In hemoglobin, the conformational change involving a transition from the high-affinity state to the low-affinity state is primarily driven by ____________.

In hemoglobin, the conformational change from the high-affinity state to the low-affinity state is primarily driven by oxygen binding. When hemoglobin molecules bind to oxygen, a structural change is induced that enhances their affinity for more oxygen molecules, a process known as cooperative binding. This transition to the high-affinity state allows hemoglobin to efficiently pick up oxygen in the lungs.

Once hemoglobin reaches tissues where oxygen levels are lower, the release of oxygen occurs, which involves a transition to the low-affinity state. The release of oxygen facilitates the delivery of oxygen to the tissues that need it most. This process can be affected by factors like pH, CO2 levels, and temperature, but the initial trigger for the conformational shift and the transition to the lower affinity state is indeed the binding and subsequent release of oxygen.