Hemoglobin and mitochondrial effects of carbon monoxide
Hemoglobin and mitochondrial effects of carbon monoxide
Normal: Hb binds oxygen and delivers it to peripheral tissue with low PO2. Reduced cytochrome c (CytC) transfers its electron (e–) to cytochrome c oxidase Subunit 1 (CytA – binuclear center with heme a and Copper [CuA]). The electron reduces oxygen (O2) at Subunit 2 (CytA3 – binuclear center with heme a3 and Copper [CuB]), 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.