Open AccessLigand Binding of Organic Sulfides to Microsomal Cytochrome P ‐450
Author(s) -
NASTAINZCYK Wolfgang,
RUF Hans Heinrich,
ULLRICH Volker
Publication year - 1975
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1975.tb21039.x
Subject(s) - chemistry , cytochrome , sodium dithionite , dithionite , ligand (biochemistry) , microsome , stereochemistry , substrate (aquarium) , sulfide , photochemistry , medicinal chemistry , inorganic chemistry , organic chemistry , enzyme , biochemistry , receptor , geology , oceanography
Octyl methyl‐, butyl methyl‐ and pentamethylene sulfide react with about 50 % of oxidized cyto‐chrome P‐450 in liver microsomes from phenobarbital‐pretreated rats by formation of optical dif‐ference spectra with maxima at 435 and 552 nm and concomitant shifts in the electron paramagnetic resonance spectrum. Reduction by NADPH or sodium dithionite yielded a Soret absorption band at 449 nm and α and β bands at 573 and 545 nm, respectively. The ligand metyrapone and the substrate n ‐octane competitively inhibited the formation of these difference spectra and pentamethylene sulfide was a strong competitive inhibitor of the O ‐dealkylation of 7‐ethoxycoumarin. These results indicate a direct ligand binding of the sulfides to cytochrome P ‐450 with concomitant blocking of the hydrophobic substrate binding site. Some sulfides did not interact as ligands but as substrates, in variation, however, with the source of microsomes.