Stoichiometry of aminopyrine demethylation with and without NADH synergism
Jansson, I.; Schenkman, J.B.
Drug Metabolism and Disposition the Biological Fate of Chemicals 9(5): 461-465
1981
ISSN/ISBN: 0090-9556 PMID: 6117446 Document Number: 170679
The stoichiometry of aminopyrine demethylation by rat liver microsomes is examined. The stoichiometry corresponds with combined oxidase/mono-oxygenase activities, i.e., 1 NADPH:1 oxygen:1 product (HCHO + H2O2). NADH synergism of NADPH-supported aminopyrine demethylation is accompanied by a synergism of NADPH-supported hydrogen peroxide formation and a severalfold increase in NADH consumption, further suggesting a relationship between the oxidase and mono-oxygenase reactions. During synergism the rate of cytochrome b5 oxidation is increased severalfold over that when the hemoprotein is reduced in the presence of either pyridine nucleotide alone, in agreement with earlier reports. This increased rate of cytochrome b5 reoxidation approximates the sum of the increased rates of oxidase plus mono-oxygenase reactions (expressed in terms of reducing equivalents), but is less than the increased rate of NADH oxidation (also in reducing equivalents). The suggestion is made that the NADPH-supported reaction opens pathways of metabolism in which electrons from NADH can participate.