Interaction of Cytochrome C Oxidase with Steroid Hormones.

Ilya P Oleynikov,Natalia V Azarkina,Tatiana V Vygodina,Alexander A Konstantinov

doi:10.3390/cells9102211

Abstract

Estradiol, testosterone and other steroid hormones inhibit cytochrome c oxidase (CcO) purified from bovine heart. The inhibition is strongly dependent on concentration of dodecyl-maltoside (DM) in the assay. The plots of Ki vs [DM] are linear for both estradiol and testosterone which may indicate an 1:1 stoichiometry competition between the hormones and the detergent. Binding of estradiol, but not of testosterone, brings about spectral shift of the oxidized CcO consistent with an effect on heme a33+. We presume that the hormones bind to CcO at the bile acid binding site described by Ferguson-Miller and collaborators. Estradiol is shown to inhibit intraprotein electron transfer between hemes a and a3. Notably, neither estradiol nor testosterone suppresses the peroxidase activity of CcO. Such a specific mode of action indicates that inhibition of CcO activity by the hormones is associated with impairing proton transfer via the K-proton channel.

Highlights

Cytochrome c oxidase (CcO) is a key enzyme of aerobic metabolism and of oxidative phosphorylation, in particular, providing living organisms with access to the usage of oxygen reduction energy
In this work we show that sex hormones, testosterone and estradiol, as well as several other steroid hormones can markedly inhibit activity of cytochrome c oxidase (CcO) purified from bovine heart mitochondria
Dodecyl-maltoside of “Sol-Grade” type was purchased from Anatrace (Maumee, OH, USA). pH-buffers and EDTA were from Amresco (Radnor, PA, USA). o-dianisidine dihydrochloride was from ICN Biomedicals Inc (Irvine, CA, USA)

Summary

Introduction

Cytochrome c oxidase (CcO) is a key enzyme of aerobic metabolism and of oxidative phosphorylation, in particular, providing living organisms with access to the usage of oxygen reduction energy (reviewed, [1,2,3]). It is conceivable that an enzyme of such high importance should be subject to thorough control at all levels of cell metabolism—biosynthesis, assembly and regulation of the assembled enzyme turnover in response to various intracellular stimuli, for example by signal molecules emerging in the cells. The latter type of regulation is suitable for in vitro biochemical studies. Kadenbach and his laboratory, for instance [4]) and gaseous ligands of the oxygen-reducing center (see the review by Cooper & Brown [5]) has been amply studied.

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