Enzymatic deacetylation of N-hydroxy-2-acetylaminofluorene by liver microsomes.

Abstract

Summary N -Hydroxy-2-acetylaminofluorene was rapidly deacetylated by guinea pig liver and, to a lesser extent, by other guinea pig tissues examined. The enzyme activity was located in the microsomal fraction of the liver. The enzyme appeared to be stimulated by trisodium pentacyanoamine ferrate, and it was inhibited by SKF-525A (β-diethylaminoethyldiphenylpropyl acetate hydrochloride), by sodium fluoride, and by diethyl p -nitrophenyl phosphate. The inhibition by diethyl p -nitrophenyl phosphate was complete at a concentration of 10 -5 m. Chloride or magnesium ions did not have any effect on the activity of the microsomal enzyme. The rate of deacetylation of N -hydroxy-2-acetylaminofluorene by guinea pig liver microsomes was about 20 times the rate of deacetylation of the same substrate by rabbit liver microsomes and 75 times the rate found for rat lvier microsomes. The average activities found for the 3 species were: guinea pig, 3.48 µmoles of N -hydroxy-2-acetylaminofluorene deacetylated/hr/mg of microsomal protein; rabbit, 0.21 µmole/hr/mg protein; and rat, 0.05 µmole/hr/mg protein. The rates of deacetylation of N -hydroxy-2-acetylaminofluorene, 2-acetylaminofluorene, and acetanilide by guinea pig and rat liver microsomes were compared. The rate of deacetylation of N -hydroxy-2-acetylaminofluorene was 17 time the rate of deacetylation of either 2-acetylaminofluorene or acetanilide by guinea pig liver microsomes. The rate of deacetylation of acetanilide by rat liver microsomes was 20 times the rate of deacetylation of either N -hydroxy-2-acetylaminofluorene or 2-acetylaminofluorene in this species.