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Pancreatic Lipase

Introduction

Pancreatic lipase 1hpl (EC 3.1.1.3) is a an enzyme involved with the digestion of triacylglycerols (fats) in digestion. It is secreted by the pancreas into the duodenum where it participates in the initial stages of breaking down fats ^[1]

Structure

The of the human pancreatic lipase has not been published yet but 1hpl is the horse pancreatic lipase enzyme that is thought to have a similar structure and function. Lipase has two of 449 amino acid residues interacting with one each. The calcium ion shows that the molecule is located between acidic residues Arg, Asp and Glu. The molecule has a varying degree of interspersed within the molecules ^[2]. This is important because the enzyme actively digests at the lipid-water interface of the fatty micelles, requiring stability in both polar and non polar environments ^[3]. In the , the N-terminal domain has the hydrolase alpha/beta folding structure, consisting of an alpha-beta sheet consisting of 8 strands connected by helices. The C-terminal domain (enzyme colipase binds) has a beta-sheet sand which folding pattern ^[4] The of the lipase molecule is found in the N-terminal domain (residues 1-336) and contains a consisting of a Ser-His-Arg for the ester hydrolysis reaction (similar to that of a serine protease). The active site is covered by a 25-residue helical 'lid' blocking the binding site, unless appropriate conditions ^[5].

Function

Pancreatic lipase initiates the breakdown of triacylglycerols into 2-monoacylglycerols and fatty acids. Consequently, lipase hydrolyzes the ester bonds of the triglycerides. Lipase, as a digestive enzyme, is soluble in water but the triacylglycerides it hydrolyzes are not. Bile salts surround the fatty acid globules to make them more soluble. Lipase activity requires bile acids and its coenzyme to hydrolyze fast. Lipase is activated by the coenzyme colipase, which binds to the C-terminal non-catalytic domain. Upon binding, active lipase is stabilized for the hydrophobic interaction with the triacylglycerides ^[6]. Colipase must be present for activation of lipase when other amphiphilic molecules are present (such as phospholipids or bile salts). Colipase is also secreted in the pancreas, but in its inactive for which must be activated by trypsin before interacting with lipase ^[7]. Colipase and lipase are at opposite of the active site on the C-terminal, including polar interactions such as salt bridges (stars on the image) and van der waals forces which stabilize the interaction ^[8]. shows that the lid over the active sight is lifted and a 10 residue beta-5 loops changes confirmation exposing lipase's oxyanion hole and hydrophobic surface. Colipase hydrophobic loops interact with the hydrophobic atmosphere of the triacylglyceride initiating lipase active site binding to the lipid. Once bound, lipase initiates a serine-like hydrolysis involving His, Asp, Ser residues in the catalytic triad releasing the lipid products ^[9].

References

1. ↑ Voet, D.,etc. "Fundamentals of Biochemistry: Life at the Molecular Level" John Wiley and Sons, Inc: New Jersey, 2008.
2. ↑ Bourne, Y., etc. "Horse pancreatic lipase..."(1994) J.Mol.Biol. 238: 709-732 [1]
3. ↑ Fundamentals of Biochemistry...
4. ↑ Horse pancreatic lipase...
5. ↑ Fundamentals of Biochemistry...
6. ↑ Fundamentals of Biochemistry...
7. ↑ "Colipase". Wikipedia: The Free Encyclopedia. 5 July 2011 [2]
8. ↑ van Tilbeurgh H, etc."Structure of the pancreatic lipase-procolipase complex", 1992 Sep 10;359(6391):159-62. PMID:1522902.[3]
9. ↑ Fundamentals of Biochemistry...