Inactivation of human lipase by proteases.
To determine if human lipase is inactivated by trypsin and chymotrypsin, we intubated 22 human subjects with an oroduodenal tube and stimulated pancreatic secretion with cholecystokinin octapeptide. The duodenal aspirate from each subject was divided into a control and a test sample and incubated in a 37 degrees C water bath for 2 h. An inhibitor of trypsin or chymotrypsin or more of one of these enzymes was added to the test sample. We found that the loss of lipase activity was partly prevented by inhibiting trypsin with aprotinin (910 KU/ml; P = 0.03) and was accelerated by adding bovine trypsin (2.5 mg/ml; P = 0.01). Inhibiting chymotrypsin with turkey egg white (2.5 mg/ml) totally abolished the loss of lipase activity (P = 0.01), and addition of bovine chymotrypsin (5 mg/ml) accelerated the loss of lipase activity more than adding trypsin (P = 0.01). After inhibiting chymotrypsin (to maintain lipase activity), increasing trypsin activity by adding a single or repeated doses of trypsin did not decrease lipase activity. Conversely, the addition of a single dose of chymotrypsin after inhibiting trypsin activity markedly decreased lipase activity (P less than 0.004). In conclusion, chymotrypsin is a more potent inactivator of human lipase than trypsin; chymotrypsin inactivates lipase in the absence of trypsin, but trypsin inactivation of lipase requires chymotrypsin.
Thiruvengadam
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Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota.
DiMagno
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EP
D000328:Adult; D000368:Aged; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D002417:Cattle; D002918:Chymotrypsin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004386:Duodenum / Q000187:drug effects / Q000201:enzymology*; D004529:Egg White; D005260:Female; D006801:Humans; D007700:Kinetics; D008049:Lipase / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D012844:Sincalide / Q000494:pharmacology; D014357:Trypsin / Q000378:metabolism*; D014361:Trypsin Inhibitors; D014422:Turkeys
D014361:Trypsin Inhibitors; D007611:Aprotinin; D008049:Lipase; D002918:Chymotrypsin; D014357:Trypsin; D012844:Sincalide