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Bicarbonate Buffering System

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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:

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

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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.[1]

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

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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

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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:

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

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]:

Amino Acid

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[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

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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."[2] It is also a precursor to histamine, a vital inflammatory agent in immune responses.

Tryptophan

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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

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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

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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.[1]

Another great reference that goes into how bicarbonate ion protects the intestines. Who knew! [3]

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.[4]

For relating the HH equation to the blood buffering system, [5]

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.[6]

References

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  1. ^ a b Krieg, Brian J.; Taghavi, Seyed Mohammad; Amidon, Gordon L.; Amidon, Gordon E. (11 September 2014). "In Vivo Predictive Dissolution: Transport Analysis of the CO2 , Bicarbonate In Vivo Buffer System". Journal of Pharmaceutical Sciences. 103 (11): 3473–3490. doi:10.1002/jps.24108. Retrieved 20 October 2015.
  2. ^ "Histidine". {{cite journal}}: Cite journal requires |journal= (help)
  3. ^ KAUNITZ, J. D.; AKIBA, Y. (5 January 2007). "Review article: duodenal bicarbonate - mucosal protection, luminal chemosensing and acid-base balance". Alimentary Pharmacology & Therapeutics. 24: 169–176. doi:10.1111/j.1365-2036.2006.00041.x.
  4. ^ Zander-Fox, Deirde; Lane, Michelle (25 June 2015). "Media Composition: Energy Sources and Metabolism". In Smith, Gary D.; Swain, Jason E.; Pool, Thomas B. (eds.). Embryo Culture. Humana Press. pp. 81–96. ISBN 978-1-61779-971-6. Retrieved 20 October 2015.
  5. ^ Wang, John Bullock, Joseph Boyle III, Michael B. (2001). Physiology (4th ed. ed.). Philadelphia, PA: Lippincott Williams & Wilkins. pp. 447–449. ISBN 9780683306033. {{cite book}}: |access-date= requires |url= (help); |edition= has extra text (help)CS1 maint: multiple names: authors list (link)
  6. ^ Cordat, Emmanuelle; Casey, Joseph R. (15 January 2009). "Bicarbonate transport in cell physiology and disease". Biochemical Journal. 417 (2): 423–439. doi:10.1042/BJ20081634. {{cite journal}}: no-break space character in |first2= at position 7 (help)