Introduction

Pancreatic (EC 3.1.1.3) is an esterase enzyme that catalyzes the break down of lipids in the digestive system. It is secreted from the pancreas. It converts triglyceride substrates to monoglycerides and free fatty acids by ester hydrolysis. ^[1]

Structure

Horse pancreatic lipase (PDB ID 1hpl) consists of 449 amino acids and 705 well-defined water molecules in two subunits, and . The two chains interact through a variety of . Lipase also binds two as ligands through a variety of . Its consists of 22% and 30% . It contains both and . The overall molecular structure of horse lipase has two well-defined domains. The N-terminal domain contains the and has a typical alpha/beta hydrolase fold topology.The active site contains a catalytic triad that closely resembles that in serine proteases. The C-terminal domain, for colipase binding, has a beta-sheet sandwich topology.^[2]

Function

Most lipases act at a specific position on the glycerol backbone of the lipid substrate.^[3] Pancreatic lipase catalyzes the hydrolysis of triacylglycerols at their 1 and 3 positions to form 1,2-diacylglycerols and 2-acylglycerols together with the Na+ and K+ salts of fatty acids. The enzymatic activity of pancreatic lipase increases when it contacts the lipid-water interface. Binding to the lipid-water interface requries mixed micelles of phosphatidylcholine and bile acids as well as colipase. Unlike many proteases, pancreatic lipase is secreted in its final form. However, it is only active in the presence of in the duodenum. Colipase is a 90-residue protein that forms a 1:1 ^{[4] [5]} Colipase is also secreted in the pancreas, but in its inactive form, procolipase, which is activated by trypsin in the intestinal lumen. Colipase prevents the inhibitory effect of bile salts on the lipase-catalyzed intraduodenal hydrolysis of dietary long-chain triglycerides.^[6]

Clinical Significance

Pancreatic lipase is secreted into the duodenum through the duct system of the pancreas. In a healthy individual, its concentration in serum is very low. Under extreme disruption of pancreatic function, such as pancreatitis or pancreatic cancer, the pancreas may begin to digest itself and release pancreatic enzymes including pancreatic lipase into serum. Measurement of serum concentration of pancreatic lipase can therefore aid in diagnosis of acute pancreatitis. ^[7]

References

1. ↑ "Pancreatic lipase". Wikipedia: The Free Encyclopedia. 7 Nov 2011 [1]
2. ↑ Bourne Y, Martinez C, Kerfelec B, Lombardo D, Chapus C, Cambillau C. 1994. Horse pancreatic lipase. J. mol Biol. 238: 709-732.
3. ↑ "Lipase". Wikipedia: The Free Encyclopedia. 6 Nov 2011 [2]
4. ↑ Voet D, Voet JG, Pratt CW. "Fundamentals of Biochemistry: Life at the Molecular Level" John Wiley and Sons, Inc: New Jersey, 2008..
5. ↑ "van Tilbeurgh H, Sarda L, Verger R, Cambillau C. 1992. Structure of the pancreatic lipase-procolipase complex. Nature 359: 159-162.
6. ↑ "Colipase". Wikipedia: The Free Encyclopedia. 5 July 2011 [3]
7. ↑ "Pancreatic lipase". Wikipedia: The Free Encyclopedia. 7 Nov 2011 [4]