ACETALDEHYDE INHIBITS CHYMOTRYPSIN AND SERUM ANTI-CHYMOTRYPSIN ACTIVITY

Citation
As. Brecher et Mp. Yang, ACETALDEHYDE INHIBITS CHYMOTRYPSIN AND SERUM ANTI-CHYMOTRYPSIN ACTIVITY, Journal of investigative medicine, 46(4), 1998, pp. 146-152
Citations number
26
Categorie Soggetti
Medicine, Research & Experimental","Medicine, General & Internal
ISSN journal
10815589
Volume
46
Issue
4
Year of publication
1998
Pages
146 - 152
Database
ISI
SICI code
1081-5589(1998)46:4<146:AICASA>2.0.ZU;2-U
Abstract
Background: Chymotrypsin (CT) and CT-like enzymes contribute to the dy namics of metabolism by their participation in digestion, peptide horm one generation and catabolism, fertilization of ova and inhibition of thrombin-induced platelet aggregation, among other processes. The freq uency of pancreatitis is observably higher in alcoholics, and pancreat ic enzymes have been associated with localized vascular damage, thromb osis and pancreatic necrosis. Methods: Since CT is a major pancreatic enzyme and may serve as a link between pancreatitis, coagulopathy, and alcoholism, the effect of acetaldehyde (AcH) the primary metabolite o f ethanol, upon the enzyme and upon the influence of human serum there on was studied. Results: It was observed that CT activity upon glutary l-L-phenylalanine-b-naphthylamide was inhibited to the extent of 23.7% , 52.5%, and 96.7% by 44.7, 89.4, and 447 mmol/L AcH in a fluorometric assay whereby the enzyme was dialyzed to remove excess AcH prior to a ssay. The p values were < 0.04. Aliquots of human serum (10 mu L, 20 m u L, 30 mu L, 40 mu L, 50 mu L, and 100 mu L) inhibited 40 mu g of CT by 13%, 37.7%, 65.3%, 89.8%, and 92.8%, respectively (n = 6; p = < 0.0 5). The serum did not hydrolyze the fluorogenic substrate. On the othe r hand, AcH added to serum at 447, 224, 112, or 56 mmol/L resulted in 42.6%, 42.6%, 52.9%, and 60.3% inhibition of CT relative to a 69.1% in hibition of the enzyme by serum alone (n = 6; =p < 0.01). Conclusions: These data show that AcH clearly decreases the antichymotryptic activ ity of serum (consisting of alpha(1)-proteinase inhibitor, alpha(1)-an tichymotrypsin, and alpha(2)-macroglobulin). The incomplete inactivati on of chymotrypsin by serum and partial inactivation of CT inhibitor(s ) by AcH suggest the possibility that CT leaked into the circulation, tin alcoholic pancreatitis) may be available in blood to lower the clo tting potential induced by thrombin-activated platelets, and that a gr eater amount of CT might be available in the blood of alcoholics, ther eby contributing, in part, to the prolongation of clotting times.