474 Chapter 15 Enzyme RegulationExp

474 Chapter 15 Enzyme Regulation
Expressed another way, H is an antagonist of oxygen binding by Hb, and the satu-
ration curve of Hb for O2 is displaced to the right as acidity increases (Figure 15.28).
This phenomenon is called the Bohr effect, after its discoverer, the Danish physiol-
ogist Christian Bohr (the father of Niels Bohr, the atomic physicist). The effect has
important physiological significance because actively metabolizing tissues produce
acid, promoting O2 release where it is most needed. About two protons are taken
up by deoxyhemoglobin. The N-termini of the two -chains and the His 146
residues have been implicated as the major players in the Bohr effect. (The pKa of
a free amino terminus in a protein is about 8.0, but the pKa of a protein histidine
imidazole is around 6.5.) Neighboring carboxylate groups of Asp 94 residues help
stabilize the protonated state of the His 146 imidazoles that occur in deoxyhemo-
globin. However, when Hb binds O2, changes in the conformation of -chains upon
Hb oxygenation move the negative Asp function away, and dissociation of the
imidazole protons is favored.
CO2 Also Promotes the Dissociation of O2 from Hemoglobin
Carbon dioxide has an effect on O2 binding by Hb that is similar to that of H,
partly because it produces H when it dissolves in the blood:
The enzyme carbonic anhydrase promotes the hydration of CO2. Many of the protons
formed upon ionization of carbonic acid are picked up by Hb as O2 dissociates. The
bicarbonate ions are transported with the blood back to the lungs. When Hb be-
comes oxygenated again in the lungs, H is released and reacts with HCO3
 to re-
form H2CO3, from which CO2 is liberated. The CO2 is then exhaled as a gas.
In addition, some CO2 is directly transported by hemoglobin in the form of car-
bamate (ONHCOO). Free -amino groups of Hb react with CO2 reversibly:
This reaction is driven to the right in tissues by the high CO2 concentration; the
equilibrium shifts the other way in the lungs where [CO2] is low. Thus, carbamyla-
tion of the N-termini converts them to anionic functions, which then form salt links
with the cationic side chains of Arg 141 that stabilize the deoxy or T state of
hemoglobin.
RONH2  CO2 RO O NH COO H
CO2 H2O H2CO3 HCO3   H  carbonic anhydrase
carbonic acid bicarbonate
100
80
60
40
20
0
Percent saturation
0 20 40 60 80 100 120 140
pO2, torr
Myoglobin
Arterial
pO2
Venous
pO2
pH 7.6
pH 7.4
pH 7.2
pH 7.0
pH 6.8
FIGURE 15.28 The oxygen saturation curves for myoglo-
bin and for hemoglobin at five different pH values: 7.6,
7.4, 7.2, 7.0, and 6.8.