Deficiency of arginine esterase in cystic fibrosis of the pancreas: demonstration of the proteolytic nature of the activity.

Proteolytic activity, defined as the hydrolysis of peptide bonds involving the carboxyl 
group of L-arginine, in plasma of patients with cystic fibrosis, heterozygotes, 
and control subjects has been assayed using a fluorometric method with 
protamine as the substrate and fluorescamine as the reagent. The mean 
total proteolytic activity in plasma of patients with cystic fibrosis was 
approximately one-half the mean total activity in control subjects and heterozygotes. 
The mean proteolytic activity inhibited by soybean trypsin inhibitor in plasma 
of patients with cystic fibrosis was approximately one-third that of control 
subjects and heterozygotes. The relationship of arginine esterase activity to proteolytic 
activity was investigated. The pH optimum and action of reversible and 
irreversible inhibitors were similar for both activities, suggesting that the arginine 
esterase activity and proteolytic activity represent similar catalytic entities. These findings 
are consistent with our hypothesis that the basic defect in cystic 
fibrosis may reside in the deficiency of a proteolytic enzyme which 
results in the accumulation of the various cationic macromolecular "factors" described 
by other investigators in serum of patients with cystic fibrosis. The 
demonstration of a deficiency of proteolytic activity as assayed by the 
hydrolysis of protamine, a cationic polypeptide, could explain the presence of 
ciliotoxic cationic protein or polypeptide factors in serum of patients with 
cystic fibrosis and may, in some unknown manner, be related to 
the clinical manifestations of the disease. 