Ribose-transfer activity from uridine to 5-fluorouracil in Ehrlich ascites tumor cells.
Anabolism of 5-fluorouracil (5-FU) in the presence of uracil was examined using the cell-free extract of Ehrlich ascites tumor cells. FU-nucleoside formation from 5-FU with ribose 1-phosphate (R-1-P) or 2'-deoxyribose 1-phosphate was not readily inhibited even by the addition of uracil at 100 times higher concentration than 5-FU. FU-nucleotide formation from 5-FU with R-1-P and adenosine 5'-triphosphate or with 5-phosphoribosyl 1-pyrophosphate was slightly reduced as the concentration of uracil was increased. It was also found that 5-fluorouridine (5-FUR) was produced by "nucleoside N-ribosyltransferase," transferring a ribose moiety from uridine (UR) to 5-FU directly. This activity might play a role in the preferential formation of 5-FUR. However, 5-fluoro-2'-deoxyuridine was not produced by directly transferring a deoxyribose moiety. On the basis of several column chromatographies and characterization of kinetics, pH dependency, and response to inhibitors, the enzyme protein of the ribosyltransferase could not be distinguished from that of the phosphorylase.
Nabeya
Y
Y
Second Department of Surgery, Chiba University School of Medicine.
Isono
K
K
Moriyama
Y
Y
Fujimura
S
S
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D002852:Chromatography, Ion Exchange; D003857:Deoxyuridine / Q000494:pharmacology; D005467:Floxuridine / Q000378:metabolism; D005472:Fluorouracil / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010430:Pentosyltransferases / Q000037:antagonists & inhibitors; D057845:Pyrimidine Phosphorylases; D012313:RNA / Q000378:metabolism; D012266:Ribose / Q000378:metabolism*; D013889:Thiouracil / Q000031:analogs & derivatives / Q000494:pharmacology; D014498:Uracil / Q000031:analogs & derivatives / Q000494:pharmacology*; D014543:Uridine Phosphorylase / Q000037:antagonists & inhibitors
D005467:Floxuridine; C034753:5-benzylacyclouridine; D014498:Uracil; D013889:Thiouracil; D012313:RNA; D012266:Ribose; D010430:Pentosyltransferases; D057845:Pyrimidine Phosphorylases; D014543:Uridine Phosphorylase; C019269:benzylthiouracil; D005472:Fluorouracil; D003857:Deoxyuridine