1. PANCREATIC LIPASE PEER FATHIMA BARAKATHU INDIA

2. Pancreatic Lipase Pancreatic lipase, also known as pancreatictriacylglycerol lipase, is secreted from the pancreas, and is the primary lipase (enzyme) that hydrolyzes (breaks down) dietary fat molecules in the human digestive system, converting triglyceride substrates found in ingested oils to monoglycerides and free fatty acids by breaking hydrogen bonds. 3. Pancreatic Lipase Lipase requires a high pH for its activation among food enzymes. That is why fats are the hardest of all foods to digest. Triacylglycerol + 2 H2O2-monoacylglycerol + 2 fatty acid anions 4. Mechanism Bile salts secreted from the liver andstored in gallbladder are released into the duodenum where they coat and emulsify large fat droplets into smaller droplets, thus increasing the overall surface area of the fat, which allows the lipase to break apart the fat more effectively 5. Mechanism The resulting monomers (2 freefatty acids and one 2monoacylglycerol) are then moved by way of peristalsis along the small intestine to be absorbed into the lymphatic system by a specialized vessel called a lacteal. 6. Mechanism The resulting fatty acids andmonoacylglycerols are incorporated into bile saltphospholipid micelles. These micelles are absorbed into the brush border of the small intestine and eventually enter the bloodstream as chylomicrons. 7. Pancreatic Lipase Cleaves acylglycerols mainly to FA and2-monoacylglycerols Requires solubilization of the substrate Also requires colipase (secreted by the pancreas) that anchors and activates the enzyme Absorption of resulting FA and monoAG requires bile salts micelles 8. Hydrolysis of cholesterol esters By pancreatic cholesterol esterase The free cholesterol is transported inthe bile acid micelles and absorbed through the brush border Here, it is reacylated with acyl-CoA 9. Hydrolysis of triglycerides 10. Reaction 11. Pancreatic Lipase Unlike some pancreatic enzymes that are activated by proteolytic cleavage (e.g. trypsinogen), pancreatic lipase is secreted in its final form. However it onlybecomes efficient in the presence of colipase in the duodenum in the presence of bile acids provided by the liver. In humans, pancreatic lipase is encoded by the PNLIP gene. 12. Structure of Pancreatic Lipase 13. Cartoon diagram of Human Pancreatic Lipase secondarystructure: alpha helices in red, beta sheets in yellow, and random coil in green in complex with pigcolipase (colored blue) and a small molecule inhibitor (upper left). 14. Structure A computergenerated image of a type of pancreatic lipase (PLRP2) from the guinea pig. 15. Biochemical properties Pancreatic lipase is a water-soluble lipolyticenzyme that hydrolyse ester linkages of triglycerides The enzyme is a single-chain glycoprotein of 449 amino acids. Structural results suggest that Ser 152 is the nucleophilic residue essential for catalysis forms part of an Asp-His-Ser triad that is chemically analogous to, but structurally different from, that of the serine proteases 16. Inhibition of pancreatic lipase activity Natural products that inhibit the activityof pancreatic lipase may suppress dietary fat absorption from the small intestine. Potential candidates include basic peptides and proteins, which destroy the lipid emulsion by binding to bile salts, thus suppressing the activity of pancreatic lipase. 17. Inhibition Recently, protamine, purothioninand histone, which belong to a class of basic proteins, were reported to inhibit lipase . These substances inhibit lipase in substrates containing phosphatidylcholine. From these results, it was suggested that these compounds inhibit lipase activity by interaction with trioleinphosphatidylcholine 18. Pancreatic Lipase People who are concerned withlosing weight may be more than familiar with this enzyme and what it does. Thats because several dieting products have surfaced that boast the ability to block its activity in order to inhibit the absorption of fats. 19. Pancreatic Lipase In fact, orlistat is a prescriptionmedication that prevents up to 30% of dietary fats, including triglycerides, from being absorbed through the intestines. This results in a reduction in total calorie intake and, subsequently, weight loss. 20. Research on Lipases Researchers have learned about a fewother unique properties of pancreatic lipase by studying hibernating squirrels. While this enzyme is normally found in the intestines, it is found in great concentration in the hearts of these animals, but only from late fall until early spring. 21. Research on Lipase Apparently, after completing the job ofdigesting dietary fats for storage during the big sleep, the enzyme takes up residence in the heart to help it function while body temperature and oxygen levels dramatically decline. What is particularly interesting about this is that most other enzymes are rendered inactive below certain temperatures, while this one retains about 30% of its activity. 22. Hyper production Excessive production of this enzyme may indicate the presence of certain disorders, most notably: inflammation of the pancreas, or pancreatitis. bowel obstruction, peptic ulcers, or kidney disease, and are also a temporary side effect of some medications, like morphine and codeine. 23. Hypo production- Deficiency Diminished levels may suggest that Some cells of the pancreas areirreversibly damaged. Pancreatic lipase monitoring is also used to help diagnose Crohn's disease, Cystic fibrosis, and Celiac disease. 24. Deficiency Lipase deficient people can be expectedto have a tendency towards high cholesterol, high triglycerides, Difficulty losing weight and Diabetes, or A tendency towards glucosuria (sugar in the urine without symptoms of diabetes), which can lead to Heart disease. 25. Lipase deficiency Because lipase requires the co-enzyme chloride, lipase deficient people have a tendency towards hyphochlorhydria (low chlorides in our electrolyte balance). 26. Lipase deficiency Lipase deficient people have decreased cellpermeability, meaning nutrients cannot get in and the waste cannot get out of the cell. For example, diabetics are lipase deficient and cannot get glucose into their cells, and wastes or unwanted substances cannot get out. People with "hidden viruses" that are often diagnosed with "Chronic Fatigue Syndrome" also fall into this category. Lipase modulates cell permeability so that nutrients can enter and wastes can exit. 27. Lipase deficiency A common symptom of lipase deficiencyis muscle spasms. This is not the "muscle cramp" (tetany) resulting from low ionized blood calcium. It commonly occurs as trigger point pain in the muscles across the upper shoulders, but it can occur in other muscles, such as those in the neck or anywhere in the small or large intestines including the muscles of the rectal tissues. 28. Lipase deficiency People with "spastic colon" may belipase deficient. They are given toxic muscle relaxant drugs to control the symptoms 29. Lipase deficiency The condition of vertigo, orlabrynthis, also called Meniere's Disease (dizziness aggravated by movement such as walking or driving), can result from lipase deficiency. 30. Lipase deficiency A nutritionist saw this condition developsuddenly in a young man after the typical American fat challenge test--a meal which consisted of a fried fish sandwich with tartar sauce, double cheeseburger plus a bag of french fries. The dizziness was accompanied by severe nausea and vomiting which was aggravated by movement. This condition lasted several days. Lipase can relieve a condition like this, often within minutes. 31. Lipase deficiency The condition of menopause isoften associated with lipase deficiency because lipase addresses the gonadal tissue. 32. Thank you