Three Gases, O2, NO, and H2S, Meet in the MItochondria
Professor James P. Collman - Stanford University
Vendredi 29/05/2009, 14h00
Amphithéâtre Daniel Dautreppe, CEA-Grenoble
At physiological pH and potential a synthetic model of the active site in the enzyme cytochrome c oxidase (CcO), catalyzes the 4-electron reduction of oxygen. This model is covalently attached to a self-assembled-monolayer (SAM) on a gold electrode. During catalytic oxygen reduction electron delivery through the SAM's liquid-crystalline film is rate limiting, similar to the situation in CcO. The model contains all of the essential components in CcO's active site: an Fe heme ("heme a3") fitted with a proximal imidazole ligand and an array of three distal imidazoles bound to copper ("Cu-b"). A phenol mimicing "tyrosine 244" is attached to one distal imidazole. All three redox-active components are required to minimize the production of partially-reduced-oxygen-species (PROS) during oxygen reduction. This functional CcO model demonstrates how CcO itself might tolerate the hormone NO, which is known to diffuse through the mitochondria. It is proposed that Cu-b delivers superoxide to NO bound to Fe in heme a3 forming peroxynitrite and then nitrate, which diffuses away. Another toxic gas, H2S, which is produced in our bodies, has exceptional biological effects: at moderate concentrations (~80 ppm) in a mouse, H2S induces a state similar to hibernation, lowering the animal's temperature and slowing respiration. Using our functional CcO model, we have demonstrated that at the same concentration range H2S can reversibly inhibit catalytic oxygen reduction.