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大鼠和人胰腺甘油三酯脂肪酶的分子机制

Molecular mechanisms of rat and human pancreatic triglyceride lipases.

作者信息

Lowe M E

机构信息

Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.

出版信息

J Nutr. 1997 Apr;127(4):549-57. doi: 10.1093/jn/127.4.549.

DOI:10.1093/jn/127.4.549
PMID:9109604
Abstract

Dietary fats affect health and disease. The assimilation of dietary fats into the body requires that they be digested by lipases. One lipase, pancreatic triglyceride lipase, is essential for the efficient digestion of dietary fats. Pancreatic triglyceride lipase is the archetype of the lipase gene family that includes two homologues of pancreatic triglyceride lipase, pancreatic lipase-related proteins 1 and 2. In recent years, important advances have been made in delineating the mechanisms of lipolysis. The cDNA sequences encoding pancreatic triglyceride lipase and the related proteins have been described. The tertiary structure of human pancreatic triglyceride lipase has been determined alone and in a complex with colipase, a pancreatic protein required for lipase activity in the duodenum. This structural information has allowed the rational design of site-specific mutants of pancreatic triglyceride lipase. Together with the structural information, these mutants have greatly advanced our understanding of the molecular details governing lipolysis. This review describes these studies, which will eventually provide the background for the rational design of nutrition therapy in patients with pancreatic insufficiency and fat malabsorption.

摘要

膳食脂肪影响健康与疾病。膳食脂肪被人体吸收需要经脂肪酶消化。其中一种脂肪酶,即胰脂肪酶,对膳食脂肪的有效消化至关重要。胰脂肪酶是脂肪酶基因家族的原型,该家族包括胰脂肪酶的两个同源物,即胰脂肪酶相关蛋白1和2。近年来,在阐明脂肪分解机制方面取得了重要进展。已描述了编码胰脂肪酶及相关蛋白的cDNA序列。已确定了人胰脂肪酶的三级结构,且该结构是其单独存在时以及与辅脂酶(一种十二指肠中脂肪酶活性所需的胰腺蛋白)形成复合物时的结构。这些结构信息使得能够合理设计胰脂肪酶的位点特异性突变体。与结构信息一起,这些突变体极大地推进了我们对脂肪分解分子细节的理解。本综述描述了这些研究,这些研究最终将为胰腺功能不全和脂肪吸收不良患者营养治疗的合理设计提供背景。

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