Hemoglobin Also Transports H and CO2

In addition to carrying nearly all the oxygen required by cells from the lungs to the tissues, hemoglobin carries two end products of cellular respiration—H+ and CO2— from the tissues to the lungs and the kidneys, where they are excreted. The CO2, produced by oxidation of organic fuels in mitochondria, is hydrated to form bicarbonate:

This reaction is catalyzed by carbonic anhydrase, an enzyme particularly abundant in erythrocytes. Carbon dioxide is not very soluble in aqueous solution, and bubbles of CO2 would form in the tissues and blood if it were not converted to bicarbonate. As you can see from the equation, the hydration of CO2 results in an increase in the H+ concentration (a decrease in pH) in the tissues. The binding of oxygen by hemoglobin is profoundly influenced by pH and CO2 concentration, so the interconversion of CO2 and bicarbonate is of great importance to the regulation of oxygen binding and release in the blood.

Hemoglobin transports about 40% of the total H+ and 15% to 20% of the CO2 formed in the tissues to the lungs and the kidneys. (The remainder of the H+ is absorbed by the plasma's bicarbonate buffer; the remainder of the CO2 is transported as dissolved HCO3 and CO2.) The binding of H+ and CO2 is inversely related to the binding of oxygen. At the relatively low pH and high CO2 concentration of peripheral tissues, the affinity of hemoglobin for oxygen decreases as H+ and CO2 are bound, and O2 is released to the tissues. Conversely, in the capillaries of the lung, as CO2 is excreted and the blood pH consequently rises, the affinity of hemoglobin for oxygen increases and the protein binds more O2 for transport to the peripheral tissues. This effect of pH and CO2 concentration on the binding and release of oxygen by hemoglobin is called the Bohr effect, after Christian Bohr, the Danish physiologist (and father of physicist Niels Bohr) who discovered it in 1904.

The binding equilibrium for hemoglobin and one molecule of oxygen can be designated by the reaction

HbO2

but this is not a complete statement. To account for the effect of H+ concentration on this binding equilibrium, we rewrite the reaction as

where HHb+ denotes a protonated form of hemoglobin. This equation tells us that the O2-saturation curve of hemoglobin is influenced by the H+ concentration (Fig. 5-16). Both O2 and H+ are bound by hemoglobin, but with inverse affinity. When the oxygen concentration is high, as in the lungs, hemoglobin binds O2 and releases protons. When the oxygen concentration is low, as in the peripheral tissues, H+ is bound and O2 is released.

Oxygen and H+ are not bound at the same sites in hemoglobin. Oxygen binds to the iron atoms of the hemes, whereas H+ binds to any of several amino acid residues in the protein. A major contribution to the Bohr effect is made by His146 (His HC3) of the 3 subunits. When protonated, this residue forms one of the ion pairs—to Asp94 (Asp FG1)—that helps stabilize deoxy-hemoglobin in the T state (Fig. 5-9). The ion pair stabilizes the protonated form of His HC3, giving this residue an abnormally high pKa in the T state. The pKa falls to its normal value of 6.0 in the R state because the ion pair cannot form, and this residue is largely unpro-

FIGURE 5-16 Effect of pH on the binding of oxygen to hemoglobin.

The pH of blood is 7.6 in the lungs and 7.2 in the tissues. Experimental measurements on hemoglobin binding are often performed at pH 7.4.

FIGURE 5-16 Effect of pH on the binding of oxygen to hemoglobin.

The pH of blood is 7.6 in the lungs and 7.2 in the tissues. Experimental measurements on hemoglobin binding are often performed at pH 7.4.

tonated in oxyhemoglobin at pH 7.6, the blood pH in the lungs. As the concentration of H+ rises, protonation of His HC3 promotes release of oxygen by favoring a transition to the T state. Protonation of the amino-terminal residues of the a subunits, certain other His residues, and perhaps other groups has a similar effect.

Thus we see that the four polypeptide chains of hemoglobin communicate with each other about not only O2 binding to their heme groups but also H+ binding to specific amino acid residues. And there is still more to the story. Hemoglobin also binds CO2, again in a manner inversely related to the binding of oxygen. Carbon dioxide binds as a carbamate group to the a-amino group at the amino-terminal end of each globin chain, forming carbaminohemoglobin:

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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