•As pH drops, side chains of histidine become protonated, the salt bridge with aspartate forms, and the T state is stabilized
•CO2 produced by catabolism in tissues; CO2 binds to N-terminus, and forms carbonic acid (HCO3- + H+ ←→ H2CO3)
•H+ from carbonic acid, lowers pH to 7.2
•2,3-BPG produced is byproduct of cells; binds to + pocket in middle of hemoglobin [- charged; stabilizes T state and lowers affinity]
•At higher altitude there is lower pressure, and curve shifts towards T state (equilibrium shifts towards T state); need time to adjust BPG levels
•Fetus has Y chain, similar to B chain in mother. His residue changed to Ser residue. Without + charge, can't bind BPG as well. Binding affinity is increased (p50 reduced). Also pressure in womb is higher; makes a good delivery system.
•Cigarette smoke contains CO, which competes with O2 to bind to hemoglobin. This lowers the percent of oxygen being bound by Hb and delivered to tissues.