JBC, Vol. 254, Issue 23, 11839-11846, Dec, 1979
The interaction of divalent copper and the microsomal electron transport system. A re-examination of the effects of copper chelates on the function of cytochrome P-450
J. Werringloer, S. Kawano, N. Chacos and R. W. Estabrook
Lipophilic chelates of divalent copper, possessing superoxide
dismutase-like activity, have been proposed to enhance the decay of
oxycytochrome P-450 to explain their inhibitory effect on microsomal
mixed-function oxidation reactions (Richter, C., Azzi, A., Weser, U., and
Wendel, A. (1977) J. Biol. Chem. 252, 5061-5066). The present
investigation, however, failed to provide evidence in favor of this
hypothesis. In particular, it was found that the reported inhibition of
cytochrome P-450-catalyzed hydroxylation reactions by copper-tyrosine is
associated with an inhibition rather than a stimulation of the formation of
hydrogen peroxide, the product of the dismutation of the superoxide
radicals generated as a result of the decay of oxycytochrome P-450. The
attenuation of both these reactions was shown to be the consequence of an
impaired function of the NADPH-cytochrome P-450 reductase. Additional sites
of interaction of copper chelates and the microsomal electron transport
system appear to exist since divalent copper was found to undergo reduction
reactions with NADPH and NADH as electron donors. These reduction reactions
do not involve superoxide radicals and, therefore, are unrelated to the
ability of copper chelates to function in a superoxide dismutase-like
manner.
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