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

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