Researchers are studying the structure and function of hemoglobin. Arterial and venous blood samples are obtained from enrolled volunteers with no health problems. Red blood cells are isolated from whole blood by differential centrifugation, and the contents of the intact red blood cells are analyzed. It is found that the concentration of chloride is much lower in the red blood cells in the arterial sample compared to the venous sample. The activity of which of the following enzymes is most likely responsible for the observed finding?
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Hemoglobin is only found within red blood cells (RBCs), and it is responsible not only for O2 delivery to the tissues, but also for carrying CO2 from the tissues to the lungs. Hemoglobin carries CO2 in the form of carbaminohemoglobin, which is created as follows:
CO2 + Hb-NH3 = 2H+ + Hb-NH-CO2
However, only a small percentage of total blood CO2 is carried by hemoglobin. The majority of total blood CO2 is carried in the plasma as bicarbonate ion (HCO3−) via the following process:
The CO2 produced by tissue metabolism enters RBCs and is hydrated by the enzyme carbonic anhydrase to form carbonic acid (H2CO3).
H2CO3 then undergoes spontaneous conversion to HCO3− and H+.
The excess HCO3− is then transferred out of RBCs into the plasma via band 3 protein in exchange for chloride ions (Cl−) to maintain electrical neutrality. This exchange is known as "chloride shift" and is the principal cause of high RBC chloride content in venous blood.
(Choice A) Bisphosphoglycerate (BPG) mutase converts 1,3-BPG to 2,3-BPG. In RBCs, 2,3-BPG combines with hemoglobin to decrease its affinity for O2 and facilitate O2 unloading in the tissues.
(Choices C and E) Glucose-6-phosphate dehydrogenase is the first enzyme in the pentose phosphate pathway (produces NADPH) and pyruvate kinase catalyzes the final step of glycolysis (produces ATP). Deficiency of either glucose-6-phosphate dehydrogenase or pyruvate kinase typically leads to shortened RBC lifespan and episodic hemolysis triggered by oxidative stressors.
(Choice D) Na+/K+-ATPase is responsible for the maintenance of ionic concentration gradients across the plasma membrane in many cells in the body. This energy-requiring pump is electrogenic as it extrudes 3 sodium ions for every 2 potassium ions that enter the cell, which creates negative intracellular potential.
Educational objective:
The majority of CO2 produced in the tissues is transported to the lungs as bicarbonate ion (HCO3−). Within red blood cells (RBCs), the enzyme carbonic anhydrase forms HCO3− from CO2 and water. The excess HCO3− is then transferred out of RBCs into the plasma via exchange with chloride ions (Cl−). This exchange is known as "chloride shift" and is the principal cause of high RBC chloride content in venous blood.