Investigations on the spectral interactions of fusarin C with rat liver microsomal cytochrome P-450.
1. The spectral interaction of a mutagenic fungal metabolite, fusarin C, with rat liver microsomal cytochrome P-450 was investigated using a method which determines competitive inhibition between substrates eliciting the same type of spectral change. The strong u.v. absorption of fusarin C in the region where the spectral changes of cytochrome P-450 are monitored prevented direct binding studies. 2. The conversion of fusarin C to fusarin PM1 by the microsomal carboxylesterase was effectively inhibited by either decreasing the temperature during the binding studies or by addition of NaF (20 mM) during the enzymic inhibition investigations. 3. Fusarin C competitively inhibited the binding of the type II substrate aniline, yet the enzymic hydroxylation reaction of aniline was inhibited in a non-competitive manner. 4. Although the C-13/C-14 epoxide group of fusarin C is necessary for mutagenicity, an additional metabolic step is required. The present data indicated that fusarin C may interact with cytochrome P-450 in a similar way to aniline.
Gelderblom
W C
WC
Research Institute for Nutritional Diseases, South African Medical Research Council, Tygerberg.
Swart
P
P
Kramer
P S
PS
D020001:1-Butanol; D000818:Animals; D000440:Butanols / Q000494:pharmacology; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006591:Hexobarbital / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009153:Mutagens / Q000378:metabolism*; D011090:Polyenes / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012969:Sodium Fluoride / Q000494:pharmacology; D013053:Spectrophotometry
D000440:Butanols; D009153:Mutagens; D011090:Polyenes; D020001:1-Butanol; D012969:Sodium Fluoride; D003577:Cytochrome P-450 Enzyme System; D006591:Hexobarbital; C041403:fusarin C; D002265:Carboxylic Ester Hydrolases