Proposed model for allosteric regulation of nitrite reduction by deoxyhemoglobin. The rate of nitrite reduction by deoxyhemoglobin is proportional to the product of the deoxyheme concentration and the rate constant, the latter of which is determined by heme reduction potential being greater and having a more negative E_1/2. Deoxyheme concentration and heme reduction potential/rate constant are maximal at low and high oxygen fractional saturations, respectively, resulting in a maximal initial rate of nitrite reduction at approximately 50% fractional saturation (ie, P₅₀). Note that the precise relationship between heme redox potential and fractional saturation is not known. In the model, a linear dependence is approximated based on observations that the rate constant for nitrite-reduction increases linearly with fractional saturation. The points shown on figure are theoretical and are presented to illustrate the concept that the product of rate constant and deoxyhemoglobin concentration determine the initial rate. Also illustrated are hemoglobin conformations (using the symmetry model; for the sake of simplicity, conformations adhering to the sequential model are not shown and R-T transition is denoted as occurring between first and second oxygen binding steps) that are populated as a function of fractional saturation. Conformations highlighted in the gray box denote the proposed intermediates populated at intermediate fractional saturations that have increased nitrite reductase activities and available deoxyheme binding sites to maximally reduce nitrite to NO and stimulate vasodilation.