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AHS 2013 Digestion and Metabolism 2 Sarah Harney 2. Digestion & Absorption • How are water and ions absorbed? • How are the main nutrient groups - carbohydrates, proteins, fats – digested and absorbed? • What happens in disorders of digestion/absorption? – lactose intolerance and coeliac disease Reading: Stanfield, pp 580-589 1 Digestion & Absorption of Nutrients GENERAL PRINCIPLES • Breakdown of complex molecules – Enzymes (pH) • Absorption into gut cells Mechanisms of absorption: • Passive -not energy-dependent Diffusion Facilitated diffusion –carrier mediated • Active - requires energy Carrier-mediated Primary active transport – transporter protein directly hydrolyses ATP for energy Secondary active transport – couples energy released from movement of one substance to co-transport another 2 1 AHS 2013 Digestion and Metabolism 2 Sarah Harney Bulk flow of liquid in gut • Input – Ingestion ~ 2 litres per day – Secretion (gut) ~ 7 litres/day • Output – Faeces ~100 ml/day • Conclude ~ 9 litres/day absorbed 3 Absorption of Water • • Passive Driven by an osmotic gradient across mucosal epithelium – Due to Na+ [actively pumped from gut lumen into lateral spaces] • Water can move either through the epithelial cells (transcellular) or through the ‘tight junctions’ H 2O (paracellular) Na+ ~95% absorption in small intestine Na+ • Absorptive cell 4 2 AHS 2013 Digestion and Metabolism 2 Sarah Harney Carbohydrate (CHO) Digestion Amylase digestion of carbohydrates produces the disaccharide maltose or short polysaccharides known as limit dextrins Starch (polysaccharide) 5 Carbohydrate digestion and Absorption • Carbohydrates are initially digested by amylases • Further digestion occurs at the brush border / microvilli on intestinal epithelial (absorptive) cells 6 3 AHS 2013 Digestion and Metabolism 2 Sarah Harney Carbohydrate (CHO) Digestion of microvilli Disaccharides are further digested to monosaccharides by brush border enzymes 7 Digestion of Carbohydrates to Disaccharides is done by brush border enzymes • CHOs must be monosaccharides to be absorbed • Brush border enzymes hydrolyse disaccharides to monosaccharides Dextrins Sucrose Lactose Maltose Dextrinase Sucrase Lactase Maltase Glucose Glucose + Fructose Glucose + Galactose Glucose X 2 8 4 AHS 2013 Digestion and Metabolism 2 Sarah Harney CHO Digestion — Summary • Polysaccharides to disaccharides (gut amylases) • Disaccharides to monosaccharides (brush border) – Glucose, galactose enter gut cells by energy-dependent secondary active transport • i.e. ‘piggy-back on Na+ gradient (active) – Fructose enters gut cells by facilitated diffusion (passive) 9 CHO Absorption into GI Epithelial Cells Glucose + galactose are co-transported with Na+ across apical membrane Fructose absorbed by facilitated diffusion Glucose molecules cross basolateral membrane by facilitated diffusion and diffuse into capillaries 10 5 AHS 2013 Digestion and Metabolism 2 Sarah Harney CHO Absorption into Bloodstream • Glucose, galactose enter capillaries down concentration gradient • Fructose enters capillaries via passive carrier-mediated transport 11 Lactose Intolerance • Lactose intolerance is due to deficient production of lactase • Lactase normally hydrolyses lactose (sugar present in milk) to glucose and galactose • Insufficient lactase means lactose is not digested and absorbed in the small intestine • Digestion of lactose by bacteria in colon results in production of gas and other bi-products leading to bloating and diarrhoea • Incidence ~5 % in northern Europe, up to 90 % in Asian populations 12 6 AHS 2013 Digestion and Metabolism 2 Sarah Harney Protein Digestion Essentially similar to CHO • Proteins converted to peptides • Protein digestion begins in stomach with gastric pepsinogen • Pepsinogen is activated by HCl to form active pepsin 13 Protein Digestion • Protein digestion is continued in small intestine by pancreatic enzymes • Proenzymes (zymogens) secreted by the pancreas are converted to active forms following activation of trypsin by a brush border enzyme, enterokinase Precursor Trypsinogen Chymotrypsinogen Procarboxypeptidase Active form Trypsin Chymotrypsin Carboxypeptidase 14 7 AHS 2013 Digestion and Metabolism 2 Sarah Harney Peptidase activation • Pancreatic trypsinogen • Activated by enterokinase • Trypsin then activates other zymogens 15 Protein absorption similar to CHO • Peptides broken down to amino acids (brush border) • Amino acids are actively transported by carriers into gut epithelial cells • Amino acids then transported across basolateral membrane by facilitated diffusion and diffuse into capillaries 16 8 AHS 2013 Digestion and Metabolism 2 Sarah Harney Digestion and Absorption of Fat • Most ingested fats are triglycerides • They are broken down to monoglycerides and free fatty acids for absorption • Digestion of fat is done by lipases secreted in the mouth and stomach but mostly by pancreatic lipases in small intestine 17 Digestion of Fat • Hydrophobic fat globules are broken up into smaller droplets or emulsified by bile salts • Bile salts contain polar –OH and –COOH groups that are hydrophilic 18 9 AHS 2013 Digestion and Metabolism 2 Sarah Harney Digestion of Fat • Bile salts + lecithin aggregates called micelles •As fats are absorbed by epithelial cells, micelles release more fatty acids and monoglycerides for absorption 19 Micelles deliver fats to the absorptive cells • Bile salts, lecithin and cholesterol aggregate to form micelles with a hydrophilic outside and hydrophobic lipid inside • Fats can be carried through the water based intestinal fluids dissolved in the lipid core 20 10 AHS 2013 Digestion and Metabolism 2 Sarah Harney Absorption of Fat • Monoglycerides and FFA enter cells by diffusion • Once absorbed they are reassembled as triglycerides • They are then complexed with proteins in Golgi apparatus to form lipoproteins known as chylomicrons • Chylomicrons are secreted by exocytosis into the interstitial fluid and from there enter the lymphatic vessels 21 Summary of Fat Digestion & Absorption • Fat to triglycerides (pancreatic lipase) • Bile salts emulsify (surface area) • Bile salts — micelles containing monoglycerides and free fatty acids (FFA) • Enter passively (fat-soluble) • Triglyceride synthesis — chylomicrons • Exocytosis and entry into lacteals 22 11 AHS 2013 Digestion and Metabolism 2 Sarah Harney Coeliac Disease • An autoimmune disease, high incidence in Ireland, up to 1 in 100 •Intolerance to gluten –a protein present in wheat and other grains such as rye, barley, oats • Ingestion of gluten triggers an immune response, resulting in inflammation of the intestinal mucosa • Autoimmune response results in damage to intestinal villi causing malabsorption From: www.uhbristol.nhs.uk Endoscopy Coeliac • Reduced absorption leads to bloating, diarrhoea and vitamin deficiencies • Disease is managed by following a glutenfree diet 23 12