Hemoglobin and mitochondrial effects of carbon monoxide

Normal: Hb binds oxygen and delivers it to peripheral tissue with low PO₂. Reduced cytochrome c (Cyt_C) transfers its electron (e–) to cytochrome c oxidase Subunit 1 (Cyt_A – binuclear center with heme a and Copper [Cu_A]). The electron reduces oxygen (O₂) at Subunit 2 (Cyt_A3 – binuclear center with heme a3 and Copper [Cu_B]), forming water and transporting a proton (H+) through the inner mitochondrial membrane.
CO toxicity: CO competitively binds to Hb with O₂, reducing total oxygen carrying capacity by: (1) preferentially binding to CO instead of O₂ (anemia like effect) and (2) stabilizes the relaxed quaternary state of Hb, that binds to O₂ with higher affinity and will not release it in low PO₂ environment. CO binds competitively with O₂ at the reduced heme a3 in Subunit 2. This causes: (1) inhibition of the reduction of O₂ to water (the end destination of electrons in the electron transport chain); (2) cessation of the transfer of H+ into the intermembrane space, shutting down ATP generation through ATP synthase; and (3) accumulation of electrons entering the electron transport chain through complexes I and III which can produce superoxide leading to deleterious effects.