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Bicarbonate Buffering System

The bicarbonate buffering system is an acid-base homeostatic mechanism involving the balance of carbonic acid (H₂CO₃), bicarbonate ion (HCO₃^-), and carbon dioxide (CO₂) in order to maintain pH in the blood and duodenum, among other tissues, to support proper metabolic function. Catalyzed by carbonic anhydrase, carbon dioxide reacts with water to form carbonic acid, which in turn rapidly dissociates to form a hydrogen ion (present in solution as hydronium ion) and a bicarbonate ion as shown in the following reaction:

${\rm {2CO_{2}+H_{2}O\rightleftarrows H_{2}CO_{3}\rightleftarrows HCO_{3}^{-}+H_{3}O^{+}}}$

As with any buffer system, the pH is balanced by the presence of both weak acid (i.e. H₂CO₃) and conjugate base (i.e. HCO₃^-) so that any excess acid or base introduced to the system is neutralized.

Physiological Mechanism

In the blood, carbon dioxide generated from cellular respiration is converted to bicarbonate ion so that it may be transported to the lungs, where it is converted back into carbon dioxide and released during exhalation. The bicarbonate buffering system plays a vital role in other tissues as well. In the human duodenum, the bicarbonate buffering system serves to both neutralize gastric acid and stabilize the intracellular pH of duodenal epithelial cells via the secretion of bicarbonate ion.

Failure of this system to function properly results in acid-base imbalance such as acidemia (pH<7.35) and alkalemia (pH>7.45) in the blood, or ulcers in the duodenum, as seen in H. pylori infection.[3]

Regulation of the Bicarbonate Buffer

The maintenance of steady state concentrations, approximately 20:1 bicarbonate to carbonic acid, of each species are maintained so as to maximize the buffer capacity of the system; this homeostasis is mediated by through several enzymatic regulators; carbonic anhydrase, among the most contributing of these regulators located in the plasma and in duodenal epithelial cell, facilitates the hydration and dehydration reactions between bicarbonate ion and carbon dioxide in response to the local concentrations of each.[2] Furthermore, in the blood of most animals, the bicarbonate buffering system is coupled to the lungs via respiratory compensation, the process by which the rate of breathing changes to compensate for changes in the blood concentration of CO₂. By Le Chȃtlier’s Principle, the release of CO₂ from the lungs pushes the reaction above to the left, causing carbonic anhydrase to form CO₂ until all excess acid is removed. Bicarbonate concentration is also further regulated by renal compensation, the process by which the kidneys regulate the concentration of bicarbonate ion by filtering out excess or retaining it when in low concentrations.

Derivation of Modified Henderson Equation

The Henderson Equation, which is derived from the Law of Mass Action, can be modified with respect to the bicarbonate buffering system to yield a simpler equation that provides a quick approximation of the HCO₃^- concentration without the need to calculate logarithms:

${\rm {K_{a,H_{2}CO_{3}}={\frac {[HCO_{3}^{-}][H_{3}O^{+}]}{[H_{2}CO_{3}]}}}}$

Rearranging the equation and applying the Henry’s Law solubility constant for CO₂ in plasma in lieu of the carbonic acid concentration yields[2]:

${\rm {[H^{+}]={\frac {K'\cdot 0.03P_{CO_{2}}}{[HCO_{3}^{-}]}}}}$

Where K’ is the dissociation constant from the pKa of carbonic acid, 6.1, which is equal to 800nmol/L (since 10^-6.1≈ 8.00X10^-07). By multiplying K’ and 0.03 and rearranging with respect to HCO₃^-, the equation is simplified to[5]:

${\rm {[HCO_{3}^{-}]=24{\frac {P_{CO_{2}}}{[H^{+}]}}}}$

Amino Acid

[Insert acid] is a(n) [ essential/nonessential ] amino acid used as monomers in the biosynthesis of proteins. [insert acid] is considered a [polar/nonpolar] amino acid due to [insert functional group]. It is also considered a [neutral/acidic/basic] acid, due to its [high/low] pKa. [Insert sentence regarding the effect of these characteristics in motifs, other functions].

Histidine

Physiologically Relevant Structure of L-Histidine in ACS Format

Histidine (abbreviated as His or H; encoded by the codons CAU and CAC) is an ɑ-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –⁺NH3 form under biological conditions), an α-carboxylic acid group (which is in the deprotonated –COO^- form under biological conditions), and a side chain imidazole, classifying it as a positively charged (at physiological pH), aromatic amino acid. It is essential in humans, meaning the body cannot synthesize it and thus it must be obtained from the diet.

"Histidine was first isolated by German physician Albrecht Kossel in 1896." It is also a precursor to histamine, a vital inflammatory agent in immune responses.

Tryptophan

Tryptophan (abbreviated as Trp or W; encoded by the codon UGG) is an ɑ-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –⁺NH3 form under biological conditions), an α-carboxylic acid group (which is in the deprotonated –COO^- form under biological conditions), and a side chain indole, classifying it as a non-polar, aromatic amino acid. It is essential in humans, meaning the body cannot synthesize it and thus it must be obtained from the diet.

Tryptophan is also a precursor to neurotransmitters serotonin and melatonin.

Pyrrolysine

Physiologically Relevant Structure of L-Pyrrolysine in ACS Format

Pyrrolysine (abbreviated as Pyl or O; encoded by the 'amber' stop codon UAG) is an ɑ-amino acid that is used in the biosynthesis of proteins in some methanogenic archaea and bacterium. It contains an α-amino group (which is in the protonated –⁺NH3 form under biological conditions), an α-carboxylic acid group (which is in the deprotonated –COO^- form under biological conditions), and a side chain methyl-pyrroline, classifying it as a positively charged (at physiological pH), aromatic amino acid. It is not present in humans so it is not classified as an essential amino acid.

My Thoughts

Some things I'm thinking about approaching for the the Bicarbonate buffering system:

Maybe I would like to elucidate upon the mechanisms, consequences, etc. of bicarbonate buffering in the small intestines. Maybe I should introduce by explaining the range of the buffer system and how it can apply to systems other than the blood. The bicarbonate buffering system also exists in the intestines.

Another great reference that goes into how bicarbonate ion protects the intestines. Who knew!

The practical use of bicarbonate in cell culture media would bring a practical aspect to the article regarding research and laboratory procedures, etc. Practical use of bicarbonate buffer in media? Krebs-Ringer buffer solution.

For relating the HH equation to the blood buffering system,

This reference is really explicit in its explanation of the movement of HCO3- ions and the specific transport proteins involved in bicarbonate ion movement. I could use this to elaborate on how bicarbonate moves and maybe how disfunction could relate to disease.