Oxidation of thiobenzamide by the FAD-containing and cytochrome P-450-dependent monooxygenases of liver and lung microsomes

Biochem Pharmacol. 1983 Nov 15;32(22):3419-28. doi: 10.1016/0006-2952(83)90371-4.


Two distinct microsomal pathways involved in the metabolism of thiobenzamide to thiobenzamide S-oxide have been identified and quantitated in the liver and lungs of mice and rats, using a highly inhibitory antibody against NADPH-cytochrome P-450 reductase. Approximately 50 and 65% of the oxidation in mouse and rat liver microsomes, respectively, was due to the FAD-containing monooxygenase, the remainder being catalyzed by cytochrome P-450. In the mouse lung, S-oxidation was predominantly via the FAD-containing monooxygenase while that in the rat lung was about 60% via the FAD-containing enzyme and 40% via cytochrome P-450. Cytochrome P-450-dependent S-oxidation of thiobenzamide was induced in the liver by treatment of mice with phenobarbital and slightly increased by treatment with 3-methylcholanthrene, while in rat liver either of these treatments caused only a small increase in metabolism due to cytochrome P-450. Thermal inactivation of the FAD-containing monooxygenase left the cytochrome P-450 component essentially unchanged. Thermally treated microsomes had a pH activity profile characteristic of cytochrome P-450 and were less inhibited by methimazole and thiourea when compared to untreated microsomes. Female mouse liver microsomes had a much higher, and female rat liver microsomes a lower, ability to S-oxidize thiobenzamide when compared to the males.

Publication types

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

MeSH terms

  • Amides / metabolism*
  • Animals
  • Cytochrome P-450 Enzyme System / metabolism*
  • Enzyme Induction
  • Female
  • Lung / enzymology*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Microsomes / enzymology
  • Microsomes, Liver / enzymology*
  • NADPH-Ferrihemoprotein Reductase / antagonists & inhibitors
  • Oxygenases / antagonists & inhibitors
  • Oxygenases / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Sex Factors
  • Thioamides / metabolism*


  • Amides
  • Thioamides
  • thiobenzamide
  • Cytochrome P-450 Enzyme System
  • Oxygenases
  • dimethylaniline monooxygenase (N-oxide forming)
  • NADPH-Ferrihemoprotein Reductase