Sandbox 43

Please do NOT make changes to this Sandbox. Sandboxes 30-60 are reserved for use by Biochemistry 410 & 412 at Messiah College taught by Dr. Hannah Tims during Fall 2012 and Spring 2013. Pancreatic Lipase Introduction <StructureSection load='1hpl' size='500' side='right' caption='Structure of Horse Pancreatic Lipase (PDB entry 1hpl)' scene=>A subclass of esterases, pancreatic lipase (EC 3.1.1.3) is an enzyme that catalyzes the hydrolysis and formation of lipids. While produced in the pancreas, it is also present in the stomach and mouth. Due to its effective ester bond hydrolysis of lipids, lipase is essential for fat digestion, breaking lipids into monoglycerides and single fatty acids. If one is lipase deficient, it is hard to obtain adequate nutrition from food. This results in diseases such as cystic fibrosis, Crohn's disease, and celiac disease. Furthermore, this deficiency can also lead to high cholesterol and difficulty losing weight as the body breaks down fats at a much slower rat. Structure The quaternary structure of horse pancreatic lipase (as featured right) contains two molecules which each contain 449 amino acid residues, 705 water molecules, and 1 calcium ion. These two identical molecules are connected by a two-fold symmetry axis. The interactions between the a chain and the b chain include hydrogen bonds and salt bridges. The secondary structure of lipase is composed of 102 residues that constitute 13 alpha helices (22% helical) and 139 residues that constitute 28 beta sheet strands (30% beta sheets). Lipase is essentially composed of two domains, the N-terminal domain, which contains the active site of lipase (consisting of three residues: Ser-152, Asp-176, and His-263). The N-terminal domain also contains the lid region (residues 216-239) which serves to block the active site, which is nestled in the hydrophobic regions, from the solvent. Additionally, the C-terminal domain is essential to the binding of lipase with colipase, an important cofactor for the catalysis of lipids. This forms the lipase-colipase complex. Calcium Ligand The most prominent ligand involved in the structure of lipase is the calcium ion. This ion has been shown to promote the folding of lipase into its active dimer state. As such, the calcium ion is extremely important in forming the lipase-fat complex, necessary for the breakdown of lipids. Studies have shown that an increase in calcium concentration in a lipase catalyzed reaction resulted in an increase in the rate of the reaction. Colipase Cofactor Colipase is a small protein that is necessary for efficient lipid catalysis by lipase. It is secreted by the pancreas in its inactive form as procolipase which is converted into the active colipase by trypsin. It binds to the non-catalytic C-terminal domain of lipase and in so doing stabilizes its active conformation as it hydrolyzes lipids. Furthermore, it also binds to the lipid interface, increasing the affinity between lipase and the lipid. Mechanism File:Hydrolysis.gif General mechanism of papain catalysis. Arg-175, which orients His 159, and Gln-19, which contributes to the formation of the oxyanion hole, are not shown.