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 |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Phospholipase A biology Triglyceride business.industry Phospholipid 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Phospholipase A2 Lysophosphatidylcholine chemistry Biochemistry Phosphatidylcholine Pediatrics Perinatology and Child Health biology.protein Lipolysis Medicine lipids (amino acids peptides and proteins) 030211 gastroenterology & hepatology Lipase business |
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 |
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