Lipid Digestion and Absorption Lecture PDF

Clinical biochemistry / second stage Lipid Digestion and Absorption Digestion is the chemical breakdown of large food molecules into smaller molecules that can be used by cells. The breakdown occurs when certain specific enzymes are mixed with the food. The major lipids in the diet are triacylglyce...

Clinical biochemistry / second stage Lipid Digestion and Absorption Digestion is the chemical breakdown of large food molecules into smaller molecules that can be used by cells. The breakdown occurs when certain specific enzymes are mixed with the food. The major lipids in the diet are triacylglycerols and, to a lesser extent, phospholipids. These are hydrophobic molecules and must be hydrolyzed and emulsified to very small droplets (micelles) before they can be absorbed. The fat-soluble vitamins – A, D, E, and K – and a variety of other lipids (including cholesterol) are absorbed dissolved in the lipid micelles. Absorption of the fat soluble vitamins is impaired on a very low fat diet. Hydrolysis of triacylglycerols is initiated by lingual and gastric lipases that attack the sn-3 ester bond, forming 1,2-diacylglycerols and free fatty acids, aiding emulsification. Pancreatic lipase is secreted into the small intestine and requires a further pancreatic protein, colipase, for activity. It is specific for the primary ester links – ie, positions 1 and 3 in triacylglycerols – resulting in 2-monoacylglycerols and free fatty acids as the major end-products of luminal triacylglycerol digestion. Monoacylglycerols are hydrolyzed with difficulty to glycerol and free fatty acids, so that less than 25% of ingested triacylglycerol is completely hydrolyzed to glycerol and fatty acids. Digestion is greatly aided by emulsification, the breaking up of fat globules into much smaller emulsion droplets. Bile salts and phospholipids are amphipathic molecules that are present in the bile. Motility in the small intestine breaks fat globules apart into small droplets that are coated with bile salts and phospholipids, preventing the emulsion droplets from re-associating. The emulsion droplets are where digestion occurs. Emulsification greatly increases the surface area where water-soluble lipase can work to digest TAG. Another factor that helps is colipase, an amphipathic protein that binds and anchors lipase at the surface of the emulsion droplet. 1 Clinical biochemistry / second stage Hormones Involved in Digestion 1-Secretin: Secretin is produced by cells of the duodenum It stimulates the pancreas to produce sodium bicarbonate, which neutralizes the acidic chyme. It also stimulates the liver to secrete bile. 2-CCK (cholecystokinin): CCK production is stimulated by the presence of food in the duodenum. It stimulates the gallbladder to release bile and the pancreas to produce pancreatic enzymes. Micelles After digestion, monoglycerides and fatty acids associate with bile salts and phopholipids to form micelles. Micelles are about 200 times smaller than emulsion droplets (4-7nm versus 1µm for emulsion droplets). Micelles are necessary because they transport the poorly soluble monoglycerides and fatty acids to the surface of the enterocyte where they can be absorbed. As well, micelles contain fat soluble vitamins and cholesterol. The figure at right illustrates that micelles are small enough to fall between the microvilli. 2 Clinical biochemistry / second stage Mixed micelle formed by bile salts, triacylglycerols and pancreatic lipase Micelles are constantly breaking down and re-forming, feeding a small pool of monoglycerides and fatty acids that are in solution. Only freely dissolved monoglycerides and fatty acids can be absorbed, NOT the micelles. Because of their nonpolar nature, monoglycerides and fatty acids can just diffuse across the plasma membrane of the enterocyte. Some absorption may be facilitated by specific transport 3 Clinical biochemistry / second stage Digestion of lipids: hydrolysis Triglycerides (TG) hydrolyzed by *pancreatic lipase TG + H2O → diglyceride + fatty acid (FA) diglyceride + H2O → monoglyceride (MG) + FA *Phospholipase A1 and A2 Hydrolyzes fatty acids from phospholipids *Cholesterol esterase Hydrolyzes fatty acids from cholesterol esters cholesterol esters & phospholipids* (PL) ↓ esterase ↓ phospholipases FA + cholesterol (chol) FA + lysoPL 4  Clinical biochemistry / second stage Pancreatic Colipase Secreted from pancreas as procolipase Activated (cleaved) by trypsin Anchors lipase to the micelle One colipase to one lipase (i.e., 1:1 ratio) Absorption - Lipids Fatty acids, 2-monoglycerides, cholesterol, and cholesterol esters move down concentration gradient (passive diffusion) repackaged in intestinal cell for transport to liver.newly formed triglycerides accumulate as ‘lipid 5  Clinical biochemistry / second stage droplets’ at the endoplasmic reticulum, coated with a protein layer These protein-coated lipid droplets are called chylomicrons Chylomicrons absorbed from enterocytes into lacteals (lymph vessel Ultimately enter blood via thoracic duct most long chain fatty acids absorbed into lymphatic system Blood lipids transported as lipoproteins Overview of Fatty Acid Uptake Short- and medium-chain fatty acids Enter portal blood directly from enterocyte Bound to albumin in blood in Albumin–FFA complex Oxidized in liver or elongated and used for triglyceride formation Long- chain fatty acids Form chylomicron Drain into the lymphatics via the lacteal in mammals Enter bloodstream at the thoracic duct Stabilizes lipids for transport in lymph and blood (aqueous environment Glycerol and short chain fatty acids directly enter mesenteric blood 6