On the nature of the cytochrome P450scc "ultimate oxidant": characterization of a productive radical intermediate.

Abstract:

:The electron paramagnetic (EPR) properties of a transient species detected during a cytochrome P450 (P450)-mediated peroxidative reaction have been compared with those of peroxidases Compound I and model metalloporphyrins. The reaction which was studied with cholesterol-specific P450scc and (20R)-20-hydroperoxycholesterol, occurred without enzyme denaturation. The resulting transient species, which reached its maximum after 50 s reaction, was characterized by a one-line EPR spectrum, g = 2.0035, delta 1/2 = 1.08 mT. The decay of this radical was concomitant with the production of (20R)-20,21-dihydroxycholesterol. The reaction (almost 100% yield) conserved the stereo-specificity of the natural pathway. We suggest this intermediate is a candidate for the in vivo ultimate oxidant in the P450-mediated hydroxylation process. The comparison of the observed EPR spectrum with those of peroxidase Compound I and related synthetic models allows us to propose a FeIV porphyrin II cation radical structure for the intermediate.

journal_name

Arch Biochem Biophys

authors

Larroque C,Lange R,Maurin L,Bienvenue A,van Lier JE

doi

10.1016/0003-9861(90)90104-7

subject

Has Abstract

pub_date

1990-10-01 00:00:00

pages

198-201

issue

1

eissn

0003-9861

issn

1096-0384

pii

0003-9861(90)90104-7

journal_volume

282

pub_type

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