Sandbox 47: Difference between revisions

Pancreatic <scene name='Sandbox_47/Lipase/1'>lipase</scene> (EC 3.1.1.3) is an esterase enzyme that catalyzes the break down of lipids in the digestive system. It is secreted from the pancreas and converts triglyceride substrates to monoglycerides and free fatty acids by ester hydrolysis. <ref>"Pancreatic lipase". Wikipedia: The Free Encyclopedia. 7 Nov 2011 [http://en.wikipedia.org/wiki/Pancreatic_lipase]</ref> Pancreatic triglyceride lipase is critical for the efficient absorption of dietary fats.<ref>"Colipase". Wikipedia: The Free Encyclopedia. 5 July 2011 [http://en.wikipedia.org/wiki/Colipase]</ref>

Unlike many proteases, pancreatic lipase is secreted in its final form. However, it is only active in the presence of <scene name='Sandbox_47/Colipase/1'>colipase</scene> in the duodenum. Colipase is a 90-residue protein that forms a 1:1 <scene name='Sandbox_47/Colipasecontacts/2'>complex with lipase</scene>. <ref>Voet D, Voet JG, Pratt CW. "Fundamentals of Biochemistry: Life at the Molecular Level" John Wiley and Sons, Inc: New Jersey, 2008..</ref> <ref>"van Tilbeurgh H, Sarda L, Verger R, Cambillau C. 1992. Structure of the pancreatic lipase-procolipase complex. Nature 359: 159-162. </ref> Colipase is also secreted in the pancreas, but in its inactive form, procolipase, which is activated by trypsin in the intestinal lumen. Colipase prevents the inhibitory effect of bile salts on the lipase-catalyzed intraduodenal hydrolysis of dietary long-chain triglycerides. Colipase binds to the C-terminal, non-catalytic domain of lipase, which stabilizes the active conformation and increases the hydrophobicity of the binding site. <ref>"Colipase". Wikipedia: The Free Encyclopedia. 5 July 2011 [http://en.wikipedia.org/wiki/Colipase]</ref> In other words, colipase activates the enzyme through the movement of the N-terminal domain loop or lid. Here, lipase and colipase can be seen <scene name='Sandbox_47/Lipasecolipasesubstrate/1'>in complex with a triacylglycerol</scene>. <ref>Hermoso J, Pignol D, Kerfelec B, Crenon I, Chapus C, Fontecilla-Camps JC. 1996. Lipase activation by nonionic detergents. J. Biol. Chem. 271: 18007-18016.</ref>

The mechanism of pancreatic lipase begins with His263 deprotonating Ser152, which attacks the carboxy carbon of the triacylglycerol substrate in a nucleophilic addition. In the second step, the oxyanion collapses, initiating an elimination of the diacylglycerol product, which deprotonates His263 and acylated Ser152. Next, His263 deprotonates water, which attacks the carboxyl carbon of the acylated Ser152 in a nucleophilic addition. Finally, the oxyanion collapses, initiating an elimination of the carboxylate product, and Ser152, which deprotonates His263. <ref>"Overview for MACiE Entry M0218". EMBL-EBI. 17 June 2008. [http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/MACiE/entry/getPage.pl?id=M0218]</ref>

Pancreatic lipase is secreted into the duodenum through the duct system of the pancreas. In a healthy individual, it is in very low concentration in serum. Under extreme disruption of pancreatic function, such as pancreatitis or pancreatic cancer, the pancreas may begin to digest itself and release pancreatic enzymes including pancreatic lipase into serum. Measurement of serum concentration of pancreatic lipase can therefore aid in diagnosis of acute pancreatitis. <ref>"Pancreatic lipase". Wikipedia: The Free Encyclopedia. 7 Nov 2011 [http://en.wikipedia.org/wiki/Pancreatic_lipase]</ref>