Bohr effect

**Definition:** Hemoglobin's affinity for O2 falls as pH falls (acidosis) or PCO2 rises. This shifts the oxyhemoglobin dissociation curve to the RIGHT (P50 increases), favoring release of O2 to tissues.

**Mechanism:** - H+ and CO2 bind hemoglobin and stabilize the deoxygenated (T, "taut") state, which has lower O2 affinity. - H+ protonates specific residues (e.g., the C-terminal His146 of the beta chains), forming salt bridges that stabilize the T state. - CO2 forms carbamate (carbaminohemoglobin) at the N-terminal amino groups, which also stabilizes the T state. - In tissues: metabolism produces CO2, which RBC carbonic anhydrase converts to H2CO3, then to H+ and HCO3-. The H+ binds Hb, promoting O2 release. Deoxy-Hb is a better buffer, so this also helps buffer the H+ (the Haldane effect, the reciprocal). - In lungs: CO2 is exhaled and pH rises. Hb shifts back toward the R ("relaxed") state with higher O2 affinity, which promotes O2 loading (a leftward shift).

**Factors that shift the curve RIGHT (decreased affinity, increased unloading):** mnemonic "ACE BATs, Right": - Acid (low pH) - CO2 (high) - Exercise - 2,3-BPG (2,3-DPG) increased - Altitude (via increased 2,3-BPG) - Temperature increased

**Factors that shift the curve LEFT (increased affinity):** low CO2, high pH (alkalosis), low temperature, low 2,3-BPG, HbF (binds 2,3-BPG poorly), carbon monoxide, methemoglobin.

**Bohr vs. Haldane (frequently tested together):** - Bohr: CO2 and H+ lower Hb's O2 affinity (promotes O2 unloading). - Haldane: O2 binding lowers Hb's affinity for CO2 and H+ (promotes CO2 unloading in the lungs). Deoxygenated Hb carries more CO2 and buffers more H+.

**Clinical significance:** - Exercising muscle (high CO2, lactic acid, heat) gets more O2 delivery because of the rightward shift. - Acidosis (e.g., DKA, lactic acidosis) causes a right shift. This helps tissue O2 delivery, but sustained acidosis also alters 2,3-BPG levels. - Alkalosis (e.g., hyperventilation) causes a left shift, so Hb holds O2 more tightly. This can contribute to tissue hypoxia and symptoms like cerebral vasoconstriction and lightheadedness. - Fetal circulation (the double Bohr effect): fetal CO2 and acid cross into maternal blood, raising maternal pH-dependent affinity and lowering it for maternal Hb (right shift), while the fetal side shifts left, which favors O2 transfer to the fetus. This is on top of HbF's low 2,3-BPG binding and higher O2 affinity. - Myoglobin has no cooperativity and shows no Bohr effect (hyperbolic curve, higher O2 affinity than Hb).

**Key board points:** - Right shift means increased P50, lower affinity, more O2 unloading. - Cooperativity (sigmoidal curve) comes from the T-to-R transition. The Bohr effect modulates that transition allosterically. - Distinguish a curve shift (affinity changes) from a change in O2 content (anemia, CO poisoning).