DEFINITIONS

Bohr effect

• Low pH enhances hemoglobin oxygen dissociation

2, 3 Bisphosphoglycerate (BPG)

• Molecule localized in red blood cells
• Decreases hemoglobin’s oxygen affinity

DISSOCIATION CURVE

• % oxygen saturation vs. oxygen partial pressure (torr)
• Cooperative binding produces sigmoidal binding curve

Bohr Effect

• Decrease in blood pH shifts curve to the right
• Hemoglobin requires greater pO2 in peripheral tissues to reach 50% saturation
• Lowering pH decreases hemoglobin’s oxygen affinity

2,3 BPG

• Hemoglobin without 2,3 BPG: shifts curve to the left (hyperbolic like myoglobin)
• Adding 2,3 BPG: shifts curve back to the right.

BOHR EFFECT

Beta subunit

• Aspartate (-) and histidine (+)

T-form: histidine pKa = 8.0 (side chains close to each other)

• T-form favored when blood pH –> has a high affinity for H+

R-form: histidine pKa drops to 7.1 (side chains move apart)

• Histidine loses H+
• R-form favored when blood pH is high and H+ concentration is low

Carbon dioxide

• CO2 + H2O –> H2CO3 (carbonic acid) –> HCO3- (bicarbonate) + H+ (reversible)
• Carbonic anhydrase catalyzes carbonic acid formation
• Carbonic acid spontaneously loses proton to form bicarbonate
• Bicarbonate = blood buffer
• Increase in CO2 –> lowers blood pH –> favors T-form hemoglobin

Carbaminohemoglobin: CO2 binds N-terminal amino acids in hemoglobin

2,3 BPG

• Has strong negative charge: binds central cavity in hemoglobin
• Stabilizes the T-form (only binds T-form)

CARBON MONOXIDE

• Binds iron center with 220 times the affinity of O2 (irreversible)
• Permanently increases oxygen affinity of remaining heme groups for oxygen
• Decreases oxygen release in peripheral tissues

CLINICAL CORRELATION

Acetazolamide

• Carbonic anhydrase inhibitor used to treat altitude sickness
• Increases bicarbonate excretion by kidneys
• Makes blood more acidic, promotes oxygen release in peripheral tissues

High altitude conditions

• Individuals adapted to high altitude produce more 2,3 BPG
• Favors T-form hemoglobin and O2 release: more efficient O2 delivery

Tobacco smoke

• Smokers have elevated blood CO: hinders O2 delivery
• Can produce tissue hypoxia