Scheme 1.

Models describe the inhibition of the respiratory chain by NO in competition with O₂. Shown are a minimal model (continuous-line-depicted reactions, model 1) and an extended model (continuous- and dashed-line-depicted reactions, model 2). k_NOon and k_O2app refer to rate constants describing the combination of NO and O₂ with the reduced cytochrome a₃–Cu_B site (Fe_a3²⁺–Cu_B⁺) of COX, respectively. k_NOoff refers to the release of NO from the reduced cytochrome a₃–Cu_B site. k_IV, first-order rate constant in model 1 and second-order rate constant in model 2, refers to the reduction of the cyt a₃–Cu_B site entailing the arrival to COX of electrons from the other mitochondrial complexes, via cytochrome c (cyt c). k_III, a first-order rate constant, refers to the reduction of cytochrome c in complex III. Fe_a3³⁺–Cu_B⁺–O₂ species aggregates the intermediate forms appearing in the COX catalytic cycle. Mass action kinetics were assumed, and simulations were carried out with gepasi (45) and plas (46).