Lipid metabolism Digestion and absorption of Lipids

Digestion of lipids Little or no digestion occurs in the mouth or stomach since: – No significant amount of lipase is present in the secretion of mouth or stomach – No mechanism for emulsification of lipid exists – The acid pH of gastric secretion is not helpful to lipid digestion The major site of lipid digestion is the small intestine, where dietary lipid undergoes its major digestive processes using enzymes secreted by pancreas

Digestion of lipids (cont’d) Digestion in small intestine – The acidic stomach contents called chyme, containing dietary fat leaves the stomach and enters small intestine – Which stimulates the secretion secretin and cholecystokinin acts on the gallbladder, causing it to contract and release bile into the small intestine Acts on the exocrine cells of the pancreas, causing them to release digestive enzymes containing lipase Decrease gastric motility, resulting in a slower release of the gastric contents into the small intestine

Digestion of lipids (cont’d) – Secretin cause the pancreas to release a solution enriched in bicarbonate that helps neutralize the pH of the acidic chyme and changes the pH to the alkaline side, which is necessary for the activity of pancreatic and intestinal enzymes – Pancreatic juice and bile enter the upper small intestine, the duodenum, by way of the pancreatic and bile ducts

Digestion of lipids (cont’d) – The major function of bile is to provide the emulsifying agents: The bile salts Phosphotidylcholine – Both these are powerful emulsifying agents. They emulsify the triacylglycerols into small droplets – Three lipid digestive enzymes secreted by pancreas are: Pancreatic lipase Cholesterol esterase Phospholipase-A 2

Action of pancreatic enzymes on dietary lipids in the small intestine Hydrolysis of dietary triacylglycerols TAG Emulsified triacylglycerols are readily attacked by pancreatic lipase  Lipase hydrolyses fatty acid in the 1 and 3 positions of the triacylglycerol, producing 2 monoacylglycerols and two molecules of fatty acids  Slow subsequent isomerization of the 2 monoacylglycerol to 1 or 3 monoacylglycerols occurs and hydrolyzed to glycerol and a third molecule of fatty acid

Action of pancreatic enzymes on dietary lipids in the small intestine Hydrolysis of dietary phospholipids PL Dietary glycerophospholipids are digested by pancreatic phospholipase-A 2  This enzyme catalyzes the hydrolysis of fatty acid at the 2- position of the glycerophospholipids, leaving lysophospholipids which being detergent, aid emulsification and digestion of lipids  The lysophospholipids either enter the mucosal cells or are degraded further by e lysophospholipids enzyme secreted by intestinal cells, which catalyzes the removal of the remaining fatty acid residue

Action of pancreatic enzymes on dietary lipids in the small intestine Hydrolysis of cholesterol ester CE Cholesterol esters are hydrolyzed by pancreatic cholesterol ester hydrolyase (cholesterol esterase), which produce cholesterol plus free fatty acid

Products of lipid digestion Free fatty acids, free cholesterol, 2-monoacylglycerol, small amount of 1-monoacylglycerol and lysophospholipid are the primary products of dietary lipid digestion. These together with bile salts, form mixed micelles – Micelles are of very much smaller dimension than emulsion globules – Fat soluble vitamins A, D, E and K are also packaged in these micelles and are absorbed from micelles along with the primary products of dietary lipid digestion

Absorption of lipids by intestinal mucosal cells The mixed micelles approach the brush border membrane of the intestinal mucosal cells There the lipid components from mixed micelles pass through and are absorbed into mucosal cells of the jejunum and ileum by diffusion The net result is the transfer of monoacylglycerol, fatty acids, cholesterol, and lysophospholipid molecules into the cell Short and medium chain triacylglycerols can be absorbed as such are then hydrolyzed by an intestinal lipase Short and medium chain fatty acids do not require bile salts for their absorption. They are absorbed directly into intestinal epithelial cell. Because they do not need to be packaged into chylomicrons, they enter the portal blood rather than lymph and are transported to the liver bound to serum albumin.

Absorption of lipids by intestinal mucosal cells (cont’d)

After absorption within the intestinal wall, the following events occur – 1-monoacylglycerols are further hydrolyzed to produce free glycerol and fatty acids by an intestinal lipase (glycerol ester hydrolase) – 2-monoacylglycerols are reconverted to triacyglycerols the fatty acids required for this synthesis can arise from three sources; Absorbed from the lumen Produced by hydrolysis of absorbed monoacylglycerols Synthesized in the mucosal cells

Absorption of lipids by intestinal mucosal cells (cont’d) The utilization of fatty acids for resynthesis of, triacyglycerols first requires their conversion to active form acyl-CoA by the action of acyl-CoA synthetase (thiokinase) The absorbed lysophospholipids and cholesterol are also reacylated with acyl-CoA to regenerate PL and CE The free glycerol released in the intestinal lumen is not reutilized but passes directly to the portal vein. However, the glycerol-3-phosphate, formed within the intestinal cells by the glucose, can be reutilized for triacylglycerol synthesis.

Transport Triacylglycerol, phospholipid, cholesterol esters synthesized in the intestinal mucosa and absorbed fat soluble vitamins are transported from the mucosal cells into the lymph in the form of lipoprotein known as chylomicrons because they are insoluble in water

Transport (Cont’d) Chylomicrons are composed of: – Triacylglycerols (85 to 90%) – Cholesterol and cholesterol ester (5%) – Phospholipids (7%) – Protein (apolipoprotein B (2%) Although the amounts of protein and phospholipid in chylomicrons are small, they are essential for the transport of fat from the mucosal cells and if their synthesis The chylomicrons pass from lymph into the blood through the thoratic duct. After a fatty meal, the plasma is milky in appearance due to the presence of these particles

Lipid malabsorption Lipid malabsorption results in a loss of lipid as much as 30g/day including the fat soluble vitamins and essential fatty acids in the faeces Conditions in which the faeces contain large amounts of fat and fatty acids are called steatorrhea caused by number of conditions The most common causes are: – Bile salt deficiency occurs in liver disease or due to obstruction in the bile duct – Pancreatic enzyme deficiency – Defective chylomicrone synthesis