Irreversible inhibition of the cytosolic metabolism of N-hydroxy-2-acetylaminofluorene by its glycolyl analog.
The glycolyl hydroxamic acid derivative of 2-aminofluorene was found to be a potent inhibitor of its own metabolism and the metabolism of N-hydroxy-2-acetylaminofluorene by rat liver cytosol. The inhibition was irreversible, as well as time and concentration dependent, which indicates a suicide-inhibition type of metabolism. There was a direct correlation between the inhibition of N-hydroxy-2-acetylaminofluorene disappearance and 2-acetylaminofluorene formation. In contrast, both the glycolyl and acetyl hydroxamic acid derivatives were metabolized to a similar extent by enzymes in the microsomal fraction.
Lim
L O
LO
Department of Food Science and Human Nutrition, University of Florida, Gainesville 32611.
Corbett
B R
BR
Corbett
M D
MD
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives*; D000818:Animals; D001711:Biotransformation; D003600:Cytosol / Q000378:metabolism*; D006881:Hydroxyacetylaminofluorene / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
C054220:N-hydroxy-2-glycolylaminofluorene; D006881:Hydroxyacetylaminofluorene; D015073:2-Acetylaminofluorene