[Frontiers in Bioscience E1, 242-249, June 1, 2009]

Enteropeptidase, a type II transmembrane serine protease

X. Long Zheng1, Yasunori Kitamoto2, J. Evan Sadler3

1Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia and The University of Pennsylvania School of Medicine, Philadelphia, PA 19104, 2Department of Internal Medicine, Sendai Shakai-Hoken Hospital, 3-16-1 tsutsumi-machi, Aoba-ku Sendai 9818501, Japan, 3Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110


3. Gene and protein structure
3.1. Proenteropeptidase gene
3.2. Proenteropeptidase domain structure
4. Biosynthesis and trafficking
4.1. Localization of enteropeptidase
4.2. Intracellular trafficking
5. Zymogen activation
6. Substrate specificity
7. Regulation of enzymatic activity
8. Assay methods
8.1. Trypsinogen activation assay
8.2. Cleavage of synthetic peptides
9. Congenital enteropeptidase deficiency
10. Acute pancreatitis
11. Acknowledgement
12. References


Enteropeptidase, a type II transmembrane serine protease, is localized to the brush border of the duodenal and jejunal mucosa. It is synthesized as a zymogen (proenteropeptidase) that requires activation by another protease, either trypsin or possibly duodenase. Active enteropeptidase then converts the pancreatic precursor, trypsinogen, to trypsin by cleavage of the specific trypsinogen activation peptide, Asp-Asp-Asp-Asp-Lys¯ Ile that is highly conserved in vertebrates. Trypsin, in turn, activates other digestive zymogens such as chymotrypsinogen, proelastase, procarboxypeptidase and prolipase in the lumen of the gut. The important biological function of enteropeptidase is highlighted by the manifestation of severe diarrhea, failure to thrive, hypoproteinemia and edema as a result of congenital deficiency of enteropeptidase activity in the gut. Conversely, duodenopancreatic reflux of proteolytically active enteropeptidase may cause acute and chronic pancreatitis.