Investigations on the Spectral Interactions of Fusarin C with Rat Liver Microsomal Cytochrome P-450

Abstract

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.