Carbon Dioxide Transport

Overview of Carbon Dioxide Transport

• Carbon dioxide ($CO_2$) is transported throughout the body through three primary mechanisms.

• The efficiency and method of transport are heavily dependent on solubility, partial pressure gradients, and specific biochemical reactions within red blood cells.

Dissolved Carbon Dioxide in Blood Plasma

• Approximately $7\%$ of the total carbon dioxide in the body is transported by being dissolved directly into the blood plasma.

• This process is based on the solubility of carbon dioxide in water/fluid.

• The movement of dissolved $CO_2$ follows a strict partial pressure gradient:

  • In the tissues: Carbon dioxide moves from the tissues into the plasma because the partial pressure of $CO_2$ is higher in the tissues.

  • In the lungs: Carbon dioxide moves out of the blood and into the alveolus because the partial pressure is lower in the alveolar sac.

Carbon Dioxide Attachment to Hemoglobin (Carbaminohemoglobin)

• Approximately $20\%$ of carbon dioxide is transported by attaching to the protein structure of hemoglobin.

• Hemoglobin Structure:

  • Hemoglobin consists of four subunits: two alpha ($\alpha$) subunits and two beta ($\beta$) subunits.

  • These are globular proteins connected together.

  • At the center of each subunit is a heme group containing an iron molecule ($Fe$) where oxygen ($O_2$) attaches.

• Binding Site for $CO_2$:

  • Carbon dioxide does not attach to the heme group or the iron molecule.

  • Instead, $CO_2$ attaches to the amino groups ($-NH_2$) of the specific amino acids that make up the protein sequences of the hemoglobin subunits.

• Non-Competitive Binding:

  • Because $CO_2$ binds to amino groups and $O_2$ binds to the iron in the heme group, carbon dioxide does not compete directly with oxygen for the same binding site.

Bicarbonate Ion Transport and the Chloride Shift

• The vast majority of carbon dioxide—approximately $73\%$ to $80\%$—is transported as the bicarbonate ion ($HCO_3^-$).

• Intracellular Reaction:

  • Carbon dioxide is lipid-soluble, allowing it to pass easily through the lipid bilayer of the red blood cell membrane.

  • Inside the red blood cell, carbon dioxide encounters water ($H_2O$).

• Enzymatic Catalysis:

  • The reaction between $CO_2$ and $H_2O$ is catalyzed by the enzyme carbonic anhydrase.

  • This reaction occurs very rapidly to form carbonic acid ($H_2CO_3$):     $CO_2 + H_2O \rightleftharpoons H_2CO_3$

• Dissociation of Carbonic Acid:

  • Carbonic acid almost immediately dissociates into a bicarbonate ion ($HCO_3^-$) and a hydrogen ion ($H^+$):     $H_2CO_3 \rightleftharpoons HCO_3^- + H^+$

• The Buffering Capacity of Hemoglobin:

  • The free hydrogen ions ($H^+$) attach to the amino groups of hemoglobin.

  • This acts as a buffer to maintain pH and simultaneously destabilizes the bond between hemoglobin and oxygen, facilitating the delivery of oxygen to tissues that are producing high levels of $CO_2$.

• The Chloride Shift Mechanism:

  • The cell must maintain electrical neutrality. When the negatively charged bicarbonate ion ($HCO_3^-$) leaves the red blood cell to enter the plasma, the cell must compensate.

  • To maintain this balance, a chloride ion ($Cl^-$) is moved into the cell as the bicarbonate ion moves out.

  • This exchange is facilitated by an antiport protein.

  • This mechanism is highly efficient and is reused in other parts of the body, such as in the enterocytes of the stomach.

Biological Efficiency and the "Alkaline Tide"

• Humans have approximately $22,000$ to $25,000$ genes that code for proteins, necessitating the reuse of specific protein mechanisms like the chloride shift.

• In the Stomach:

  • The same antiport protein is used to remove bicarbonate from stomach cells into the blood while moving chloride into the cell (which is then secreted into the stomach to form hydrochloric acid, $HCl$).

  • This process results in the "alkaline tide," where blood draining from the stomach becomes more basic due to the high concentration of dissolved $HCO_3^-$.

• In the Blood:

  • The bicarbonate ion in the plasma serves as a critical buffer to help maintain a neutral blood pH.

Reversal of the Process in the Lungs

• To respire (exhale) the carbon dioxide, the entire chemical process must be reversed once the red blood cells reach the pulmonary capillaries:

  1. Chloride Exit: A chloride ion ($Cl^-$) is kicked out of the red blood cell.

  2. Bicarbonate Entry: The bicarbonate ion ($HCO_3^-$) moves from the plasma back into the red blood cell.

  3. Recombination: The bicarbonate ion recombines with a hydrogen ion ($H^+$) to reform carbonic acid ($H_2CO_3$).

  4. Conversion to Gas: Carbonic anhydrase catalyzes the conversion of carbonic acid back into water and carbon dioxide:     $H_2CO_3 \rightarrow H_2O + CO_2$

• Diffusion into Alveoli:

  • Because the partial pressure of carbon dioxide ($P_{CO_2}$) is lower in the alveolus than in the extracellular fluid around the tissues/blood, the reaction favors the production of $CO_2$ gas.

  • The dissolved $CO_2$ moves through the lipid bilayer of the capillary and alveolar membranes into the alveolar sac to be breathed out.