Overview:
      Until recently, two criteria have been used to classify a lipolytic enzyme as a "true" lipase.  First, its activity should sharply increase
      as soon as the triglyceride substrate forms an emilsion.  [2]  This phenomenom is termed "interfacial activation".  It should also
      contain a "lid", which is a surface loop of the protein covering the active site of the enzyme and moving away on contact with the
      interface.  However, this criteria is unsuitable for classification, mainly because a number of exceptions exist where enzymes contain
      a lid but do not exhibit interfacial activation. [3].  Therefore, lipases are simply defined as carboxylesterases catalyzing the hydrolysis and synthesis of long-chain acylglycerols.

      Lipases (triacylglycerol lipases)  are enzymes which have been employed to carry on hydrolysis of triglycerides with production of
      fatty acids.  However, these enzymes also display catalytic activity towards a large variety of alcohols and acids in ester synthesis
      reactions when the water acitvity is very low.  At least 21 sequences of triacylglycerol lipases have been published.  Of these, nine are
      from mamalian spiecies and twelve are from microbial species. [2]    Enzymes that play a role in the human system are hepatic, the
      gastric, and the pancreatic lipases.[3]  A mammalian acidic lipase which belongs to a family of lipases that share the abiltiy to be
      resistant and activate under acidic conditions is the human gastric lipase.  The human gastric lipase is secreted by chief cells of the
      fundic part of the stomach, where it initiates the digestion of triacylglycerols.  Another important enzyme is the  human pancreatic
      lipase which was the first mammalian lipolytic enzyme to be solved structurally.  Pancreatic lipases are enzymes that participate in
      the hydrolysis of dietary lipids and subsequent intestinal absorption..  Under physiological conditions, however, dietary fat digestion
      is possible only if a small ancillary protein, colipase is present.  Colipase prevents lipase from denaturation at the water-lipid
      interface.  Yet another quite vital enzyme, hepatic lipases which are plasma proteins involved in metabolism of differnt lipoprotein
      classes and are found in the liver.[6]
 
 

 Function & Role by Kimberly Cizmar

Introduction
Function and Role
Works Cited

Introduction:

Fats require special digestive action before absorption because the end products must be carried in a water medium (blood and lymph) in which fats are not soluble. The majority of dietary lipids are in a class called triacylglycerols and are attacked by lipases to yield simple fatty acids and glycerol, molecules which can permeate the membranes of the stomach and small intestine for use by the body. Lipases are enzymes produced by the liver, pancreas, stomach, or by plant seeds, that are the primary digestant of lipids [2].

Gastric lipase, secreted by the stomach lining, has a pH value for optimal activity around neutrality and would appear, therefore, to be essentially inactive in the strongly acidic environment of the stomach. It is suggested that this enzyme is more important for infant digestion since the gastric pH in infancy is much less acidic than later in life.  Although little actual fat digestion occurs in the stomach, gastric lipase does digest already emulsified fats such as in egg yolk and cream [3].

Most lipid digestion in the adult occurs in the upper loop of the small intestine and is accomplished by a lipase secreted by the pancreas,commonly reffered to as pancreatic lipase.

Pancreatic enzymes, secreted into the intestine from the pancreas, generate free fatty acids and a mixtures of mono- and diacylglycerols from dietary triacylglycerols. Pancreatic lipase degrades triacylglycerols at the 1 and 3 positions sequentially to generate 1,2-diacylglycerols and 2-acylglycerols.

                               Figure 1: Example of gastric lipase. [5]                                                                                                          Figure 2:  Example of pancreatic lipase. [5]
 
 

The pancreatic lipase is constituted by two structural domains: a large N-terminal domain which contains the catalytic site shielded by the lid domain (Winkler et al., 1990), and a small C-terminal domain which is involved in colipase binding.

Function:

First step:     Emulsification of the lipids.

                        The large fat molecule presents comparatively small surfaces for the lipase to work on, so the process of emulsification by the
                        action of bile produced by the liver is necessary. Bile breaks down the large fat molecule to tiny droplets which provide lipase with
                        an enormously increased surface to work on. This action takes place in the small intestine and the lipase involved here is a part of
                        the pancreatic secretion.

Second Step:     Attachment of Colipase

                             Colipase:
                                - prevents lipase from denaturation at the water-lipid interphase
                                - reverses the inhibitory effects of bile salts on lipase binding at this interphase [1].

[6]
 
 
 
 

Step 3:                                                               Step 4:                                                               Step 5:
Access to the active site serine                         When lipase binds to the lipid, the                    Compare the position of the helix in                              is blocked by a helix.                                        helix moves allowing the substrate                 free enzyme and in the
                                                                              to bind at the active site.                                  enzyme-substrate complex.  [1].
 
 

Sixth Step:     Hydrolytic activity of the lipase on the ester bond after a part of the monosubstrate
                         has been bound in the elongated  hydrophobic cleft and the monsubstrate has been
                         orientated correctly on the active site.
 
 

                                                  Figure 6: Pancreatic lipase hydrolysis of triacylglycerols.
                                                        (hydrolysis of ester bonds)
 

Factors contributing to the effeciency of lipase:
           - Sodium chloride.
           - Calcium ions - improve thermal stability.
 
 
 
 
 
 
 

Works Cited:

[1]  Derewenda, AM   Brzozowski, AM Lawson, and ZS Derewenda Biochemistry 31 1532 (1992).

[5]  Image Library of Biological Macromolecules (Protein Data Bank) by Jena

[2]  King, Dr. Michael W.  The Medical Biochemistry Page
                http://web.indstate.edu/thcme/mwking/fatty-acid-oxidation.html.

[3]  "Lipase." Factmonster.com. © 2000 Learning Network. http://www.factmonster.com/ce6/sci/A0829915.html. (November 5, 2001).

[6]  Ruben, Thomas and Dennis, Edward A..  Methods in Enzymology Volume 284 Lipases Part A Biotechnology.  Academic Press, New
            York, 1997.