Comparison of two monooxygenase systems with cytochrome P450 in filamentous fungus Rhizopus nigricans.
Besides the progesterone inducible steroid hydroxylase which catalyses the transformation of progesterone to 11alpha-hydroxyprogesterone the presence of another monooxygenase system in filamentous fungus Rhizopus nigricans (R. nigricans)--lanosterol demethylase was confirmed. Lanosterol demethylase was not inducible with progesterone. After subcellular fractionation both monooxygenase systems were found in microsomal fraction of fungus R. nigricans. To find out how to differentiate between the hydroxylase and demethylase systems the influence of inhibitors ketoconazole and metyrapone on both monooxygenase systems was studied. Both substances efficiently inhibited fungal steroid hydroxylase. Spectral studies used to characterize the interaction of inhibitors with cytochromes P450 showed that both inhibitors bind to induced fungal preparations whereas in noninduced fungal preparations interaction with P450 was found only with ketoconazole. This indicated the difference in interaction of the two inhibitors on both monooxygenase systems present in fungus R. nigricans.
Kunic
B
B
Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Slovenia.
Makovec
T
T
Breskvar
K
K
D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007654:Ketoconazole / Q000494:pharmacology; D010088:Oxidoreductases / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012233:Rhizopus / Q000201:enzymology*; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058886:Sterol 14-Demethylase
D004791:Enzyme Inhibitors; D011725:Pyridines; C013109:metapyrone; D011374:Progesterone; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D013250:Steroid Hydroxylases; D058886:Sterol 14-Demethylase; D007654:Ketoconazole