Special Focus 475In addition to CO2

Special Focus 475
In addition to CO2, Cl and BPG also bind better to deoxyhemoglobin than to
oxyhemoglobin, causing a shift in equilibrium in favor of O2 release. These various
effects are demonstrated by the shift in the oxygen saturation curves for Hb in the
presence of one or more of these substances (Figure 15.29). Note that the O2-
binding curve for Hb  BPG  CO2 fits that of whole blood very well.
2,3-Bisphosphoglycerate Is an Important Allosteric Effector
for Hemoglobin
The binding of 2,3-bisphosphoglycerate (BPG) to Hb promotes the release
of O2 (Figure 15.29). Erythrocytes (red blood cells) normally contain about 4.5
mM BPG, a concentration equivalent to that of tetrameric hemoglobin molecules.
Interestingly, this equivalence is maintained in the Hb-
BPG binding stoichiome-
try because the tetrameric Hb molecule has but one binding site for BPG. This
site is situated within the central cavity formed by the association of the four sub-
units. The strongly negative BPG molecule (Figure 15.30) is electrostatically bound
via interactions with the positively charged functional groups of each Lys 82, His
2, His 143, and the NH3
-terminal group of each -chain. These positively
charged residues are arranged to form an electrostatic pocket complementary to
the conformation and charge distribution of BPG (Figure 15.31). In effect, BPG
crosslinks the two -subunits. The ionic bonds between BPG and the two -chains
aid in stabilizing the conformation of Hb in its deoxy form, thereby favoring the
dissociation of oxygen. In oxyhemoglobin, this central cavity is too small for BPG
to fit. Or, to put it another way, the conformational changes in the Hb molecule
that accompany O2 binding perturb the BPG-binding site so that BPG can no
longer be accommodated. Thus, BPG and O2 are mutually exclusive allosteric ef-
fectors for Hb, even though their binding sites are physically distinct.
BPG Binding to Hb Has Important Physiological Significance
The importance of the BPG effect is evident in Figure 15.29. Hemoglobin stripped
of BPG is virtually saturated with O2 at a pO2 of only 20 torr, and it cannot release its
oxygen within tissues, where the pO2 is typically 40 torr. BPG shifts the oxygen satu-
ration curve of Hb to the right, making the Hb an O2 delivery system eminently
suited to the needs of the organism. BPG serves this vital function in humans, most
primates, and a number of other mammals. However, the hemoglobins of cattle,
sheep, goats, deer, and other animals have an intrinsically lower affinity for O2, and
these Hbs are relatively unaffected by BPG.
Fetal Hemoglobin Has a Higher Affinity for O2 Because
It Has a Lower Affinity for BPG
The fetus depends on its mother for an adequate supply of oxygen, but its circulatory
system is entirely independent. Gas exchange takes place across the placenta. Ideally
20
0
20 40 60
pO2, torr
100
80
60
40
Percent O2 saturation
Stripped Hb
Hb + CO2
Hb + BPG
Hb + BPG + CO2
Whole blood
FIGURE 15.29 Oxygen-binding curves of blood and of
hemoglobin in the absence and presence of CO2 and
BPG. From left to right: stripped Hb, Hb  CO2, Hb 
BPG, Hb  BPG  CO2, and whole blood.
HC OPO3
2–
C
O P
H2C OPO3
2–
O O–
O–
O–
O
C
H
H
C
H
C
O
O
O
P O
–O
–O
–
FIGURE 15.30 The structure, in ionic form, of BPG or 2,3-bisphosphoglycerate, an important allosteric effector
for hemoglobin.