Principles of Biochemistry, Volume 3 - A. Lehninger 1985

Selected Aspects of Human Biochemistry
Digestion, Nutrient Transport, and Metabolic Interrelationships
Erythrocytes also transport CO₂

Carbon dioxide produced in Tissues is also transported by the Blood to the Lungs, from where it is eliminated via exhaled air. The carbon dioxide content in venous blood flowing away from tissues is approximately 60 mL of gaseous CO₂ per 100 mL of blood, whereas arterial blood leaving the lungs contains approximately 50 mL of CO₂ per 100 mL of blood. About two-thirds of the total blood CO₂ resides in the plasma and about one-third in the erythrocytes. However, during The transport of CO₂ from tissues to the lungs, nearly all blood CO₂ must pass through the erythrocytes (entering and exiting them). Both in plasma and in erythrocytes, CO₂ exists in two forms: as a dissolved gas and as bicarbonate (HCO^-₃). Because dissolved CO₂ undergoes reversible Hydration to form carbonic acid (Н₂СO₃), the mixture of Н₂СO₃ and НС^-O₃ in the blood forms a buffer system (Section 4.11), where Н₂СO₃ acts as a proton donor and the НСO^-₃ ion as its acceptor. The Н₂СO₃ – НСO^-₃ system serves as the primary buffer system of Blood Plasma.

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Fig. 24-22. Coordinated transport of oxygen and CO₂ by erythrocytes. A. In the lungs, the Oxygenation of Hemoglobin results in the release of H⁺ ions, which then combine with HCO₃ ions to form Н₂СO₃. Under the action of Carbonic anhydrase, H₂CO₃ undergoes dehydration, producing dissolved CO₂, which diffuses into the blood plasma and from there into the air spaces of the lungs to be exhaled. B. The uptake of dissolved CO₂ by erythrocytes in peripheral tissues requires the participation of carbonic anhydrase, which catalyzes the hydration of CO₂ to form Н₂СO₃; subsequently, Н₂СO₃ loses an Н⁺ ion and is converted into НСО^-₃. The H⁺ ions released in the process shift the equilibrium of the hemoglobin-oxygen reaction toward the release of oxygen and its delivery to the tissue. Because O₂ and CO₂ are lipid-soluble, they readily cross Cell membranes without The Need for membrane transport systems. However, the exchange between Cl^- and НСО^-₃ ions across The erythrocyte membrane occurs only via systems mediating anion transport.

The transport of CO₂ from tissues to the lungs consists of the following steps (Fig. 24-22). Dissolved CO₂, produced as an oxidation product in The Citric Acid Cycle as well as in other processes involving enzymatic decarboxylation, diffuses from the tissues into the blood plasma and further into the erythrocytes. Within the erythrocytes, CO₂ is hydrated in a reversible reaction to form free carbonic acid:

CO₂ + Н₂O ⇄ Н₂СО₃

In the absence of a catalyst, this reaction proceeds relatively slowly, and The formation of carbonic acid lags behind The production of CO₂ in respiring tissues. However, erythrocytes contain carbonic anhydrase—an exceptionally active enzyme that dramatically accelerates this reaction. As Н₂СO₃ is formed, it immediately ionizes to yield a bicarbonate ion:

Н₂СO₃ ⇄ Н⁺ + НСО^-₃

Fig. 24-23. Alveoli, or air sacs, of the lungs (A) provide a large surface area through which O₂ and CO₂ exchange occurs between alveolar air and blood capillaries. B. Electron micrograph showing alveoli and blood capillaries.

The HCO₃ ion thus formed exits the erythrocytes into the plasma in exchange for a chloride ion (Cl^-). As for the H⁺ ions appearing in erythrocytes from The ionization of carbonic acid (Н₂СO₃), they facilitate the release of oxygen from oxyhemoglobin According to the aforementioned reaction running in reverse:

Н⁺ + НbO₂ ⇄ ННb⁺ + O₂

Thus, the accumulation of H⁺ ions driven by The entry of CO₂ into erythrocytes and its conversion into HCO^-₃ facilitates oxygen delivery by the blood as it passes through peripheral tissues.

In the carbon dioxide-rich venous blood returning to the lungs, the same cycle proceeds in reverse. The binding of oxygen by hemoglobin in the pulmonary capillaries leads to the release of H⁺ ions:

ННb⁺ + O₂ ⇄ Н⁺ + НbO₂

The accumulation of H⁺, in turn, promotes the formation of carbonic acid from HCO^-₃ within the erythrocytes:

H⁺ + HCO^-₃ ⇄ H₂CO₃

Next, in the presence of carbonic anhydrase, carbonic acid undergoes dehydration to yield dissolved CO₂:

Н₂СО₃⇄ H₂O + CO₂

Dissolved CO₂ leaves the erythrocytes, enters the blood plasma, passes through the capillary walls, and is eliminated through the vast surface area of the lungs into the air space (Fig. 24-23). Overall, Oxygen transport and CO₂ transport mutually enhance each other, owing to The properties of hemoglobin, which is exquisitely adapted to perform these specialized transport Functions.