Cytochrome P-450-dependent oxidative cleavage of 1-(tetrahydro-2-furanyl)-5-fluorouracil to 5-fluorouracil

Jpn J Pharmacol. 1984 Sep;36(1):43-9. doi: 10.1254/jjp.36.43.


Cytochrome P-450-dependent oxidative cleavage of 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT) was investigated in a reconstituted system containing purified phenobarbital-inducible cytochrome P-450 (P-450(1)) or 3-methylcholanthrene-inducible cytochrome P-450 (P-448(1)). FT was converted into 5-fluorouracil (5-FU) in the reconstituted system, and its rate was 71 pmol 5-FU formed/min/nmol P-4501 and 45 pmol 5-FU/min/nmol P-448(1). Cytochrome P-450, NADPH-cytochrome P-450 reductase and NADPH were required for 5-FU production. Inhibitors of cytochrome P-450 such as carbon monoxide and metyrapone markedly decreased the rate. FT was found to interact with the purified cytochrome P-450, causing a reverse type I spectral change. From these observations, we concluded that the hepatic microsomal cytochrome P-450-dependent mixed function oxidase system participates in the oxidative cleavage of FT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytochrome P-450 Enzyme System / metabolism*
  • Cytochrome P-450 Enzyme System / pharmacology
  • Fluorouracil / analogs & derivatives*
  • Fluorouracil / metabolism*
  • In Vitro Techniques
  • Kinetics
  • Male
  • Microsomes, Liver / metabolism
  • Oxidation-Reduction
  • Rabbits
  • Tegafur / metabolism*


  • Tegafur
  • Cytochrome P-450 Enzyme System
  • Fluorouracil