A Salmonella typhimurium mutant dependent upon carbamyl aspartate for resistance to 5-fluorouracil is specifically affected in ubiquinone biosynthesis.
The isolation and properties of a mutant dependent upon exogenous carbamyl aspartate for resistance to 5-fluorouracil are described. The mutant was deficient in the synthesis of ubiquinone and accumulated a quinone provisionally identified as the ubiquinone precursor 2-octaprenyl-3-methyl-6-methoxy-1,4-benzoquinone. The mutation resulted in an alteration in the regulation of synthesis of enzymes involved in de novo pyrimidine biosynthesis but did not establish a functional block in dihydroorotate dehydrogenase activity in vivo. Conditional resistance to 5-fluorouracil apparently occurred through an inhibition of the conversion of the analog to the nucleotide level.
D002219:Carbamates / Q000378:metabolism; D004352:Drug Resistance, Microbial; D005472:Fluorouracil / Q000494:pharmacology*; D009154:Mutation; D012486:Salmonella typhimurium / Q000235:genetics* / Q000378:metabolism; D014451:Ubiquinone / Q000096:biosynthesis*; D014498:Uracil / Q000378:metabolism
D002219:Carbamates; D014451:Ubiquinone; D014498:Uracil; D005472:Fluorouracil