Lipase: Difference between revisions
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== '''Colipase Coenzyme''' == | == '''Colipase Coenzyme''' == | ||
Lipase is activated by the coenzyme colipase, which binds to the C-terminal non-catalytic domain of lipase. 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 and acts as a bridge between lipase and the lipid. Without colipase present, the accumulation of amphiphiles at the oil/water interface in the duodenum would prevent pancreatic lipase from binding. <ref>Crandall,W., Lowe, M. "Colipase Residues Glu64 and Arg65 Are Essential for Normal Lipase-mediated Fat Digestion in the Presence of Bile Salt Micelles" Journal of Biological Chemistry, 2001, (276) 12505-12512</ref>. Colipase is 10kDA protein, secreted by the pancreas in its inactive form, which must be activated by trypsin before interacting with lipase. Colipase is a small protein cofactor with 5 conserved disulfide bonds <ref>"Colipase". Wikipedia: The Free Encyclopedia. 5 July 2011 [http://en.wikipedia.org/wiki/Colipase]</ref>, and 2 surfaces- a hydrophilic surface (site of lipase C-terminal interaction) and a hydrophobic surface (contains multiple hydrophobic loops to bridge the lipid)<ref>"Colipase Residues..."</ref>. Colipase and lipase <scene name='Lipase/Contacts/1'>contacts</scene> are opposite of the active site on the C-terminal (contacts are regions of pink and yellow, with water molecules shown in darker blue). The enzymes are bound by polar interactions such as <scene name='Lipase/Salt_bridges/2'>salt bridges</scene>, <scene name='Lipase/Hphobic_interactions/1'>hydrophobic interactions</scene> and <scene name='Lipase/Hydrogen_bonds_non_water/1'>hydrogen bonds</scene> <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>. | Lipase is activated by the coenzyme colipase, which binds to the C-terminal non-catalytic domain of lipase. 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 and acts as a bridge between lipase and the lipid. Without colipase present, the accumulation of amphiphiles at the oil/water interface in the duodenum would prevent pancreatic lipase from binding. <ref>Crandall,W., Lowe, M. "Colipase Residues Glu64 and Arg65 Are Essential for Normal Lipase-mediated Fat Digestion in the Presence of Bile Salt Micelles" Journal of Biological Chemistry, 2001, (276) 12505-12512</ref>. Colipase is 10kDA protein, secreted by the pancreas in its inactive form, which must be activated by trypsin before interacting with lipase. Colipase is a small protein cofactor with 5 conserved disulfide bonds <ref>"Colipase". Wikipedia: The Free Encyclopedia. 5 July 2011 [http://en.wikipedia.org/wiki/Colipase]</ref>, and 2 surfaces- a hydrophilic surface (site of lipase C-terminal interaction) and a hydrophobic surface (contains multiple hydrophobic loops to bridge the lipid)<ref>"Colipase Residues..."</ref>. Colipase and lipase <scene name='Lipase/Contacts/1'>contacts</scene> are opposite of the active site on the C-terminal (contacts are regions of pink and yellow, with water molecules shown in darker blue). The enzymes are bound by polar interactions such as <scene name='Lipase/Salt_bridges/2'>salt bridges</scene>, <scene name='Lipase/Hphobic_interactions/1'>hydrophobic interactions</scene> and <scene name='Lipase/Hydrogen_bonds_non_water/1'>hydrogen bonds</scene> <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>. | ||
In the presence of colipase, the enzyme is activated which moves the <scene name='lipase/N-terminal_flap/1'>N-terminal flap</scene> (shown in red) which is composed of amino acids 216-239. The N-terminal flap moves in a concerted fashion along with the C-terminal domain to reveal the active site (green), allowing it to bind with a substrate. It is hypothesized that this flexibility may have significance in binding the colipase-lipase complex with the water-lipid interface.<ref>http://www.pdb.org/pdb/explore/explore.do?structureId=1ETH</ref> The reorganization of the flap also induces a second conformational change that creates the oxyanion hole.<ref>http://www.nature.com/nature/journal/v362/n6423/abs/362814a0.html</ref> | |||
[[Image:M0218.stg01.gif|200px|left|thumb|Lipase Mechanism Reaction 1]] | [[Image:M0218.stg01.gif|200px|left|thumb|Lipase Mechanism Reaction 1]] | ||
