Lipase: Difference between revisions

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 and a surface change occurs on lipase.  Colipase's 4 hydrophobic loops interact with the hydrophobic atmosphere of the triacylglyceride initiating the lipase active site binding to the lipid, and lid opening to reveal a more hydrophobic environment for the triacylglycerol.  Although a diverse array of lipase enzymes are found in nature, occupying diverse protein scaffolds, most are built upon an alpha/beta hydrolase fold<ref>PMID: 1678899</ref><ref>PMID:1409539 </ref>  and possess a [[chymotrypsin]]-like <scene name='Lipase/Catalytic_site_outerview/1'>catalytic triad </scene>comprised of an acidic residue, a histidine, and a serine nucleophile. In the case of the images above of a horse pancreatic lipase, the catalytic triad is comprised of <scene name='Lipase/Catalytic_triad/4'>Ser 152, Asp 176 and His 263. </scene><ref>PMID:8182745</ref>.  This catalytic triad functions like most found in nature, first with the Aspartic acid forming a hydrogen bond with His 263, increasing the pKa of the histidine imidazole nitrogen. This allows the histidine to act as a powerful general base and deprotonate the serine. The deprotonated serine then can serve as a nucleophile and attack the ester carbonyl of one of the fatty acids on the 1 or 3 carbons of the glycerol backbone of the lipid substrate.  Upon attacking the lipid, a negatively charged tetrahedral intermediate is formed (Reaction 1).  It is stabilized in the oxyanion hole by two residues:  <scene name='Lipase/Catalytic_triad_with_oxyanion/2'>Phe 77 and Leu 153</scene>.