Activity levels and properties of acid α-glucosidase from liver and neutral α-glucosidase from sera of cystic fibrosis patients and controls

Abstract

The average activity levels of acid α-glucosidase are comparable in liver supernatant fluids for 15 cystic fibrosis patients and 12 controls (401 ± 131 and 347 ± 109 nmol/h/mg protein, respectively) and no significant differences were found for the cystic fibrosis and control liver acid α-glucosidases in their (a) apparent K m values for the 4-methylumbelliferyl substrate (1.1 mmol/1), (b) pH optima (4.2) and thermostability curves and (c) isoelectric profiles (one form with an isoelectric point of 4.5 ± 0.2). In contrast, average neutral α-glucosidase activity levels were significantly increased ( p < 0.0002) in sera from 21 cystic fibrosis patients compared to 15 controls (10.7 and 2.7 nmol/h/ml). This increased activity is not due to (a) different stability upon storage at −20°C, (b) the presence of activators in cystic fibrosis sera or inhibitors in normal sera (as determined by mixing studies), (c) altered K m values or (d) altered pH optima curves. Cystic fibrosis serum neutral α-glucosidase appears to be more thermostable and has a consistently altered isoelectric profile (greater percentage of activity above pI 4.8) when compared to the normal serum enzyme. This altered isoelectric composition may reflect changes in neutral α-glucosidase which contribute to its increased activity in cystic fibrosis sera.