Cleavage of peptide hormones by alpha 2-macroglobulin-trypsin complex and its relation to the pathogenesis and chemotherapy of acute pancreatitis
- PMID: 6162593
- DOI: 10.1016/0009-8981(81)90335-1
Cleavage of peptide hormones by alpha 2-macroglobulin-trypsin complex and its relation to the pathogenesis and chemotherapy of acute pancreatitis
Abstract
Access to the active site of alpha 2-macroglobulin bound proteinases by macromolecular substrates and inhibitors is likely to be influenced by steric favourability and flexibility, as well as by molecular size. Hydrolysis of pure porcine cholecystokinin-pancreozymin 39, a flexible single chain peptide, by alpha 2-macroglobulin-trypsin complex resulted in a rapid up to 6-fold increase in cholecystokinin bioactivity; alpha 2-macroglobulin-trypsin rapidly abolished the bioactivity of endogenous parathormone in human plasma. Inhibition of both reactions was completed by low concentrations of antipain and leupeptin; Trasylol (aprotinin), a single chain peptide with three disulphide bonds, was an ineffective inhibitor even in massive molar excess. These findings may provide an explanation for the disordered calcium homeostasis in severe acute pancreatitis and for the failure of Trasylol to reduce mortality; they suggest that sterically favourable low molecular weight inhibitors may provide effective specific chemotherapy for the disease.
Similar articles
-
Studies on the interaction of Trasylol (aprotinin) with trypsin-pancreatic secretory trypsin inhibitor (PSTI) complexes and with alpha 2-macroglobulin-trypsin-PSTI-complexes.Hoppe Seylers Z Physiol Chem. 1981 Dec;362(12):1653-6. Hoppe Seylers Z Physiol Chem. 1981. PMID: 6172356
-
An in vitro study of the influence of plasma protease inhibitors and aprotinin on trypsin-induced C3 cleavage in human serum.Biochim Biophys Acta. 1982 Dec 20;709(2):227-33. doi: 10.1016/0167-4838(82)90465-4. Biochim Biophys Acta. 1982. PMID: 6185150
-
Antiproteinase chemotherapy of acute experimental pancreatitis using the low molecular weight oligopeptide aldehyde leupeptin.Gut. 1982 Nov;23(11):939-43. doi: 10.1136/gut.23.11.939. Gut. 1982. PMID: 6182054 Free PMC article.
-
On the potential role of trypsin and trypsin inhibitors in acute pancreatitis.Adv Exp Med Biol. 1984;167:477-87. doi: 10.1007/978-1-4615-9355-3_42. Adv Exp Med Biol. 1984. PMID: 6201050
-
Trypsin inhibitors: promising candidate satietogenic proteins as complementary treatment for obesity and metabolic disorders?J Enzyme Inhib Med Chem. 2019 Dec;34(1):405-419. doi: 10.1080/14756366.2018.1542387. J Enzyme Inhib Med Chem. 2019. PMID: 30734596 Free PMC article. Review.
Cited by
-
Acute necrotising pancreatitis--a role for enterokinase.Int J Pancreatol. 1986 Oct;1(3-4):167-83. doi: 10.1007/BF02795243. Int J Pancreatol. 1986. PMID: 3316424 Review. No abstract available.
-
PSA-alpha-2-macroglobulin complex is enzymatically active in the serum of patients with advanced prostate cancer and can degrade circulating peptide hormones.Prostate. 2018 Aug;78(11):819-829. doi: 10.1002/pros.23539. Epub 2018 Apr 16. Prostate. 2018. PMID: 29659051 Free PMC article.
-
Survival after profound hypocalcaemia with tetany complicating severe haemorrhagic acute pancreatitis.Postgrad Med J. 1985 Jan;61(711):43-5. doi: 10.1136/pgmj.61.711.43. Postgrad Med J. 1985. PMID: 3991403 Free PMC article.
-
Impaired mononuclear phagocyte function in patients with severe acute pancreatitis: evidence from studies of plasma clearance of trypsin and monocyte phagocytosis.Dig Dis Sci. 1993 Jan;38(1):18-27. doi: 10.1007/BF01296768. Dig Dis Sci. 1993. PMID: 8420754
-
Alpha 2 macroglobulin state in acute pancreatitis. Raised values of alpha 2 macroglobulin-protease complexes in severe and mild attacks.Gut. 1991 Apr;32(4):430-4. doi: 10.1136/gut.32.4.430. Gut. 1991. PMID: 1709131 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical