Sandbox 51: Difference between revisions
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In addition to the effects of bile salts, 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 <ref>Fundamentals of Biochemistry...</ref>. Colipase must be present for activation of lipase. Lipase activation at the lipid-water interface of triacylglycerides, in the presence of colipase and bile salts, is known as interfacial activation. Colipase is also secreted in the pancreas, but in its inactive form, which must be activated by trypsin before interacting with lipase <ref>"Colipase". Wikipedia: The Free Encyclopedia. 5 July 2011 [http://en.wikipedia.org/wiki/Colipase]</ref>. Colipase and lipase <scene name='Sandbox_51/Contacts/3'>contacts</scene> are at opposite of the active site on the C-terminal, including polar interactions such as <scene name='Sandbox_51/Salt_bridges/2'>salt bridges</scene> and van der waals forces which stabilize the interaction <ref>van Tilbeurgh H, etc."Structure of the pancreatic lipase-procolipase complex", 1992 Sep 10;359(6391):159-62. PMID:1522902.[http://www.proteopedia.org/wiki/index.php/1n8s]</ref>. <scene name='Sandbox_51/Lipase_and_colipase/1'>Colipase and lipase in complex with a triacylglyceride</scene> 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. Before colipase binding, the beta-5 loop serves to protect the oxyanion hole from solvent interaction 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 <ref>Fundamentals of Biochemistry...</ref>. | In addition to the effects of bile salts, 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 <ref>Fundamentals of Biochemistry...</ref>. Colipase must be present for activation of lipase. Lipase activation at the lipid-water interface of triacylglycerides, in the presence of colipase and bile salts, is known as interfacial activation. Colipase is also secreted in the pancreas, but in its inactive form, which must be activated by trypsin before interacting with lipase <ref>"Colipase". Wikipedia: The Free Encyclopedia. 5 July 2011 [http://en.wikipedia.org/wiki/Colipase]</ref>. Colipase and lipase <scene name='Sandbox_51/Contacts/3'>contacts</scene> are at opposite of the active site on the C-terminal, including polar interactions such as <scene name='Sandbox_51/Salt_bridges/2'>salt bridges</scene> and van der waals forces which stabilize the interaction <ref>van Tilbeurgh H, etc."Structure of the pancreatic lipase-procolipase complex", 1992 Sep 10;359(6391):159-62. PMID:1522902.[http://www.proteopedia.org/wiki/index.php/1n8s]</ref>. <scene name='Sandbox_51/Lipase_and_colipase/1'>Colipase and lipase in complex with a triacylglyceride</scene> 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. Before colipase binding, the beta-5 loop serves to protect the oxyanion hole from solvent interaction 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 <ref>Fundamentals of Biochemistry...</ref>. | ||
==Inhibition== | ==Inhibition== | ||
The inhibition of pancreatic lipase has serious effects on storage and absorption of fats taken in by the body. Inhibition of the enzyme reduces the amount of fat stored and absorbed by the body, and is therefore a potentially strong basis for pharmaceuticals to combat obesity. Because lipase is a part of the serine esterase family, it is inhibited in a similar manner. One such compound is a <scene name='Sandbox_51/Inhibitor/ | The inhibition of pancreatic lipase has serious effects on storage and absorption of fats taken in by the body. Inhibition of the enzyme reduces the amount of fat stored and absorbed by the body, and is therefore a potentially strong basis for pharmaceuticals to combat obesity. Because lipase is a part of the serine esterase family, it is inhibited in a similar manner. One such compound is a <scene name='Sandbox_51/Inhibitor/2'>C11 alkyl phosphonate</scene> inhibitor (shown interacting with the lipase-coplipase structure). The inhibitor acts by binding Ser 152 in the active site inducing confirmational changes in the beta-5 loop structures. The alkyl chain fits into the hydrophobic portion of the active lipase-colipase complex mimicking the fatty acid produced through hydrolysis in the normal enzymatic reaction <ref>Egloff, M.P., etc. "The 2.46 angstroms resolution structure of the pancreatic lipase colipase complex inhibited by a C11 alkyl phosphonate."(1995) J. Biochemistry 34: 2751-2762 [http://www.pdb.org/pdb/explore/explore.do?structureId=1lpb]</ref>. | ||
==References== | ==References== | ||
<references /> | <references /> | ||
