Using a functional enzyme model to understand the chemistry behind hydrogen sulfide induced hibernation

Abstract

The toxic gas H(2)S is produced by enzymes in the body. At moderate concentrations, H(2)S elicits physiological effects similar to hibernation. Herein, we describe experiments that imply that the phenomenon probably results from reversible inhibition of the enzyme cytochrome c oxidase (CcO), which reduces oxygen during respiration. A functional model of the oxygen-reducing site in CcO was used to explore the effects of H(2)S during respiration. Spectroscopic analyses showed that the model binds two molecules of H2S. The electro-catalytic reduction of oxygen is reversibly inhibited by H(2)S concentrations similar to those that induce hibernation. This phenomenon derives from a weak, reversible binding of H(2)S to the Fe(II) porphyrin, which mimics heme a(3) in CcO's active site. No inhibition of CcO is detected at lower H(2)S concentrations. Nevertheless, at lower concentrations, H(2)S could have other biological effects on CcO. For example, H(2)S rapidly reduces Fe(III) and Cu(II) in both the oxidized form of this functional model and in CcO itself. H(2)S also reduces CcO's biological reductant, cytochrome c, which normally derives its reducing equivalents from food metabolism. Consequently, it is speculated that H(2)S might also serve as a source of electrons during periods of hibernation when food supplies are low.