATIVES.
Proc Natl Acad Sci U S A. 1958 Oct 15;44(10):1004-12
PMID: 16590300
-
Massive incorporation of 5-fluorouracil into a bacterial ribonucleic acid.
Nature. 1959 Oct 17;184:1213-5
PMID: 14403183
-
Mutants of Salmonella typhimurium requiring cytidine for growth.
J Bacteriol. 1968 Jun;95(6):2431-3
PMID: 4876137
-
Purification and properties of a pyrimidine deoxyriboside phosphorylase from Escherichia coli.
Biochim Biophys Acta. 1958 Jun;28(3):562-6
PMID: 13560407
-
IMPROVED METHOD FOR THE ISOLATION OF THYMINE-REQUIRING MUTANTS OF ESCHERICHIA COLI.
J Bacteriol. 1965 Aug;90:554-5
PMID: 14329476
-
Pyrimidine nucleotide metabolism and pathways of thymidine triphosphate biosynthesis in Salmonella typhimurium.
J Bacteriol. 1968 Nov;96(5):1519-27
PMID: 4882015
-
Utilization of purine and pyrimidine compounds in nucleic acid synthesis by Escherichia coli.
Biochim Biophys Acta. 1954 Mar;13(3):381-5
PMID: 13140351
-
Location on the chromosome of Salmonella typhimurium of genes governing pyrimidine metabolism.
Mol Gen Genet. 1971;111(4):303-16
PMID: 4936309
-
Induction of enzymes involed in the catabolism of deoxyribonucleosides and ribonucleosides in Escherichia coli K 12.
Eur J Biochem. 1971 Apr 30;19(4):533-8
PMID: 4931185
-
Specificity and efficiency of thymidine incorporation in Escherichia coli lacking thymidine phosphorylase.
J Bacteriol. 1969 Sep;99(3):681-7
PMID: 4905532
-
The utilization of exogenous pyrimidines and the recycling of uridine-5'-phosphate derivatives in Saccharomyces cerevisiae, as studied by means of mutants affected in pyrimidine uptake and metabolism.
Eur J Biochem. 1969 Dec;11(2):249-60
PMID: 4311780
-
Uridine-5'-monophosphate pyrophosphorylase activity from Escherichia coli.
FEBS Lett. 1969 Nov 12;5(3):211-213
PMID: 11947279
-
A map of four genes specifying enzymes involved in catabolism of nucleosides and deoxynucleosides in Escherichia coli.
Mol Gen Genet. 1969 Aug 15;104(4):351-9
PMID: 4904508
-
Protein measurement with the Folin phenol reagent.
J Biol Chem. 1951 Nov;193(1):265-75
PMID: 14907713
-
FEEDBACK INHIBITION OF URIDINE KINASE BY CYTIDINE TRIPHOSPHATE AND URIDINE TRIPHOSPHATE.
Biochim Biophys Acta. 1964 Nov 15;91:380-6
PMID: 14254009
-
ION-EXCHANGE CHROMATOGRAPHY OF NUCLEOTIDES ON POLY-(ETHYLENEIMINE)-CELLULOSE THIN LAYERS.
J Chromatogr. 1964 Oct;16:111-25
PMID: 14226338
-
Inability of Escherichia coli B to incorporate added deoxycytidine, deoxyandenosine, and deoxyguanosine into DNA.
Eur J Biochem. 1970 Nov;17(1):68-71
PMID: 4922330
-
DEOXYTHYMIDINE KINASE OF ESCHERICHIA COLI. I. PURIFICATION AND SOME PROPERTIES OF THE ENZYME.
J Biol Chem. 1964 Jan;239:269-74
PMID: 14114853
-
Current linkage map of Salmonella typhimurium.
Bacteriol Rev. 1970 Jun;34(2):176-93
PMID: 4918632
-
Pyrimidine metabolism in microorganisms.
Bacteriol Rev. 1970 Sep;34(3):278-343
PMID: 4919542