Digestion of Dietary Lipids

Objectives of the Lecture Understanding the overall process of dietary lipids digestion, the organs involved, the enzymes required and the end products. Recognizing the biochemical explanation for the clinical manifestations of diseases that involve defective lipids digestion and/or absorption

Digestion of Dietary Lipids Adult ingestion of lipids per day is about 60-150 grams Components of dietary lipids: 90% Triacylglycerol (TAG) 10% Phospholipids (PL) Cholesterol (C) Cholesterol esters (CE) Free fatty acids (FFA) with fat soluble vitamins Stages of Digestion of Dietary Lipids 1- In mouth (limited) 2- In stomach 3- In small intestine : Emulsification of lipids (by bile acids & peristalsis) Degradation of lipids by pancreatic enzymes

Digestion of lipids In the Mouth & Stomach Lingual lipase: secreted by glands at the back of the tongue. Gastric lipase: secreted by gastric mucosa Both enzymes are relatively stable of pH 4-6 (so they are called acid lipases) Their primary target is triacylglycerol (TAG) containing less than 12 carbon fatty acids i.e. short or medium chain length fatty acids (found in milk fat) These two enzymes are particularly important in: - Neonates whose milk fat is the primary source of calories Patients with pancreatic insufficiency as in cystic fibrosis (with absence of pancreatic lipase)

Emulsification of Dietary Lipids in the Small Intestine Emulsification increase of the surface area of the hydrophobic lipid droplets so that the digestive enzymes can act effectively Emulsification is performed by two complementary mechanisms: 1- Detergent property of bile salts 2- Mechanical mixing due to peristalsis Bile salts are made in the liver & stored in the gall bladder Bile salts interact with the dietary lipid & the aqueous duodenal contents thus stabilizing the particles & preventing them from coalescing

Bile salts are made in the liver & stored in the gall bladder Bile salts interact with the dietary lipid & the aqueous duodenal contents thus stabilizing the particles & preventing them from coalescing

Degradation of Dietary Lipids by Pancreatic Enzymes The dietary lipids are enzymically degraded by pancreatic enzymes , whose secretion is hormonally controlled

Triacylglycerol (TAG) Degradation Pancreatic lipase is found in high concentration in pancreatic secretion Acts on TAG by removing fatty acids at carbon 1 & 3 forming 2-monoacylglycerol & two FAs Only severe pancreatic deficiency as cystic fibrosis results in maldigestion malabsorption of fat Colipase Secreted in 1:1 ratio, as zymogen [ procolipase] by pancreas activated in intestine by trypsin Anchors the lipase at lipid aqueous interface Orlistat an antiobesity drug , inhibits gastric & pancreatic lipases causing decreased fat digestion & hence absorption resulting in weight loss

Phospholipid (PL) Degradation PL are degraded at the position 2 by pancreatic phospholipase A2 releasing a free fatty acid & lysophospholipid. Phospholipase A2 is secreted as proenzyme, activated by trypsin & requires bile salts for optimum activity This is followed by removal of fatty acids at position 1 of lysophospholipid by the action of lysophospholipase leaving glycerylphosphoryl base

Cholesteryl Ester (CE) Degradation 15-20% of dietary cholesterol is esterified Cholesterol ester hydrolase (cholesterol esterase) activity is greatly increased in the presence of bile salts

Overview of Digestion of Dietary Lipids Mouth CE Stomach PL Small Intestine TAG Primary products of lipids digestion 2- monoacylglycerol Free FA Free cholesterol

Absorption of Lipids by Intestinal Mucosal Cells In the jejunum, the primary products of lipids digestion (2- monoacylglycerol , Free FA & Free cholesterol ) together with bile salts form mixed micelles then absorbed at the brush border membrane Mixed micelles are disc shaped clusters of amphipathic lipids that coalesce with their hydrophilic groups on the outside of the cluster & their hydrophobic groups on the inside Short & medium chain length fatty acids do not require mixed micelles for absorption So, considered for dietary therapy for individuals with malabsorption of other lipids.

Resynthesis of TAG, CE & PL inside intestinal cells Long-chain fatty acids entering enterocytes are used to form TAG, PL & CE Short & medium –chain fatty acids are not converted to their CoA derivative & are not re-esterified to 2-monoacylglycerol They are released directly into the portal circulation by serum albumin

Formation of Chylomicrons inside intestinal cells Inside intestinal mucosal cells: Newly synthesized triacylglycerol (TAG) & cholesterol esters (CE) are very hydrophobic & therefore are packaged as lipid droplets surrounded by a thin layer of phospholipids (PL), free cholesterol (C) & a protein molecule (apolipoprotein B-48 or apo B-48) forming the chylomicrons. The outer layer (apo B-48) stabilizes the particle & prevents it from coalescing Chylomicrons are released by exocytosis from villi of intestine into the lacteals to the thoracic duct of the lymphatic system to left subclavian vein to blood Lacteals: are lymphatic vessels originating in villi of small intestine

Use of Dietary Lipids by the Tissues (Chylomicron Metabolism) Type I Hyperlipoproteinemia

Lipid Malabsorption Lipid malabsorption result in increased lipids in the feces (steatorrhea) Steatorrhea can be caused by disturbances of: 1- Lipid digestion 2- Lipid absorption 3- Both Liver causes: Def. of bile acids production Obstruction of CBD Pancreatic causes: as: cystic fibrosis Intestinal causes as: infection