- Kinetic solvent isotope effect in steady-state turnover by CYP19A1 suggests involvement of Compound 1 for both hydroxylation and aromatization steps
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CYP19A1, or human aromatase catalyzes the conversion of androgens to estrogens in a three-step reaction through the formation of 19-hydroxy and 19-aldehyde intermediates. While the first two steps of hydroxylation are thought to proceed through a high-valent iron-oxo species, controversy exists surrounding the identity of the reaction intermediate that catalyzes the lyase and aromatization reaction. We investigated the kinetic isotope effect on the steady-state turnover of Nanodisc-incorporated human CYP19A1 to explore the mechanisms of this reaction. Our experiments reveal a significant (~2.5) kinetic solvent isotope effect for the C10-C19 lyase reaction, similar to that of the first two hydroxylation steps (2.7 and 1.2). These data implicate the involvement of Compound 1 as a reactive intermediate in the final aromatization step of CYP19A1.
- Khatri, Yogan,Luthra, Abhinav,Duggal, Ruchia,Sligar, Stephen G.
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p. 3117 - 3122
(2014/11/08)
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- Chloroiron(III)-5,10,15,20-tetraarylporphinate/N-methylimidazole catalyzed oxidation of androst-4-en-3,17-dione by cumene hydroperoxide
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The oxidation of androst-4-en-3,17-dione with cumene hydroperoxide, catalyzed by chloroiron(III)-5,10,15,20-tetraarylporphinate/N-methyl-imidazole systems, was studied under different reaction conditions. The chloroiron(III)-5,10,15,20-tetra(2,6-dichlorophenyl)porphinate/N-methy limidazole system in dichloromethane was found to be the most effective system for the aromatization of the A ring of androst-4-en-3,17-dione.
- Vijayarahavan,Chauhan
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p. 6223 - 6226
(2007/10/02)
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