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 FeII porphyrin, which mimics heme a₃ 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 FeIII and CuII 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.