Conference paper

The Heme Protein P450 from Adrenal Cortex: Its Reactivities in Ferric and Ferrous Forms

H. Schleyer ; Harrison Department of Surgical Research and Johnson Research Foundation, School of Medicine, University of Pennsylvania, Philadelphia, Pa. 19104, U.S.A.
D. Y. Cooper ; Harrison Department of Surgical Research and Johnson Research Foundation, School of Medicine, University of Pennsylvania, Philadelphia, Pa. 19104, U.S.A.
O. Rosenthal ; Harrison Department of Surgical Research and Johnson Research Foundation, School of Medicine, University of Pennsylvania, Philadelphia, Pa. 19104, U.S.A.
P. Cheung ; Harrison Department of Surgical Research and Johnson Research Foundation, School of Medicine, University of Pennsylvania, Philadelphia, Pa. 19104, U.S.A.

Abstract

In the course of this reaction cycle the heme protein undergoes a
series of changes of its coordination around the Fe (on reduction
to its »unliganded~ Fe2+ state, on binding of the 0 2 molecule, and
upon introduction of the second reducing equivalent, as the heme
protein returns to its original Fe3+ state}.
Steroid substrates, inhibitors, and a variety of agents bind to
the heme protein P450(Fe3+), isolated in a S = 1/2 form from bovine
adrenal glands, with high affinities at sites near the heme group,
but do not as a rule enter the coordination sphere of the Fe. This
leads to perturbations of the electronic structure which can be followed
by spectroscopic techniques (optical absorption, EPR spectroscopy)
in combination with suitable chemical methods. Direct replacement
of a ligand can also be achieved. The ferrous heme
protein P450(Fe2+), in its unliganded and liganded forms, was also
investigated. P450(Fe2•) combines readily with small ligands such
as 0 2 (418 nm), CO (448 nm), and nitric oxide. Larger lipophilic
molecules (e. g. pyridine derivatives, other heterocyclic compounds,
haloalkanes, or hydroperoxides) also bind readily to P450(Fe2+),
often with high affinities. They tend to enter the coordination
sphere of the Fe and form stable complexes often with distinct
optical absorption (440-470 nm); additional unspecific binding is
frequently observed.
Representative examples of the results for the various cases
of interactions are presented and are discussed in relation to a
hypothetical structure of P450(Fe3• ), S = 1/2, as a protoheme IX
complex, with a thiol-group and a N-containing group as axial
ligands; the observations are further related to the required changes
in coordination in the course of the hydroxylation reaction.

Keywords

Hrčak ID:

196359

URI

https://hrcak.srce.hr/196359

Publication date:

30.3.1977.

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