Cooperative effects on radical recombination in CYP3A4-catalyzed oxidation of the radical clock beta-thujone.

Yongying Jiang, Paul R Ortiz de Montellano

Index: ChemBioChem. 10(4) , 650-3, (2009)

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Abstract

The timing of the beta-thujone radical clock (see scheme) can be specifically altered by an allosteric effector. Progesterone, a well-documented CYP3A4 allosteric effector, was found to increase the yield of the unrearranged, C4-derived product of beta-thujone oxidation at the expense of the combined yields of all the rearranged C4-oxidized metabolites. The results demonstrate that the apparent radical recombination rate in the CYP3A4 hydroxylation of beta-thujone is accelerated by the progesterone heterotropic cooperativity.