Introduction: Bile salt stimulated lipase (BSSL; Enzyme Commission (EC) number 3.1.1.13) has been a candidate triglyceridase for improving enzyme therapy for pancreatic insufficiency; however, its efficacy is near absent. We hypothesise that similarly to pancreatic lipase, BSSL is inhibited by phospholipids and this inhibition is relieved by Phospholipase A2 (PLA2; EC 3.1.1.4), and the present study was undertaken to explore this possibility.
Materials and methods: Synthetic emulsions of triglyceride and phosphatidylcholine (PC) or lysophosphatidylcholine (LPC)/bile salt mixed micelles were used as a model of intestinal digestion-media. The effect of PLA2 treatment of systems containing PC on BSSL activity was also explored. Automatic titration at constant pH (pH-stat) and nuclear magnetic resonance (NMR) spectroscopy were used to measure the rate and identify products of lipolysis.
Results: PC was inhibitory to BSSL activity, while LPC became inhibitory only above an LPC/bile salt concentration ratio of 0.3. PLA2 treatment relieved the inhibition only below this ratio, despite its complete phospholipid-hydrolysing action. Thus, LPC had an inhibitory effect at higher concentrations.
Conclusions: These results may implicate a change in the design of enzyme therapy in patients with pancreatic exocrine insufficiency. Supplementation of BSSL with PLA2 could improve patient health with adequate manipulation of phospholipid and lysophospholipid concentrations in the intestinal fluid.
Keywords: Bile salt stimulated lipase; Cystic fibrosis; Enzyme therapy; NMR spectroscopy; Pancreatic insufficiency; Titrimetric enzyme assay.
Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.