Measurement of 4-methylumbelliferyl p-guanidinobenzoate (
MUGB)-hydrolyzing activity in the plasma of normal controls,
cystic fibrosis (CF) heterozygotes, and CF homozygotes did not support previously reported (35) differences in
MUGB-hydrolyzing activity. We identified human
plasma albumin as the major source of
MUGB-hydrolyzing activity by comparison of our plasma results to those obtained with physiologic concentrations of commercial
albumin samples. Substantiating evidence was obtained from gel filtration experiments and correlation of
albumin levels in CF plasma with
MUGB titers. We found essentially no proteolytic activity towards dinitrophenylprotamine
sulfate associated with commercial
albumin samples. It appears that the reaction between
human albumin and
MUGB represents a weak
esterase activity, perhaps involving the acylation of a specific site(s) on the
protein.
Hypoalbuminemia has been documented (8) in some CF patients. Low
albumin concentrations, indicated by
MUGB titers less than 190 nmole
methylumbelliferone/ml plasma, were found in 42% of CF homozygotes, 6% of heterozygotes, and 4% of controls. Gel filtration studies of a normal amniotic fluid supernatant indicated that
albumin was the major
MUGB-hydrolyzing substance in this fluid. We conclude that
MUGB abnormalities are not associated with the basic gene defect in CF and cannot be used as the basis of a test for intrauterine or heterozygote detection.