Metabolic reduction of 1-nitrosoadamantane by rabbit liver microsomes. Properties of a C-nitroso reductase system.
Washed microsomes from rabbit liver reduced 1-nitrosoadamantane to N-hydroxy-1-aminoadamantane in the presence of a cofactor solution under aerobic conditions; no further reduction of the hydroxylamino metabolite to 1-aminoadamantane (amantadine) occurred. Reduced pyridine nucleotide cofactors are needed for the metabolic reduction. The rate of formation of N-hydroxy-1-aminoadamantane depended upon the microsomal protein content, the time of incubation and the concentration of 1-nitrosoadamantane incubated. The metabolic reduction occurred in air as well as under nitrogen or carbon monoxide. Cupric chloride, mercuric chloride, cysteamine, FAD, and FMN decreased significantly the C-nitroso reductase. The properties of the C-nitroso reductase differed from those of other microsomal reductive pathways.
D000218:Adamantane / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D001952:Bridged-Ring Compounds / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D009603:Nitroso Compounds / Q000378:metabolism*; D011817:Rabbits
D001952:Bridged-Ring Compounds; D004791:Enzyme Inhibitors; D009603:Nitroso Compounds; C020782:1-nitrosoadamantane; D009247:NADH, NADPH Oxidoreductases; D000218:Adamantane