Pepsin is a key ingredient for a healthy digestive process. Its effectiveness in breaking down food in the stomach relies on a precise system of environmental controls preserving optimal pH levels. Barring certain medical conditions, this system needs no external intervention to stay on track. Over-the-counter remedies for self-diagnosed digestive problems generally do more harm than good.
History
Human pepsin A was the first enzyme to be discovered. Soon after its discovery in 1836, pepsin was shown to break down proteins. Its name relates to this function, deriving from the Greek word pepsis, "to digest."
Closest Ortholog
Orthologs are proteins found in two or more species that share a common ancestor. A number of orthologs to human pepsin A have been discovered in non-human species -- not just mammals, but also frogs, chickens, some bacteria and stable fly larvae. The nearest ortholog to human pepsin A, as determined by analyzing its amino acid sequences, is pig pepsin A.
Function
Pepsin breaks down proteins into polypeptides inside the stomach. These polypeptides will break down further into amino acids, dipeptides and tripeptides inside the small intestine.
Pepsin requires an acidic pH, ideally 2, in order to break down proteins. The low pH environment denatures the proteins, changing their shape and exposing the peptide bonds for pepsin to break.
Activation
Pepsin is secreted in an inactive form; otherwise, it would digest the very cells that synthesize it. The inactive form, pepsinogen, needs a low pH environment in order to convert to pepsin. Once pepsinogen reaches the stomach, where hydrochloric acid keeps the pH in the 1 to 3 range, it not only becomes pepsin but also triggers the formation of more pepsin.
Feedback Loop
Pepsin and hydrochloric acid are components of gastric juice. When you smell or taste food, that's the first trigger for the production of gastric juice. When you swallow food, it dilutes the hydrochloric acid, which slightly raises the pH of the stomach environment. This triggers the release of gastrin into the bloodstream, which in turn stimulates further gastric juice production. As your stomach empties of food, the pH drops, eventually reaching a level low enough to halt gastrin secretion.
This negative feedback loop is normally all your body needs to regulate the pH of your stomach contents. Over-the-counter antacids can exacerbate the symptoms they're supposed to counter. Raising the stomach pH hampers pepsin's effectiveness, increasing indigestion rather than alleviating it. Taking antacids can cause more acid production as the stomach attempts to maintain its acidic, pro-digestion environment.
