Digestion requires a complex series of actions involving several specialized enzymes working in unison. Pepsin is one of these enzymes. Each enzyme can destroy a specific type of bond between amino acids, and pepsin specializes in destroying peptide bonds. By doing this, the enzymes can cooperatively break down proteins that the small intestine can then absorb. This provides nutrients and energy necessary for the body to operate. This is also the first of the enzymes to activate whenever food needs digesting.


Amino Acids

Without proper knowledge of the underlying mechanics and molecules, pepsin's role in digestion can seem complicated. Amino acids are special organic compounds that allow the body to perform many biological functions. Some allow the body to create collagen and others allow for the transportation of fats. Each amino acid belongs to a category: essential, conditionally essential, or nonessential. The body cannot produce essential amino acids, so we must obtain them through diet.

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Proteins and Peptides

Amino acids are essentially the building blocks of proteins and peptides, which consist of chains of amino acid residues. These residues are amino acid molecules that are capable of undergoing a fusion process with other molecules to make a single, large molecule. The difference between a protein and a peptide is a matter of size and variety. Proteins are large molecules and can contain over 50 types of amino acids. Peptides receive their name from the peptide bonds that hold the amino acids together in the chains. Pepsin can sever these bonds and break proteins down into peptides. Because of this ability, this enzyme is considered a protease.

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Pepsin is a type of protease that uses an aspartate carboxylic acid, such as an amino acid. Aspartic proteases, for instance, activate a water molecule and use it to sever peptide bonds, a process called hydrolysis. There are seven groups of proteases, and pepsin works alongside the serine proteases chymotrypsin and trypsin to perform digestion. Of these three proteases, pepsin is the first to activate and respond. It performs the initial breakdown in the stomach while chymotrypsin and trypsin activate in the duodenum and the small intestine, respectively.

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Peptide Bonds

Many types of bonds can hold molecules together. Two amino acids will move towards each other and prepare to undergo a reaction. The carboxyl group of one molecule approaches the amino group of the other molecule. The carboxyl group loses a hydrogen and an oxygen, and the amino group loses a hydrogen. This releases a full molecule of water (H2O), classifying it as a condensation reaction. The hydrolysis that cleaves these bonds is essentially the opposite reaction, adding water instead of removing it.

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A zymogen is an inactive substance that becomes an enzyme when another enzyme activates it through a chemical reaction. Once the enzyme is active, it can begin performing its duties. Pepsinogen is the zymogen of pepsin. When the body activates pepsin, it loses a number of its amino acids, exposing catalytic sites. These are the areas of an enzyme that can bind with molecules and cause chemical reactions.

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Activating Pepsinogen

Despite popular belief, the gastric acid of the stomach does not perform any digesting itself. However, it does play a key role in the digestion process. When the brain senses food, the hormone gastrin triggers two events: cells in the stomach lining secrete hydrochloric acid into the gastric acid, and chief cells in the stomach release pepsinogen. When the pepsinogen and the hydrochloric acid meet, they undergo a chemical reaction and generate pepsin. Studies show this reaction can occur outside the stomach as well, but it is much slower.

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The Requirements of Pepsin

For pepsin to be as active as possible, it requires temperatures around 98 to 107 degrees Fahrenheit. Additionally, it is most active in acidic environments of between pH 1.5 to 2. In environments of pH 6.5 or above, pepsin becomes inactive. Around pH 8, pepsin becomes permanently inactive. Because pepsin is so stable even at high pH levels, it can remain in environments such as the larynx following gastric reflux. Typically, the pepsin is inactive without the presence of the gastric acid. However, another reflux event would activate the pepsin and damage the surrounding tissue.

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Laryngopharyngeal Acid Reflux

The larynx or voice box is the organ in the throat that assists with breathing, speaking, and preventing food aspiration. Laryngopharyngeal acid reflux involves gastric reflux that flows into the larynx or the areas of the mouth and nose just above it. Experts sometimes call this extraesophageal reflux disease or EERD. Pepsin can exist in the larynx for an indefinite period, as the larynx is ph 6.8. Once a gastric reflux event occurs, the pepsin activates and begins to damage the surrounding tissue.

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Preventing Damage

Because pepsin is stable in many environments, it can pose a threat to itself if there are no other proteins present. The enzyme requires inhibition so that it does not immediately attempt to destroy itself. This is partially why it begins as pepsinogen. Additionally, it undergoes feedback inhibition, a phenomenon where the output of a process also inhibits the beginning of the process. In the case of pepsin, a product of protein digestion inhibits it and causes it to slow down.

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Commercial Applications

Pepsin’s ability to break down proteins makes it appealing for many commercial enterprises. For example, rennet is a set of enzymes that curdles milk, enabling efficient cheese production. The leather industry uses pepsin to remove hair and various other tissue from hides. In the 1800s, a company developed a laxative from pepsin. Modern scientists use pepsin to break antibodies into fragments for closer and more detailed study.

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