N- and O-deacetylation of N-acetoxy-N-arylacetamides by mammalian hepatic microsomes.
The present study demonstrates that hepatic microsomes from guinea pigs, rats, mice, hamsters, rabbits and dogs catalyze N-deacetylation of N-hydroxy-2-acetylaminofluorene (N-OH-AAF) and N-hydroxy-3,2'-dimethyl-4-acetylaminobiphenyl and O-deacetylation of N-acetoxy-2-acetylaminofluorene (N-AcO-AAF) and N-acetoxy-3,2'-dimethyl-4-acetylaminobiphenyl (N-AcO-DMAABP). Gel filtration resolves the solubilized guinea pig microsomal enzymes into two deacetylases. The larger molecular weight enzyme catalyzes N-deacetylation of N-OH-AAF, whereas the smaller one cannot. Both enzymes catalyze O-deacetylation of N-AcO-AAF and N-AcO-DMAABP, but the activity is mainly due to the larger enzyme. Guinea pig and rat liver microsomes also catalyze N-deacetylation of N-AcO-AAF resulting in the binding of 2-aminofluorene to nucleic acids, but the activities are much less than that of the O-deacetylation of N-AcO-AAF. Thus, the amino-fluorene-DNA adducts which have been found in intact cells treated with N-AcO-AAF may result directly from N-deacetylation or indirectly from N,O-acetyltransfer following O-deacetylation.
Yamada
H
H
Department of Chemical Carcinogenesis, Michigan Cancer Foundation, Detroit 48201.
Lee
M S
MS
Wang
C Y
CY
D000081:Acetamides / Q000378:metabolism*; D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D006224:Cricetinae; D004285:Dogs; D006168:Guinea Pigs; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism*; D012343:RNA, Transfer; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000081:Acetamides; D012343:RNA, Transfer; D000581:Amidohydrolases