Enteropeptidase

Enteropeptidase, also known as enterokinase, is a digestive system serine protease that initiates the activation of pancreatic digestive enzymes in the small intestine. It is produced by the mucosal cells of the duodenum as an inactive zymogen and is activated at the brush border, in part by trypsin.

Functionally, enteropeptidase cleaves the N-terminal activation peptide of trypsinogen at the sequence Asp-Asp-Asp-Asp-Lys (the DDDDK motif), releasing active trypsin. The generated trypsin then activates other pancreatic proenzymes, such as chymotrypsinogen, proelastase, and procarboxypeptidases, amplifying the proteolytic cascade essential for protein digestion.

Biochemically, enteropeptidase is a serine protease of the S1 family. It is typically composed of distinct subunits that become a functional enzyme after proteolytic processing and interacts with standard serine protease inhibitors.

Clinical significance is limited but notable. Congenital enteropeptidase deficiency is rare and results in impaired activation of pancreatic enzymes, potentially causing malabsorption and steatorrhea. Diagnosis relies on enzymatic testing, and management may include pancreatic enzyme replacement and dietary adjustments.

In biotechnology, enteropeptidase is widely used to cleave recombinant fusion proteins at the DDDDK recognition site, allowing release of the target protein from affinity tags. Commercial preparations are derived from porcine intestine or produced recombinantly; conditions are chosen to minimize nonspecific cleavage of the protein of interest.