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How is it that the CL-/HCO3- exchanger operates in one direction in tissues and in the...

How is it that the CL-/HCO3- exchanger operates in one direction in tissues and in the opposite direction in the lungs?

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Expert Solution

ANS: Transmembrane anion exchange is essential to an important function of the erythrocyte the transport of waste carbon dioxide (CO2), which is generated in peripheral tissues, to the lungs for excretion by respiratory exhalation .Waste CO2 released from cells into the capillary blood diffuses across the erythrocyte membrane. In its gaseous form, CO2 dissolves poorly in aqueous solutions, such as the cytosol or blood plasma, but the potent enzyme carbonic anhydrase inside the erythrocyte converts CO2 to the water-soluble bicarbonate (HCO3−) anion:

The release of oxygen from hemoglobin into the peripheral capillaries induces a conformational change in the globin polypeptide that enables a histidine side chain to bind the proton produced by the carbonic anhydrase reaction. Meanwhile, the HCO3− formed by carbonic anhydrase is transported out of the erythrocyte in exchange for an entering Cl− via Anion Exchanger 1 protein If anion exchange did not occur, HCO3− would accumulate inside the erythrocyte to toxic levels during periods of exercise, when much CO2 is generated. About 80 percent of the CO2 in blood is transported as HCO3− generated inside erythrocytes; anion exchange allows about two-thirds of this HCO3− to be transported by blood plasma external to the cells, increasing the amount of CO2 that can be transported from tissues to the lungs. Also, without anion exchange, the increased HCO3− concentration in the erythrocyte would cause the cytosol to become alkaline. The exchange of HCO3− for Cl− causes the cytosolic pH to remain near neutrality.

The overall direction of this anion-exchange process is reversed in the lungs. CO2 diffuses out of the erythrocyte and is eventually expelled in breathing. The lowered concentration of CO2 within the cytosol drives the carbonic anhydrase reaction, as written above, from right to left: HCO3− reacts to yield CO2 and OH−. At the same time, oxygen binding to hemoglobin causes a proton to be released from hemoglobin; the proton combines with the OH− to form H2O. The lowered intracellular HCO3− concentration causes HCO3− to enter the erythrocyte in exchange for Cl− .


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