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NME2.12: LIPID DIGESTION AND ABSORPTION 01/02/08 LEARNING OUTCOMES Describe the digestion and absorption of lipids Lipids are fats (or fat-like substances) that can be either non-polar and completely water insoluble or polar and partially water soluble Dietary lipids consist mainly of triglycerides and phospholipids Lipids are absorbed entirely within the small intestine, mostly in the duodenum Solid fat and oil masses are first emulsified by gastric churning with various digestive enzymes to form 1μm semi-soluble droplets which increase the area of the oil-water interface The emulsion droplets are coated in various substances including bile salts, phospholipids and cholesterol to stabilise them forming a surface monomolecular layer o Triglycerides and cholesteryl esters make up the emulsion droplet core The droplets then reach the duodenum, triggering the release of CCK to stimulate bile and pancreatic enzyme secretion Pancreatic lipase in conjunction with co-lipase (which ‘shields’ lipase from the bile salts) acts at the oilwater interface to break down the fat droplets o Parts of the emulsion droplet bud away as multilamellar vesicles consisting of several lipid bilayers o Bile salts transform them into unilamellar vesicles with only a single lipid bi-layer o Bile salts degrade these further to finally form mixed micelles (i.e. lipids and bile salts) with a lipid mono-layer Mixed micelles contain 2-monoglycerides, free fatty acids and bile salts o They can also contain fat-soluble vitamins (A, D, E, K) o The micelles can then be absorbed into the enterocytes (rate-limiting step) The intestinal lumen is centrally alkaline but on its borders harbours an acidic microclimate called the disequilibrium zone (‘unstirred water layer’) o This acts as a diffusion barrier to large macro-aggregates allowing only monomers and mixed micelles to diffuse efficiently o Once mixed micelles reach the apical membrane they shed their lipid monomers (due to acidic climate) Absorptive enterocytes allow uptake of free fatty acids, glycerol, cholesterol and monoglycerides Describe the re-esterification of fatty acids and transport to blood Short- and medium-chain fatty acids are bound to albumin and exocytosed directly into the portal circulation Long-chain fatty acids are re-esterified into triglycerides, phospholipids and cholesteryl esters in the smooth ER o This maintains the diffusion gradient from the intestinal lumen Together with apoproteins from the rough ER, the fat components form nascent chylomicrons and VLDL o Chylomicrons are the largest lipoprotein particles in the blood (mostly triglycerides) o o o They are then exported into the lymph system via lacteal lymphatic capillaries Fat-soluble vitamins often follow this pathway Lymph lacteals lead to the thoracic duct and enter circulation through the left subclavian vein LIPID MALABSORPTION Common indication of fat mal-absorption is steatorrhoea Pancreatic deficiencies reduce available pancreatic lipase Bile acid deficiencies inhibit micelle formation, caused by: o Liver disease o Biliary obstruction o Bacterial overgrowth o Ileal disease / resection Chylomicron formation deficiencies can arise e.g. from abetalipoproteinaemia (can be treated with vitamin E) Lymphatic deficiencies e.g. o Congenital lymphangiectasis (dilatation of lymphatic vessels) o Whipple’s disease (stunted intestinal villi, bacterial infection – treated with antibiotics)