Protease deficiency in plasma of patients with cystic fibrosis. Reduced reaction of 4-methylumbelliferylguanidinobenzoate with plasma of patients with cystic fibrosis.

Protease activity in plasma is assayed using 4- methylumbelliferylguanidinobenzoate. The assay is 
modified by carrying out the reaction in the presence and absence 
of benzamidine, a competitive inhibitor of trypsin-like proteases. The parameters of 
the assay are described in detail. Using this assay, our earlier 
demonstration of a deficiency of protease activity in plasma of patients 
with cystic fibrosis is confirmed. The activity, corrected for the nonspecific 
hydrolysis of 4- methylumbelliferylguanidinobenzoate by benzamidine, is expressed as nanomoles of 
4-methylumbelliferone released per milliliter plasma. Under standard conditions, the activity in 
plasma activated with chloroform-ellagic acid was 127.2 +/- 23.1 in 7 
controls, 70.4 +/- 11.7 in 11 obligate heterozygotes, and 48.7 +/- 
16.6 in 12 patients with cystic fibrosis. Identical results were obtained 
when unactivated plasma was used. These data demonstrate that the judicious 
use of specific inhibitors such as benzamidine might be useful in 
assaying low levels of protease activity in crude systems. 