Lipase: Difference between revisions

Lipase is a hydrolase that catalyzes the breakdown of lipids by hydrolyzing the esters of fatty acids.  This makes lipase important in digestion and promoting absorption of fats in the intestines.  Lipase is primarily found in and secreted by the pancreas but is also found in the saliva and the stomach.  Pancreatic lipase (PDB ID:  1HPL) which is pictured to the right is a carboxylic ester hydrolase.  It is also commonly called pancreatic triacylglycerol lipase and its enzyme class number is E.C. 3.1.1.3 <ref name="1HPL PDB SUM">[http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?pdbcode=1hpl&template=main.html] 1HPL PDB SUM </ref>.  The reaction catalyzed by this enzyme is shown below.   

Further breakdown ultimately results in 2-monoacylglycerols and free fatty acids <ref name= "A cross-linked complex between horse pancreatic lipase and colipase">[http://www.sciencedirect.com/science/article/pii/0014579389815923] A cross-linked complex between horse pancreatic lipase and colipase</ref>. An in depth discussion of the mechanism can be found in the Lipase Catalytic Mechanism section. The determination of the structure and function of lipase was a gradual process.  Lipase activity was first demonstrated in the pancreas by Claude Bernard in 1846.  It wasn't until 1955 that Mattson and Beck demonstrated a high-specificity of pancreatic lipase for triglyceride primary esters <ref name= "History of Lipids">[http://www.cyberlipid.org/history/history1.htm] History of Lipids</ref>.  In recent years, determination of the crystal structure of pancreatic lipase has become the focus and many scientists have worked to further this.  See also [[Molecular Playground/Pancreatic Lipase]].

Pancreatic lipase is a 50 kDa protein, consisting of two identical, 449 residue chains <ref name= "1HPL PDB">[http://www.pdb.org/pdb/explore/explore.do?structureId=1HPL] 1HPL PDB</ref>. The <scene name='Lipase/Secondary_structures/1'>secondary structure</scene>s of lipase (in one subunit) include 102 residues which create 13 alpha helices, shown in red, and 139 residues involved in beta sheets totaling 28 strands, shown in gold. The alpha helices account for 22% of the protein, while the beta sheets comprise 30%.  Each chain contains two well defined <scene name='Lipase/N_and_c_terminus/1'>domains</scene>. The N terminal domain, shown in blue, is characterized by an alpha/beta hydrolase fold.  While the C terminal domain, shown in green,  contains a beta sheet sandwich which interacts with colipase <ref>http://www.pdb.org/pdb/explore/explore.do?structureId=1HPL</ref>.  Each monomer and dimer structure of lipase is held together by disulfide bonds, hydrogen bonds, and electrostatic interactions (salt bridges).  Lipase has 12 total <scene name='Lipase/Disulfide_bonds/2'>disulfide bonds</scene> between cysteine residues.  <scene name='Lipase/Salt_bridges/1'>Salt bridges</scene> are formed between the positively charge nitrogens (blue) in Arg and Lys, and negative oxygens (red) in Asp and Glu residues.  <scene name='Lipase/Hydrogen_bonds/2'>Hydrogen bonds</scene> (in yellow) also stabilize the enzyme between main chain and side chain atoms.  Lipase has a distinct distribution of <scene name='Lipase/Hphobic_residues/3'>hydrophobic and hydrophilic</scene> residues (purple spacefill represents polar residues).  Hydrophobic collapse contributes to much of the secondary and tertiary structures, as the <scene name='Lipase/Surface/1'>hydrophobic core residues</scene> (shown in white) make up the interior of the protein while polar residues (transparent blue) are on the surface <ref>http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=1HPL</ref>.  In addition, lipase has two <scene name='Lipase/Lipase_ligand/1'>calcium ligands</scene>, one buried in each monomer subunit.  The image shows the green calcium ion in subunit A, coordinated by Glu187, Arg190, Asp192, and Asp195.  The Ca(+2) charge is stabilized by negatively charged glutamate and aspartate residues, and the oxygen atoms from two water molecules (pink).  The calcium ion is essential to protein folding and enzyme activity <ref>http://www.springerlink.com/content/g5h1613440115701/fulltext.pdf</ref>.