The lid is a residue helical structure that protects the oxyanion hole. The lid yellow is especially important to substrate binding as it undergoes a dramatic shift that alters the secondary structure of the lipase binding site from a active site in red to an active site in blue, triacylglyceride in spacefill [8] see Lipase lid morph for an animation of this transition.
The lid opening is accompanied by a change in secondary structure from a mostly beta-extended confirmation to a structure where more than half the active site is formed from alpha helices [9].
Lipase is activated by colipase, a coenzyme that binds to the C-terminal, non-catalytic domain of lipase. Colipase is a 10kDa protein that is secreted by the pancreas in an inactive form. It has five conserved shown in yellow [10] , and 2 - a hydrophilic surface site of lipase C-terminal interaction- shown in blue and a hydrophobic surface contains multiple hydrophobic loops to bridge the lipid- shown in white [11].
Trypsin will then activate colipase before the cofactor can interact with lipase. Colipase must be present for activation of lipase and acts as a bridge between lipase and the lipid. When colipase binds, active lipase is stabilized for the hydrophobic interaction with triacylglycerides [12].
Colipase and lipase are opposite of the active site on the C-terminal contacts are regions of pink and yellow, with water molecules shown in darker blue. The enzymes are bound by polar interactions such as , and [14]. In the presence of colipase, the enzyme is activated which moves the shown in red, active site in green which is composed of amino acids The N-terminal flap moves in a concerted fashion along with the C-terminal domain to reveal the active site green , allowing it to bind with a substrate.
It is hypothesized that this flexibility may have significance in binding the colipase-lipase complex with the water-lipid interface. Lipase activation at the lipid-water interface of triacylglycerides, in the presence of colipase and bile salts, is known as interfacial activation. For the hydroloysis reaction to take place, colipase anchors lipase to the lipid-water membrane of the micelle which causes a surface change on lipase.
Colipase's four hydrophobic loops interact with the hydrophobic atmosphere of the triacylglyceride. This initiates active site binding to the lipid, and lid opening to reveal a more hydrophobic environment for the triacylglycerol. This in turn, allows the triacylglycerol to interact with key active site residues like the catalytic triad. A diverse array of lipase enzymes can be found in nature. Moreover, this study identifies, for the first time, residues that contribute to the substrate preference of pancreatic lipase for medium- and long-chain triglycerides.
We are greatly indebted to Dr Charles C. We are grateful to D. Baty, P. Chames and I. Crenon for helpful discussions. Google Scholar. Google Preview. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account.
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Modification of pancreatic lipase properties by directed molecular evolution. Oxford Academic. Paule Deprez-Beauclair. Noella Silva. Lourdes Infantes. Brigitte Kerfelec 5. E-mail: brigitte. Revision received:. Select Format Select format. Permissions Icon Permissions. Abstract Cystic fibrosis is associated with pancreatic insufficiency and acidic intraluminal conditions that limit the action of pancreatic enzyme replacement therapy, especially that of lipase.
Open in new tab Download slide. Table I Apparent affinity of mutant lipases for colipase. K Dapp nM. HuPL 2. Open in new tab. Table II Kinetic parameters of wild type and variant lipases on tributyrin and trioctanoin. K m app mM. Search ADS. Di Lorenzo. Edited by Eva Petersen. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals. Issue Section:. Download all slides. View Metrics. Email alerts Article activity alert. New issue alert. In progress issue alert.
Receive exclusive offers and updates from Oxford Academic. Related articles in Web of Science Google Scholar. Citing articles via Web of Science 7. Orlistat is used to treat obesity by blocking lipase from breaking down fats so the body does not absorb them. Digestive enzymes: Digestive enzymes, including papain, pepsin, betaine HCL, and hydrochloric acid, can destroy the lipase enzymes.
Enteric-coated lipase enzyme products are protected against destruction by stomach acid. Serum lipase as an early predictor of severity in pediatric acute pancreatitis. J Pediatr Gastroenterol Nutr. Pancreatic enzyme therapy for pancreatic exocrine insufficiency. Curr Gastroenterol Rep. Du J, Wang Z. Therapeutic potential of lipase inhibitor orlistat in Alzheimer's disease.
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