Interaction between vitamin K3 and benzo(a)pyrene metabolism in uninduced microsomes

Int J Biochem. 1987;19(12):1173-9. doi: 10.1016/0020-711x(87)90099-1.

Abstract

1. Relationship between quinone recycling, glucuronidation and benzo(a)pyrene (BaP) oxygenation was investigated in uninduced mouse liver microsomes--native and modified by Fe3+.FeEDTA and/or superoxide (O2-.)-initiated lipid peroxidation. 2. A functional coupling between glucuronidation of reduced quinones and BaP metabolism, not discernible during BaP metabolism by native uninduced microsomes, was demonstrable in the presence of a model quinone, vitamin K3 (menadione). 3. Menadione inhibited BaP oxygenation in microsomal preparations, by siphoning off electrons from cytochrome P-450, while addition of UDPGA reversed this effect by glucuronidation of menadiol. 4. Fe3+.FeEDTA and/or O2-.-initiated lipid peroxidation decreased, to different extent, the microsomal enzymatic activities involved in quinone metabolism. The most sensitive was quinone reductase activity, which was reduced by 77%. Under peroxidative conditions menadione was a less effective inhibitor of BaP metabolism. 5. The important role of the balance between quinone reductase and UDP-glucuronyltransferase activities in the coupling with BaP oxygenation is discussed. A mechanism by which vitamin K3 could exert a regulatory effect on BaP metabolism is proposed.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Benzo(a)pyrene / metabolism*
  • Female
  • Kinetics
  • Lipid Peroxides / metabolism
  • Mice
  • Microsomes, Liver / metabolism*
  • Superoxides / metabolism
  • Uridine Diphosphate Glucuronic Acid / pharmacology
  • Vitamin K / pharmacology*

Substances

  • Lipid Peroxides
  • Superoxides
  • Vitamin K
  • Uridine Diphosphate Glucuronic Acid
  • Benzo(a)pyrene