Unique properties of NADPH- and NADH-dependent metabolism of p-nitroanisole catalyzed by cytochrome P-450 isozyme 2 in pulmonary and hepatic microsomal preparations from rabbits

Chem Biol Interact. 1986 Feb;57(2):143-60. doi: 10.1016/0009-2797(86)90034-7.


Approximately 90% of the NADPH- and NADH-dependent O-demethylation of p-nitroanisole (PNA) in the hepatic microsomal fraction from phenobarbital (PB)-treated rabbits and in the pulmonary microsomal fraction from untreated rabbits is catalyzed by the same isozyme of cytochrome P-450. This isozyme of cytochrome P-450 catalyzes less than 60% of this reaction in the hepatic microsomal fraction from untreated rabbits. Antibodies to NADPH-cytochrome P-450 reductase inhibit NADPH-dependent metabolism of p-nitroanisole by about 90% but have no effect on NADH-dependent metabolism. Hepatic NADPH-dependent metabolism of pNA and reduction of cytochrome c are inhibited to the same extent with varying amounts of antibodies to NADPH cytochrome P-450 reductase. The same relationship between inhibition of monooxygenase and reductase activities is observed for the hepatic and pulmonary metabolism of benzphetamine and 7-ethoxycoumarin. In contrast, the relationship between inhibition of the pulmonary NADPH-dependent metabolism of pNA and reductase activity is biphasic; at 75% inhibition of reductase activity, metabolism of pNA is inhibited by less than 25%. For NADH-dependent metabolism of pNA, our results indicate that both electrons are transferred to cytochrome P-450 from cytochrome b5.

MeSH terms

  • Animals
  • Anisoles / metabolism*
  • Carbon Monoxide / pharmacology
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System / metabolism*
  • Cytochrome b Group / metabolism
  • Cytochromes b5
  • Electron Transport
  • Isoenzymes / metabolism
  • Lung / enzymology*
  • Male
  • Microsomes / enzymology
  • Microsomes, Liver* / enzymology
  • NAD / metabolism
  • NADP / metabolism
  • Oxidoreductases, O-Demethylating / antagonists & inhibitors
  • Oxidoreductases, O-Demethylating / metabolism
  • Rabbits


  • Anisoles
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome b Group
  • Isoenzymes
  • NAD
  • NADP
  • Carbon Monoxide
  • Cytochromes b5
  • Cytochrome P-450 Enzyme System
  • 4-nitroanisole O-demethylase
  • Oxidoreductases, O-Demethylating
  • 4-nitroanisole