Pepsin can lie dormant in your throat and wake up with the next reflux
Your stomach's main protein-cutting enzyme only works in strong acid, yet it survives milder conditions without being destroyed. Carried up into the throat by reflux, pepsin sits idle at near-neutral pH, then springs back to life when more acid arrives, which helps explain why reflux can injure the larynx.
Theodor Schwann identified pepsin in 1836, making it one of the first enzymes known, and named it from the Greek for digestion. In 1928 John Northrop crystallised it using dialysis, filtration and cooling, again among the first enzymes to be handled that way. It belongs to the aspartic proteases, which use an aspartate in their active site, and it is one of three major enzymes in human digestion that snip proteins in the middle, alongside trypsin and chymotrypsin.
The stomach does not store it ready to use. Chief cells in the stomach wall release an inactive precursor, pepsinogen, which carries an extra 44 amino acids. When food arrives, the hormone gastrin and the vagus nerve trigger both pepsinogen and hydrochloric acid. The acid makes pepsinogen unfold and cut off its own extra segment, and each new pepsin molecule then trims more precursors, a self-accelerating chain. The enzyme works best between pH 1.5 and 2.5, and its concentration in the human stomach reaches 0.5 to 1 mg/mL. It is not fussy: it can cleave up to 20% of the protein bonds it meets, favouring sites next to bulky water-shy amino acids such as phenylalanine.
Above pH 6.5 pepsin goes quiet, but it is only permanently wrecked at pH 8. That gap matters in laryngopharyngeal reflux. The throat averages about pH 6.8, where pepsin lingers inactive, ready to be revived by the next acid splash. Cells lining the airway can even absorb it at neutral pH and store it in acidic pockets for up to 24 hours, which shifts gene activity toward inflammation. Because pepsin should not normally be in the airway, finding it there is treated as a sensitive marker, and a saliva test called Peptest now checks for it.
Outside the body, commercial pepsin comes from the lining of pig stomachs. It is part of the rennet that curdles milk for cheese, helps turn cereals into instant porridge, strips hair from hides for leather, and frees silver from old photographic film by digesting the gelatin. It was once added to Beeman's chewing gum, and it gave Pepsodent toothpaste its name.
Source: Pepsin
