Hemoglobin Buffering: The Haldane Effect
One consequence of CO2 loading in the tissue capillary is the formation of hydrogen ions from CO2 hydration and carbamino group formation. Hemoglobin, and to a lesser extent plasma proteins, are capable of buffering many of the H+ produced as shown above. This buffering of H+ minimizes the blood pH change as it traverses the tissue capillaries. The peptide chains of Hb contain numerous amino and carboxyl groups (see top figure). The carboxyl groups of Hb are capable of binding, and hence buffering, many of the H+ formed as a result of CO2 transport. Over the normal physiological pH range, much of the buffering of H+ by Hb is performed by the imidazole group of the amino acid histidine, present in the globulin chain (see bottom figure). The imidazole group of histidine, like some other buffering groups, is closely associated with the iron atom of the heme portion of Hb. As O2 is released from the iron atom of Hb during transit through the tissue capillary, the electron structure of the Hb peptide chain is altered and groups like imidazole become more capable of binding H+. In other words, when Hb loses O2, it becomes a stronger base or weaker acid, making more sites available to buffer H+. The complete deoxygenation of 1 mM HbO2 to yield 1 mM O2 can result in the neutralization or buffering of 0.7 mM of H+. This ability of Hb to neutralize (buffer) more H+, as it releases oxygen is termed the Haldane effect. The Haldane effect is an important mechanism for facilitating the transport of CO2 by minimizing changes in free H+ or blood pH.