enterokinasa

Enteropeptidase, also known as enterokinase or enteropeptidase, is a serine protease enzyme located on the brush border of the mucosal cells lining the upper small intestine, primarily the duodenum and proximal jejunum. It functions as the first step in the pancreatic digestive enzyme activation cascade.

Its main role is to activate the pancreatic zymogen trypsinogen by proteolytically cleaving its activation peptide after the lysine residue in the sequence Asp-Asp-Asp-Asp-Lys (the DDDDK recognition site). This cleavage releases active trypsin, which then autocatalytically amplifies its own production and activates other pancreatic zymogens, including chymotrypsinogen, proelastase, and procarboxypeptidases, enabling protein and fat digestion.

In mammals, enteropeptidase is produced as a zymogen and is typically a membrane-associated glycoprotein on the apical surface of enterocytes. It generally exists as a two-chain enzyme (heavy and light chains) held together by disulfide bonds, formed by proteolytic processing of a single precursor.

In biotechnology, recombinant enterokinase is employed to cleave proteins at the DDDDK site to remove affinity tags from fusion proteins, enabling tagless purification. While highly specific for the DDDDK sequence, the enzyme can cleave at similar Lys-containing sites under certain conditions, so experimental design accounts for potential off-target cleavage.

Deficiency or dysfunction of enteropeptidase is rare but can contribute to impaired digestion due to inadequate activation of pancreatic proteases, highlighting its essential role in intestinal protein digestion.