MadSci Network: Biochemistry

Re: How is HCl produced in the stomach?

Date: Wed Oct 28 15:06:44 1998
Posted By: Michael Onken, MadSci Admin
Area of science: Biochemistry
ID: 904898050.Bc

First, there is a tremendous web site at Colorado State with a Java Applet demonstrating the production of gastric acid by pariental cells (click here), which explains the process better than I could. That aside, the process is really quite simple, so I'll try to explain it here.

The lining of the stomach is composed of two main epithelial cells which produce the gastric juices that digest our food. These are the Chief Cells, which excrete pepsin, trypsin, and a host of other enzymes, and the Parietal Cells, which excrete hydrochloric acid (HCl). Parietal cells accomplish this through a membrane protein called K+/H+ ATPase. This enzyme functions as a facilitated antiporter: that is, it swaps potassium ions (K+) outside the cell for protons (hydrogen ions, H+: these ions actually exist as hydronium ions, H3O +, in aqueous solutions, but most people still refer to protons for simplicity) inside the cell, so that the K+ is pumped in as the H+ is pumped out. Although this has no affect on the polarity of the membrane (one positive charge in for one out), it does result in a chemical gradient of each ion, such that energy is required to keep the pump working. This energy is supplied by the hydrolysis (breaking) of ATP to ADP and phosphate, catalyzed by the enzyme itself - hence K+/H+ ATPase. At the same time that H+ is being pumped out of the cell, Chloride ions (Cl- ) leak out of the cell, through special membrane chloride channels, producing a net flow of H+ Cl - out of the parietal cell and into the lumen of the stomach - since HCl dissociates completely in water, it is equivalent to add the H + and Cl- separately.

The problem with all this pumping is that eventually you end up with a parietal cell full of potassium but devoid of protons and chloride. The first problem, potassium, is solved by potassium channels that allow K+ to diffuse back out of the cell (this "short-circuit" helps in pumping protons into stomach by maintaining a continuous supply of K+ outside the cell). The second problem, protons, is solved by taking advantage of a common chemical reaction: carbon dioxide (CO 2) dissolved in water (H2 O) reacts to form carbonic acid (H2 CO3) - this is why soft drinks are acidic. Since all cells generate CO2 as a metabolic by- product, carbonic acid is a good source of protons, as it dissociates into H + and HCO3 - (bicarbonate). However, the formation of carbonic acid is a slow reaction in most cells, so parietal cells contain the enzyme carbonic anhydrase, which catalyses the formation of carbonic acid in the cell, greatly increasing the available protons. The third problem, chloride, is solved by exchanging bicarbonate ions in the cell for chloride ions in the blood through another channel, a Cl-/HCO3- exchanger that moves chloride ions into the cell while also alleviating the build-up of bicarbonate ions, as a result of cabonic anhydrase, by moving them out of the cell into the blood.

So to sum up: carbonic anhydrase catalyses the reaction between CO2 and H2O to produce H 2CO3, which dissociates into H+ and HCO3 -; the HCO3 - is exchanged for Cl- in the blood, and the excess Cl- diffuses into the stomach as the H+ is pumped into the stomach while circulating K+ and using ATP as an energy source. Again, it is worth seeing the whole process animated at: stomach/parietal.html

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