Pathology Thread

Hemoglobin (Hgb) is a large protein (66.7 kD) coupledto four porphyrins or heme moities.The globin portion of Hgb consists of four polypeptide chains ( a with 141aa and ß with 146aa )arranged in pairs forming a tetramer. Each globin chain is covalently attached to a heme moiety.

The bonds between a and ß chains are weaker than between similar globin chains, forming a natural cleavage plane, the a₁ß₂ interface, important for oxygen binding and release.

When this cleavage is open [R (relaxed) state] oxygen can bind (high oxygen affinity). When the two a₁ß₂ interfaces are closely bound [T (taut) state] the Hgb molecule has a low affinity for oxygen.

The binding of oxygen rotates the globin chains, moving the ß chains together and sliding the a₁ß₂ interfaces apart (the R state) thus increasing the oxygen affinity of Hgb.

Hemoglobin must bind O₂ at high O₂ tension and release it at low O₂ tension.

With deoxygenation the a₁ß₂ interface tightens lessening the affinity of Hgb for oxygen. This conformation is stabilized by proton binding and 2,3-DPG.

Decreasing pH strengthens the a₁ß₂ interface, stabilizing the low-affinity (T) conformation and releasing O₂ . This is the Bohr effect.

2,3-DPG binds to hemoglobin, forming a link at the a₁ß₂ interface. This results in a stable low affinity (T) conformation promoting the release of O₂ . 2,3-DPG also lowers the pH.

Where the O tension is low, as in the venous blood, the Bohr effect and 2,3-DPG combine to reduce the affinity of Hgb for O , releasing O to tissues.

What happens in the lung?