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.
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