Hemoglobin-nitric oxide cooperativity: is NO the third respiratory ligand?

Through its cooperative binding mechanism, hemoglobin is an effective transporter of oxygen and carbon dioxide. Although data have recently been presented suggesting otherwise, the rate at which nitric oxide binds to hemoglobin is not cooperative. On the other hand, the rate at which nitric oxide dissociates from hemoglobin is cooperative so that, similar to the case of oxygen, the cooperativity in equilibrium ligand binding is manifested in the dissociation rate rather than the association rate. Two general factors that diminish the likelihood that hemoglobin transports nitric oxide are the slow dissociation rate of nitric oxide from hemoglobin and the very fast hemoglobin oxidation reaction, which converts nitric oxide to the inert molecule nitrate. Despite these factors the possibility that NO is delivered by hemoglobin under certain conditions or through more complicated mechanisms needs further study.