Arylamine N-acetyltransferase from fast (C57BL6) and slow (A/J) N-acetylating strains of mice.
Many drugs and xenobiotics which are arylamines or hydrazines are metabolized by N-acetyltransferase. The enzyme is polymorphically expressed in humans and inbred strains of laboratory animals can be classified as fast or slow acetylating strains. N-Acetyltransferase has been partially purified from livers from a fast acetylator, C57BL6, and a slow acetylator, A/J, strain of mouse. The enzyme has been purified 1900- and 955-fold, respectively from the two strains, but still represents less than 20% of the total protein. These studies show that at least 5000-fold purification is required to isolate mouse liver N-acetyltransferase from either strain. During purification, N-acetyltransferase from both strains of mice elute identically as a single peak on ion exchange chromatography. Sucrose density gradient centrifugation of N-acetyltransferase shows partial separation of the activity from A/J mice into two peaks whilst the enzyme from C57BL6 mice migrates as one peak which is distinct from both the major and minor types of N-acetyltransferase in A/J mouse liver. The hydrodynamic parameters of N-acetyltransferase from C57BL6 mice and the major peak of N-acetyltransferase from A/J mice show that these enzymes are likely to be monomers of apparent molecular weights 33,000 +/- 1000 and 30,000 +/- 2000, respectively. These results indicate that the N-acetyltransferase isozymes in liver of these two strains of mice are not identical.
Watson
A P
AP
Department of Pharmacology, University of Oxford, U.K.
Wang
P D
PD
Sim
E
E
D000123:Acetyltransferases / Q000302:isolation & purification*; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000302:isolation & purification*; D002499:Centrifugation, Density Gradient; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D003600:Cytosol / Q000201:enzymology; D004591:Electrophoresis, Polyacrylamide Gel; D008099:Liver / Q000201:enzymology*; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008970:Molecular Weight
D000123:Acetyltransferases; D001191:Arylamine N-Acetyltransferase