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胆盐刺激的脂肪酶:受磷脂抑制和受磷脂酶 A 缓解。

Bile salt stimulated lipase: Inhibition by phospholipids and relief by phospholipase A.

机构信息

James Fairfax Institute of Paediatric Nutrition, The Children's Hospital at Westmead, NSW 2145, Australia.

The University of Sydney, School of Life and Environmental Sciences, NSW 2006, Australia.

出版信息

J Cyst Fibros. 2017 Nov;16(6):763-770. doi: 10.1016/j.jcf.2017.07.005. Epub 2017 Jul 22.

Abstract

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 (PLA; 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 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 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 could improve patient health with adequate manipulation of phospholipid and lysophospholipid concentrations in the intestinal fluid.

摘要

简介

胆汁盐刺激脂肪酶(BSSL;酶委员会(EC)编号 3.1.1.13)一直是候选的脂肪酶,用于改善胰腺功能不全的酶治疗;然而,其疗效几乎不存在。我们假设,类似于胰腺脂肪酶,BSSL 被磷脂抑制,这种抑制被磷脂酶 A(PLA;EC 3.1.1.4)解除,本研究旨在探讨这种可能性。

材料与方法

使用甘油三酯和磷脂酰胆碱(PC)或溶血磷脂酰胆碱(LPC)/胆汁盐混合胶束的合成乳液作为肠消化介质的模型。还探索了 PLA 处理含有 PC 的系统对 BSSL 活性的影响。自动滴定在恒定 pH(pH -stat)和核磁共振(NMR)光谱用于测量脂肪分解的速率和鉴定产物。

结果

PC 对 BSSL 活性有抑制作用,而 LPC 仅在 LPC/胆汁盐浓度比高于 0.3 时才具有抑制作用。尽管 PLA 具有完全的磷脂水解作用,但仅在低于该比值时,PLA 处理才能解除抑制。因此,LPC 在较高浓度下具有抑制作用。

结论

这些结果可能暗示胰腺外分泌功能不全患者的酶治疗设计需要改变。通过适当控制肠液中磷脂和溶血磷脂的浓度,用 PLA 补充 BSSL 可以改善患者的健康状况。

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