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Official Full Name
Enteropeptidase (also called enterokinase) is an enzyme produced by cells of the duodenum and involved in human and animal digestion. It is secreted from intestinal glands (the crypts of Lieberkühn) following the entry of ingested food passing from the stomach. Enteropeptidase converts trypsinogen (a zymogen) into its active form trypsin, resulting in the subsequent activation of pancreatic digestive enzymes. Absence of enteropeptidase results in intestinal digestion impairment.
enterokinase; enteropeptidase; EC; 9014-74-8

Product Name
EC No.
CAS No.9014-74-8
CAS No.9014-74-8
SourceCalf intestine
CAS No.9014-74-8
SourceE. coli
CAS No.9014-74-8
SourceCHO cells
CAS No.9014-74-8
SourcePorcine intesti...
CAS No.9014-74-8
SourceBovine intestin...
Related Protocols
enterokinase -Enzymatic Assay Protocol
Related Reading


Pancreatic enzymes are secreted in an inactive state. In 1899, Schepovalnikoff discovered that duodenal secretions could activate the pancreatic proteolytic enzymes. They believe that this activator in intestinal secretions is "an enzyme of enzymes" and named it enterokinase (EK). Kunitz showed that crystalline trypsinogen can be completely converted to trypsin by EK at a pH of 5.2-6.0. He purified EK from the liquid content of pig duodenum by fractionation precipitation with ammonium sulfate. After a series of analyses, it was shown that EK contains neutral sugars such as fructose, mannose, and galactose, as well as amino sugars, glucosamine, and galactosamine. These results indicate that EK was a glycoprotein.

EK is now designated as enteropeptidase (E.C. In addition to its ability to convert trypsinogen into trypsin, it can also counteract the effect of trypsin inhibitors on trypsin. However, other researchers have shown that EK has no significant effect on trypsin inhibitors. EK seems to act as a peptidase to cleave a valyl peptide from the amino terminus of trypsinogen. Bile acids have been shown to be important in EK activation of trypsinogen in rats and humans; disorders of trypsinogen activation have been observed in patients with intrahepatic biliary atresia. In humans, enterokinase is present in the mucosa of the first and second portion of the duodenum, and intraluminal EK does not appear to originate by simple desquamation or turnover of the intestinal mucosa. 

Enterokinase active site Figure 1. Enterokinase active site

Role of EK in Pancreatitis

The exact pathogenesis of acute pancreatitis is still unclear. Some scientists believe that there is a common channel between the common bile duct and the pancreatic duct, while others believe that acute pancreatitis is caused by bile duct obstruction. Duodenopancreatic reflux of the EK-rich duodenal contents causes the intrapancreatic activation of trypsinogen, leading to acute pancreatitis. Slow, low-pressure intraductal injection of EK in dogs and rats can cause acute pancreatitis and hyperamylasemia. EK may also increase the protein content of the pancreas by increasing the content of proteolytic enzymes. If 5-azacytidine and cycloheximide are given, it can prevent the EK effect from affecting the pancreatic protein and amylase content. EK seems to play an important role in acute experimental and clinical pancreatitis.

EK Deficiency

As mentioned earlier, EK is responsible for converting inactive trypsinogen into trypsin, and then trypsin will activate other proenzymes, such as chymotrypsinogen, procarboxy, peptidases, and proelastase, so this seems to be the cause of obvious protein malabsorption and impaired development and growth due to deficiency of EK. Since the first case of congenital EK deficiency was reported in 1969, more and more cases of EK deficiency have been reported. These patients present with diarrhea, developmental delay, edema, vomiting, hypoproteinemia and so on. Pancreatic proteolytic enzymes are essential for the absorption of vitamin B12, pancreatic proteolytic enzymes separate B12 from R-protein, thereby enabling B12 to attach to intrinsic factor. In cases of chronic pancreatic insufficiency, malabsorption of vitamin B12 has been documented. After pancreatic replacement therapy in all cases of EK deficiency with anemia, hemoglobin levels have improved. It has been suggested that the anemia in patients with EK deficiency was due to malabsorption and deficiency of vitamin B12.

However, in most of these conditions, pancreatic insufficiency may be due to impaired secretin and cholecystokinin release. Impaired release of cholecystokinin in celiac sprue may lead to gallbladder inertia and slow enterohepatic circulation of bile salts. It has been suggested that bile salts are very important for EK to activate trypsinogen, and trypsinogen activation disorders have been observed in patients with intrahepatic biliary atresia. If this is true, then the impaired release of cholecystokinin due to gallbladder inertia in patients with celiac disease may cause steatorrhea by interfering with the action of EK. However, other researchers have shown that the increase in duodenal juice after secretin and pancreatin stimulation has nothing to do with bile salt concentration. The relationship between secretin, cholecystokinin, bile salts and EK is not fully understood.


  1. Mann, N.S.; Mann, S.K. Enterokinase. Experimental Biology and Medicine. 1994, 206(2): 114-118.
  2. Kitamoto, Y.; et al. Enterokinase, the initiator of intestinal digestion, is a mosaic protease composed of a distinctive assortment of domains. Proceedings of the National Academy of Sciences. 1994, 91(16): 7588-7592.

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