Introduction

Hemoglobin (Hb), beyond transporting oxygen, plays a significant role in maintaining acid-base balance in the blood through its buffering capacity. This capacity is mainly due to certain amino acid residues within hemoglobin, particularly from histidine, which contains imidazole groups essential for proton exchange. This article reviews the biochemical basis of Hb buffering capacity and identifies the correct statements about its function.

Analysis of the Proposed Statements

A. Hb buffering capacity is due to a large number of histidine residues.

• True.
  Hemoglobin contains approximately 38 histidine residues per molecule, which have imidazole side chains with a pKa near physiological pH (~6.8). This allows them to accept or donate protons, effectively buffering changes in hydrogen ion concentration in the blood.

B. Imidazole groups of Hb dissociate less than those of oxyhemoglobin (HbO2).

• True.
  The imidazole groups in deoxygenated hemoglobin (Hb) are more basic and better at accepting protons than those in oxyhemoglobin (HbO2). Hence, deoxygenated Hb has a greater buffering capacity, which relates to the Haldane effect — deoxygenated Hb binds more H+ ions facilitating CO2 transport.

C. Hb buffering capacity is due to a large number of threonine residues.

• False.
  Threonine, an amino acid in proteins, does not significantly contribute to Hb’s buffering capacity. The primary contributors are the histidine residues and their imidazole groups.

D. Hb is a strong acid.

• False.
  Hemoglobin is not a strong acid; it is a protein with multiple buffering groups that can both accept and donate protons. Its buffering effect arises from its weakly basic imidazole groups, not from being an acid.

Summary Table

Conclusion

The combination of correct statements is:

(1) A and B

Physiological Role of Hemoglobin Buffering

• Hb buffers hydrogen ions resulting from CO2 hydration in red blood cells, limiting blood pH fluctuations.

• Deoxygenated Hb’s greater proton affinity supports CO2 transport through carbamate formation and enhanced acid buffering.

• This buffering buffering facilitates homeostasis during metabolic and respiratory changes.

Additional Insights

The Haldane effect exemplifies the dual role of Hb in gas transport and acid-base balance. Understanding this biochemical property is critical in clinical contexts involving respiratory or metabolic acidosis.