The kinetic investigation of the inhibition of human pancreatic trypsin 1, trypsin 2 and chymotrypsin A by mucus proteinase inhibitor, eglin c and aprotinin reveals that (i) the first protein is a potent inhibitor of chymotrypsin A (kass. = 1.4×106 M-1·s-1, Ki = 71 pM) but forms loose complexes with trypsin 1 (Ki = 0.5 μM) and trypsin 2 (Ki = 18 nM), (ii) eglin c does not inhibit the two trypsins but forms a tight complex with chymotrypsin A (kass. = 3.3×106 M-1·s-1, Ki < 0.1 nM) and (iii) aprotinin is a potent inhibitor of trypsin 1 (kass.=1×105 M-1·s-1, Ki<0.2 nM) and trypsin 2 (kass. = 2.4×105 M-1·s-1, Ki < 1 nM) but forms a loose complex with chymotrypsin A (Ki = 0.17 μM). These data, together with those published previously on human pancreatic elastase, suggest that a cocktail of aprotinin+eglin c might be a better intensive-care drug for acute pancreatitis than aprotinin alone, because it will efficiently inhibit all four human pancreatic proteinases. On the other hand, human gastric juice inactivates mucus proteinase inhibitor by pepsin-mediated cleavage. This indicates that the fraction of mucus proteinase inhibitor that reaches the stomach following aerosol delivery to cystic fibrosis patients does not reach the duodenum in an active form and, therefore, does not aggravate the pancreatic insufficiency of these patients.
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January 1996
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Research Article|
January 15 1996
Inhibition of human pancreatic proteinases by mucus proteinase inhibitor, eglin c and aprotinin Available to Purchase
Didier BELORGEY;
Didier BELORGEY
*Laboratoire d'Enzymologie, INSERM U392, Université Louis Pasteur de Strasbourg, F-67400 Illkirch, France
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Sylvie DIRRIG;
Sylvie DIRRIG
*Laboratoire d'Enzymologie, INSERM U392, Université Louis Pasteur de Strasbourg, F-67400 Illkirch, France
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Michelle AMOURIC;
Michelle AMOURIC
†Groupe de Recherche sur les Glandes Exocrines, Faculté de Médecine, F-13385 Marseille, France
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Catherine FIGARELLA;
Catherine FIGARELLA
†Groupe de Recherche sur les Glandes Exocrines, Faculté de Médecine, F-13385 Marseille, France
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Joseph G. BIETH
Joseph G. BIETH
‡
*Laboratoire d'Enzymologie, INSERM U392, Université Louis Pasteur de Strasbourg, F-67400 Illkirch, France
‡To whom correspondence should be addressed.
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Publisher: Portland Press Ltd
Received:
February 03 1995
Revision Received:
August 30 1995
Accepted:
September 12 1995
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1996
1996
Biochem J (1996) 313 (2): 555–560.
Article history
Received:
February 03 1995
Revision Received:
August 30 1995
Accepted:
September 12 1995
Citation
Didier BELORGEY, Sylvie DIRRIG, Michelle AMOURIC, Catherine FIGARELLA, Joseph G. BIETH; Inhibition of human pancreatic proteinases by mucus proteinase inhibitor, eglin c and aprotinin. Biochem J 15 January 1996; 313 (2): 555–560. doi: https://doi.org/10.1042/bj3130555
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