3. LIPIDS Lecture 3

LIPID DIGESTION Dietary lipids are: triglycerides, phospholipids, steroids, especially cholesterol and cholesterol esters, fat-soluble vitamins “vitamin A, D, E and K”, and carotenoids. Lipid digestion begins in the mouth, continues in the stomach, and ends in the small intestine. Enzymes involved in triacylglycerol digestion are called LIPASE. Lipases are proteins that catalyze the partial hydrolysis of triglycerides into a mixture of free fatty acids and acylglycerols. There are several lipases, the most important of which is produced by the pancreas “pancreatic lipase”, the others are lingual lipase, gastric lipase, and breast milk lipase. Other enzymes involved in lipid digestion are: cholesterol esterase and phospholipases A1 and A2.

Digestion in mouth “lingual lipase” Lingual lipase is produced and secreted by serous lingual glands, Active at low pH ”Optimum pH: 4.0-4.5” It is released into the mouth along with the saliva, catalyzes the first reaction in the digestion of dietary lipid, In the mouth, dietary fat is broken into small particles and mixed with lingual lipase. The ideal substrate in fat is short chain saturated fatty acid >>> Short chain FAs are released as end products of digestion, which are absorbed directly from stomach wall and enters portal vein Its enzymatic action continues in stomach.

Digestion in mouth “lingual lipase” Lingual lipase activity is not particularly important for healthy adults. On the contrary, it is very important for infants, in which pancreatic lipase is still immature, also advantaged by the fact that milk triglycerides are rich in short- chain and medium-chain fatty acids. Lingual lipase is present since 34th week of gestation in the baby. When there is absence of pancreatic lipase due to pancreatic disease, lingual lipase replaces it and fulfills its function of fat digestion>>> Lingual lipase remains active even in low pH.

II. Digestion in stomach “gastric lipase” Gastric lipase is secreted by the chief cells of the gastric mucosa, The enzyme preferentially catalyzes the hydrolysis of triglycerides with short-chain and medium-chain fatty acids. More effective at alkalin media (average pH 7.8) Regardless of the type of fatty acids, gastric lipase preferentially cleaves those at the sn*-3 position, leading to the release of a free fatty acid and a 1,2-diacylglycerol. In spite of limitations, lingual lipase and gastric lipase account for about 30% of total fat digestion. They both play important role in lipid digestion in neonates as milk is the main source of their energy. These lipases are also very important for fat digestion in patients with pancreatic insufficiency (e.g. cystic fibrosis) with near /complete absence of pancreatic lipases.  sn*: stereospecific numbering.

III. Digestion in Small intestine Small intestine is the major site of fat digestion. Effective digestion due to presence of bile salts (via emulsification) and pancreatic enzymes Bile salts “” act as effective emulsifying agents for fat. EMULSIFICATION OF LIPIDS IN DUODENUM: Emulsification process is the breaking up of fat globules in to much smaller emulsion droplets. This process increases the surface area of fat/oil, so that digestive enzymes can act effectively. Mechanisms of action includes two complementary mechanisms: i. Reduction of surface tension of fat droplets by emulsifying agents such as bile salts (cholesterol derivative; synthesized & secreted by the liver). ii. Mechanical mixing by gut peristalsis “contraction and relaxing”. https://www.youtube.com/watch?v=LpjNKN3sIqA

III. Digestion in Small intestine 2. ACTION OF PANCREATIC enzymes: Secretion of pancreatic juice is stimulated by: Passage of acidic gastric contents in to the duodenum By secretion of secretin & Cholecystokinin (CCK). (digestive hormones released when food from the stomach reaches the first part of the small intestine (duodenum). content of pancreatic juice: i. Pancreatic lipase: for the digestion of triglycerides It removes FA from C1 & C3 of glycerol and produces 2-MAG (2- monoglyceride) & 2 FFA. 2-MAG represent 70% of total end product FA & glycerol together represent 30% of total end product. MAG is then hydrolyzed to glycerol & FFA (action of pancreatic lipase)

III. Digestion in Small intestine 2. ACTION OF PANCREATIC ENZYMES : content of pancreatic juice: i. Pancreatic lipase:…… ii. Phospholipase A2: for the digestion of phospholipids (PL) it removes FA from C2 of glycerol moiety and produce lysoPL. iii. Cholesterol esterase: for the digestion of cholesteryl ester

LIPID ABSORPTION Products of lipid digestion: Mostly are : Glycerol, FFA and MAG In addition to: Phospholipid and cholesteryl ester What is absorption?? It is the passage of ions, fluids and small molecules into blood or lymph via the epithelial lining of the GI lumen

LIPID ABSORPTION Glycerol and short fatty acids (less than 12 carbon) pass directly through the intestinal cells (enterocytes) into the bloodstream and travel with a carrier protein to the liver for further processing. Monoglycerides and long chain fatty acids (> 14 carbon) will associate with bile salts and phospholipids to form micelles.

LIPID ABSORPTION What are micelles?? Micelles are disk shaped clusters of amphipathic lipids that combine with their hydrophobic groups on the inside and their hydrophilic groups on the outside of clusters. Mixed micelles are soluble in the aqueous environment of the intestinal lumen. The micelles approach the brush border membrane of the enterocytes. 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. Micelles are constantly breaking down and re-forming, feeding a small pool of monoglycerides and fatty acids that are in solution. sz

LIPID ABSORPTION 3. Once inside the enterocyte, monoglycerides and fatty acids are re-synthesized into TAG. 4. The TAG, along with cholesterol and fat soluble vitamins, combine with proteins inside the golgi body to form chylomicrons. What are chylomicrons?? Chylomicrons are lipoproteins, special particles that are designed for the transport of lipids in the circulation. Chylomicrons are released by exocytosis at the basolateral surface of the enterocytes. Chylmicrons are too large to enter typical capillaries, therefore they enter lacteals, lymphatic capillaries. Chylomicrons then flow into the circulation via lymphatic vessels.

LIPID ABSORPTION 5. Chylomicrons deliver absorbed TAG to the bodys cells. TAG in chylomicrons and other lipoproteins are hydrolyzed by lipoprotein lipase, an enzyme that is found in capillary endothelial cells. Monoglycerides and fatty acids released from chylomicrons then diffuse into cells.