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- W71769985 abstract "Stable type III optical difference spectra with dual Soret peaks at 427nm and 455nm are observed following incubation of many methylenedioxyphenyl (MDP) compounds with NADPH-fortified microsomal suspensions and are thought to represent inhibitory MDP-carbene complexes with ferrocytochrome P-450. Under similar conditions MDP compounds also generate carbon monoxide from the methylenic carbon of the MDP ring. Carbon monoxide production is correlated with the Hammett sigma constants of the aromatic substituent and appears to result from spontaneous breakdown of the 455nm spectral complex. Studies with both microsomal suspensions and reconstituted systems incorporating individual purified cytochrome P-450s have established that MDP compounds exhibit considerable selectivity in their inhibitory interactions with different forms of cytochrome P-450. MDP complexes with dual Soret peaks are formed only with cytochrome P-450 (phenobarbital-type). MDP complexes with cytochrome P-448 (3-methylcholanthrene-type) show only a 456nm spectral peak. Only reactions catalyzed by cytochrome P-450 are susceptible to inhibition by MDP compounds. It is concluded that the inhibitory activity of MDP compounds is closely associated with formation of the 427nm spectral complex and that the 455nm complex is of little or no significance to inhibition. These findings are discussed in terms of the possible nature and mechanism of the inhibitory interactions of MDP compounds with cytochrome P-450." @default.
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- W71769985 date "1983-01-01" @default.
- W71769985 modified "2023-10-18" @default.
- W71769985 title "MECHANISTIC STUDIES ON THE INHIBITION OF CYTOCHROME P-450-MEDIATED MIXED FUNCTION OXIDATION" @default.
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- W71769985 doi "https://doi.org/10.1016/b978-0-08-029224-3.50075-7" @default.
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