Flavoenzymes inhibited by indomethacin.
The effect of indomethacin on the activity of five different flavoenzymes, three dehydrogenases and six hydrosases, was determined. Indomethacin at concentration 1.0 mM inhibited the activity, in decreasing order of sensitivity, of the following flavoenzymes: D-amino acid oxidase (pig kidney), flavin-containing monooxygenases (pig liver microsomal), cyclohexanone monooxygenase (Acinetobacter), NADPH-quinone reductase (pig liver), and glutathione reductase (yeast), but it had no effect on the activity of glucose oxidase (Aspergillus) or liver microsomal NADPH-cytochrome P-450 reductase. Indomethacin was competitive with D-alanine for the D-amino acid oxidase (Ki=30 microM) and with NADPH for all other flavoenzymes sensitive to this compound (Kis 170-500 microM). While indomethacin also inhibited two of the three NAD(P)+-dependent dehydrogenases tested, the Kis were relatively high (<1, 500 microM), and of the six different hydrolases tested only one, liver microsomal esterase, was inhibited by indomethacin (Ki=600 microM). Indomethacin also inhibited aminopyrine demethylation catalyzed by the liver microsomal P-450 monooxygenase (Ki=1,000 microM). Although the exact mechanism for the inhibition of functionally different flavoenzymes sensitive to indomethacin is not known, the inhibition is probably not due to the detergent properties of this drug.
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005415:Flavins / Q000378:metabolism*; D006867:Hydrolases / Q000037:antagonists & inhibitors; D007213:Indomethacin / Q000494:pharmacology*; D007700:Kinetics; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D009252:NADPH Dehydrogenase / Q000037:antagonists & inhibitors
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D005415:Flavins; D006899:Mixed Function Oxygenases; D009252:NADPH Dehydrogenase; D006867:Hydrolases; D007213:Indomethacin