ABSTRACT
The toxic mechanisms of action of carbon monoxide (CO) have held great scientific interest since C. Bernard first recognized that the gas produced tissue hypoxia by reversible combination with hemoglobin. This chapter summarizes the understanding of how CO interacts with hemoproteins in the body, beginning with the well-studied interactions of CO with hemoglobin and their effects on oxygen transport to tissue. It focuses on the results of a variety of experimental approaches in the literature to explain concepts and controversies about uptake of the gas by intracellular hemoproteins and their potential roles in histotoxicity produced by CO poisoning. The physiological principles derived from early animal studies about the mechanism of toxicity of CO were simple: CO produced tissue hypoxia by binding tightly to hemoglobin and preventing it from transporting oxygen and releasing it to the tissues. Hemoglobin avidly binds CO at the iron (II) center of the heme moiety of the molecule.
