Trypsin and related luminal serine proteases

Trypsin and related luminal serine proteases, such as chymotrypsin and elastase, are essential digestive enzymes synthesized as inactive zymogens in the pancreas and activated within the intestinal lumen (StatPearls, 2023). These enzymes primarily function to hydrolyze dietary proteins into smaller peptides and amino acids, but they also serve as potent signaling molecules by activating Protease-Activated Receptors (PARs), specifically PAR2, on the intestinal epithelium (PubMed, PMID: 28435139). In pathological states like pancreatitis, the premature intrapancreatic activation of trypsin leads to autodigestion and severe inflammation (NIH, 2022). In the context of gastrointestinal disorders like irritable bowel syndrome (IBS), elevated levels of these proteases in the lumen are associated with impaired barrier function and visceral pain (PubMed, PMID: 31513884). Additionally, these proteases play a critical role in infectious diseases, as many viruses utilize host serine proteases to prime their spike or envelope proteins for cell entry (Nature, 2020). Pharmacological inhibitors such as camostat mesylate and nafamostat are used to target these enzymes to treat pancreatitis and are being investigated for their potential to block viral transmission (DrugBank, DB13729).

Other names

Pancreatic serine proteasesDigestive serine proteasesGastrointestinal serine proteasesTrypsin-like proteasesPRSS1PRSS2PRSS3Cationic trypsinogenAnionic trypsinogenMesotrypsin

Competitive or non-competitive inhibition of the serine protease catalytic triad (Ser-His-Asp), preventing the cleavage of peptide bonds in target proteins and zymogens.