TY - JOUR
T1 - Mechanism of 2-naphthylamine oxidation catalysed by pig liver microsomes
AU - Poulsen, Lawrence L.
AU - Masters, Bettie Sue Siler
AU - Ziegler, Daniel M.
N1 - Funding Information:
This work carried out during tenure of one of us (DMZ) on a U.S. Public Health Service Career Development Award (l-K3-GM-25990). The parts of this study carried out at the Health Science Center at Dallas under the direction of B.S.S. Masters, were supported by U.S. Public Health Service Grant No. HLI 13619 and Grant No. 1-453 from the Robert A. Welch Foundation.
PY - 1976
Y1 - 1976
N2 - 1. In pig liver microsomes 2-naphthylamine-dependent NADPH oxidation, oxygen reduction, and hydroxylamine formation are linear with time for several minutes. A sharp increase in NADPH oxidation and oxygen uptake then coincides with an abrupt loss of hydroxylamine from the medium. 2. The initial rate of 2-naphthylamine N-oxidation correlates with the micro-somal concentration of mixed-function amine oxidase and the extent of linear accumulation of hydroxylamine is dependent on microsomal NADPH-cyto-chrome c reductase activity and concentration of lipid (microsomes). 3. Antisera to NADPH-cytochrome c reductase markedly decreased hydroxylamine accumulation during incubation but had no effect on the rate of 2-naphthylamine N-oxidation. 4. A system duplicating all of the kinetic properties of the microsomal 2-naphthylamine oxidase was constructed with two purified flavoproteins, (mixed-function amine oxidase and NADPH-cytochrome c reductase) and a lipid phase (erythrocyte ghosts or synthetic lecithin liposomes). 5. By independently varying the concentrations of each component in the reconstituted system, the contribution of each to the observed kinetics was defined. 6. In addition to the initial JV-oxidation of 2-naphthylamine, at least six other reactions contribute to the kinetic patterns of 2-naphthylamine oxidation catalysed by the reconstituted system.
AB - 1. In pig liver microsomes 2-naphthylamine-dependent NADPH oxidation, oxygen reduction, and hydroxylamine formation are linear with time for several minutes. A sharp increase in NADPH oxidation and oxygen uptake then coincides with an abrupt loss of hydroxylamine from the medium. 2. The initial rate of 2-naphthylamine N-oxidation correlates with the micro-somal concentration of mixed-function amine oxidase and the extent of linear accumulation of hydroxylamine is dependent on microsomal NADPH-cyto-chrome c reductase activity and concentration of lipid (microsomes). 3. Antisera to NADPH-cytochrome c reductase markedly decreased hydroxylamine accumulation during incubation but had no effect on the rate of 2-naphthylamine N-oxidation. 4. A system duplicating all of the kinetic properties of the microsomal 2-naphthylamine oxidase was constructed with two purified flavoproteins, (mixed-function amine oxidase and NADPH-cytochrome c reductase) and a lipid phase (erythrocyte ghosts or synthetic lecithin liposomes). 5. By independently varying the concentrations of each component in the reconstituted system, the contribution of each to the observed kinetics was defined. 6. In addition to the initial JV-oxidation of 2-naphthylamine, at least six other reactions contribute to the kinetic patterns of 2-naphthylamine oxidation catalysed by the reconstituted system.
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U2 - 10.3109/00498257609151661
DO - 10.3109/00498257609151661
M3 - Article
C2 - 10687
AN - SCOPUS:0017175198
VL - 6
SP - 481
EP - 498
JO - Xenobiotica
JF - Xenobiotica
SN - 0049-8254
IS - 8
ER -