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
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.