Bile salt stimulated lipase: Inhibition by phospholipids and relief by phospholipase A2

Autor: Philip W. Kuchel, Elena Venuti, Kevin J. Gaskin, Caron Blumenthal, Dmitry Shishmarev, Shoma Dutt
Rok vydání: 2017
Předmět:
Zdroj: Journal of Cystic Fibrosis. 16:763-770
ISSN: 1569-1993
DOI: 10.1016/j.jcf.2017.07.005
Popis: 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 A 2 (PLA 2 ; 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 PLA 2 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. PLA 2 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 PLA 2 could improve patient health with adequate manipulation of phospholipid and lysophospholipid concentrations in the intestinal fluid.
Databáze: OpenAIRE