Biochemistry of nitrite-hemoglobin hypoxic vasodilation along the A1 to A5 arterioles. There exists a steady state anatomic location within the circulation from artery to vein that has the greatest concentration of R₃ tetramers (orange line bottom panel), which possess the maximal nitrite reductase activity. At this location, there would always exist an equilibrium rate constant for nitrite reduction (red line top panel and green line bottom panel) and an equilibrium concentration of nitrite and deoxyhemes (maximized in R₃ tetramer). As soon as one red cell moves downstream a new one would replace it, thus preserving the concentration of nitrite and R₃ hemoglobin at that anatomic position. Thus, there will be an increased nitrite reductase rate and increased NO concentration surrounding the blood vessel. The NO concentration should increase in a bell curve distribution from artery to vein according to the predicted rate for nitrite reduction. The anatomic position of this equilibrium NO concentration will be responsive to tissue metabolism and oxygen consumption by moving the R-to-T transition upstream or downstream. Note that the rate of a second-order reaction is determined by the product of the concentration of 2 reactants and the bimolecular rate constant. In this case, the nitrite concentration changes only a little as hemoglobin deoxygenates, the deoxyhemoglobin concentration increases dramatically (blue line top panel, brown line bottom panel), whereas the bimolecular rate constant decreases dramatically (red line top panel, green line bottom panel) as hemoglobin goes from the R-to-T conformation. So the product of bimolecular rate constant and deoxyheme concentration peaks from 60% to 40% hemoglobin oxygen saturation when the most R₃ tetramers are present. Figure was modified and reproduced from Gladwin et al^24,43  with permission.