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Inhibition of human pancreatic proteinases by human plasma α2-antiplasmin and antithrombin

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Published/Copyright: June 1, 2005
Biological Chemistry
From the journal Volume 385 Issue 5

Abstract

Human plasma α1-antitrypsin inhibits human pancreatic trypsin, chymotrypsin and elastase, which are massively released into the blood stream during acute pancreatitis. To examine whether the plasma proteins of individuals with genetic deficiency of α1-antitrypsin are protected against the deleterious action of these enzymes by other inhibitors, we have tested their inhibition by α2-antiplasmin and antithrombin. We have determined the inhibition rate constants k and calculated d(t), the in vivo inhibition time. Surprisingly, trypsin is inhibited faster by α2-antiplasmin [k=2.510[6] M[-1]s[-1], d(t)=2.3 s] and antithrombin [k=1.710[5] M[-1]s[-1], d(t)=5.8 s] than by α1-antitrypsin [d(t)=17 s or 116 s in α1-antitrypsinsufficient or α1-antitrypsindeficient individuals, respectively]. Low molecular weight heparin accelerates the inhibition of trypsin by antithrombin by a factor of 16 [d(t)=0.36 s]. Antithrombin and α2-antiplasmin are not physiological inhibitors of chymotrypsin and elastase. These enzymes are, however, physiologically inhibited by α1-antitrypsin and α1-antichymotrypsin even in α1-antitrypsindeficient individuals. We conclude that (i) low molecular weight heparin may be helpful in the management of acute pancreatitis, and (ii) genetically determined α1-antitrypsin deficiency probably does not lead to a significantly increased risk of plasma protein degradation during this disease.

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Published Online: 2005-06-01
Published in Print: 2004-05-14

Copyright © 2004 by Walter de Gruyter GmbH & Co. KG

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