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Lecture 32

PSL301H1 Lecture 32: L32 Digestion & Absorption
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Department
Physiology
Course
PSL301H1
Professor
Michelle French
Semester
Winter

Description
Lecture 32 Digestion and Absorption Silverthorn 7E: pp. 678-686 Friday, March 31 Lecture Outline I. Review composition of carbohydrates, protein, and fat. II. How and where are carbohydrates, proteins, and fats digested and absorbed? III. How are vitamins, minerals, and water absorbed? Recall: Functions of the Digestive System • Certain enzymes are released in inactive forms and then activated in the duodenum when it’s safe from autodigestion • Bicarbonate is also released to ensure that you can digest and absorb that material o All secretions are to aid in the digestive process • We’ll talk about how that material gets broken down into smaller units to get through the epithelial cells that line the GI tract into the lymphatic system and through the hepatic portal system There are various forms of transport into the GI tract. Types of Transport • Paracellular transport – between cells – tight junctions prevent this movement, but certain areas allow passage of some materials • Some disease states are characterized by the leakiness of this barrier • Transcellular transport – uptake of materials on apical surface of epithelial cells through specific transporters and channels that selectively allow material to enter the cell, transported across, and released through transporters or channels on basolateral surface of the cell (i.e., absorption of materials) – very selective • Transcytosis – materials too large for transporters or channels, so it’s brought in through endocytosis, vesicular transport across epithelial cells, and then exocytosis releases material on basolateral surface – involved in absorption of proteins and peptides Composition of carbohydrates, proteins, and fats. Carbohydrates • 50% of Western diets is carbohydrate – starches and sucrose • Long polysaccharides broken up using enzymes in mouth (amylase in saliva) • Get digested into various forms – disaccharides, which are digested by other enzymes (disaccharidases, specific to those forms) • Only as monosaccharides can carbohydrates be absorbed into the body • Have to be digested down into monosaccharides – glucose, galactose, and lactose Proteins • Proteins ingested in polypeptide forms and smaller peptides • Two classes of enzymes break proteins down depending on where they attack the peptide • Endopeptidases – break up peptides inside the polypeptide chains to make smaller peptides • Exopeptidases – lop of the ends of the polypeptide chains, at amino terminus or carboxyl terminus o Aminopeptidases (look different) and carboxypeptidases (more common) • Way of breaking proteins into smaller chains and then lopping amino acids off the ends Fats • 90% of lipids we ingest are triglycerides because most of the lipids in animal and plant products are triglycerides • We need to disassemble the triglycerides using enzymes (lipases) o Colipase is a helper product, not an active enzyme • Breaks triglyceride down into monoglycerides and free fatty acids – only in this form are they transported across epithelial barrier o Then reassembled to be absorbed, because there aren’t transporters to move large triglycerides across Carbohydrates: Mouth and Stomach • Salivary amylase breaks down starch into many different • Mouth: 5% of starch is broken down to maltose things – maltose, limit dextrin (short polysaccharides with • Stomach: 35% of starch broken down to maltose branches which can’t be broken down by amylase) o Digestion continues until amylase exposed to low pH • There is limited digestion in the mouth, so it depends on how long you keep the bolus in your mouth for the time that amylase has to interact with the carbohydrates • Digestion starts and continues in mouth as long it remains there, and once it hits the stomach, the pH will allow it to continue to digest (amylase stops when bolus in stomach) • Low pH in the stomach causes digestion due to amylases will stop – key to function in enzymes that have to work there Carbohydrates: Small Intestine • Nothing happens for carbohydrates in the stomach • Pancreatic amylase is more potent than salivary amylase • Pancreatic amylase is the same structure as salivary amylase, • Bicarbonate secretion important for activity of pancreatic amylase but more potent because the bolus has been broken up further in the stomach when it’s deposited into the small intestine, so it has greater access to the carbohydrates in that chyme • Pancreatic duct cells secrete bicarbonate (dumped into duodenum), key because the pH of material from the stomach is low, so when it passes into duodenum, enzymes there need a higher pH than what is delivered, so bicarbonate neutralizes it to bring pH back up for enzymes to function • Bicarbonate needs to be secreted into duodenum so pancreatic amylase can function in that area 2 Brush Border Enzymes Convert Small Carbohydrates to Monosaccharides • Enzymes that are anchored in microvilli in epithelium • Some brush border enzymes are important for breakdown of carbohydrates into monosaccharides • Specific enzymes act upon specific carbohydrates o Sucrose (disaccharide) broken down by sucrose o Limit dextrin broken down by dextrinase o Lactose broken down by lactase • Individuals who are lactose-intolerant are deficient in lactase activity, so lactose passes through small intestine into large intestine with bacteria, where they ingest and metabolize the lactose making gases and fatty acids o Gas – bacteria ingest and metabolize lactose producing gas and fatty acids – so individuals will experience gas o Cramps – release of gas pushes against large intestine causing muscle contraction in response to stretch o Osmotic diarrhea – metabolized fatty acids create osmotically active substances in lumen of large intestine which draws water back into the lumen from the body ▪ Osmotic diarrhea caused by presence of osmotically active substance in GI tract that draws water into large intestine • Transported across epithelial cells via transporters Carbohydrates: Absorption • SGLT1 moves glucose and Na into the cell from apical surface, + + depending on active transport of Na out on basolateral surface (Na - K -ATPase) o Galactose also uses SGLT1 to enter epithelial cell • Fructose enters on GLUT5 glucose transporter, facilitated transport • Each monosaccharide (glucose, galactose and fructose) move in at apical surface and leave on basolateral surface on GLUT2 • Monosaccharides move into interstitial space and into the capillary, and into the hepatic portal vein Protein Digestion Begins in the Stomach • Pepsinogen released from chief cells • Pepsinogen is inactive, secreted and then activated by acids in • Pepsin cleaves proteins at aromatic amino acids stomach and by pepsin itself, to break up polypeptide chain into o E.g., phenylalanine, tryptophan, tyrosine – peptides and amino acids endopeptidase • Pepsin is an endopeptidase that cleaves at specific amino acids to make smaller chains or individual amino acids 3 Protein Digestion: Small Intestine • Enteropeptidases help other peptidases become activated • Important to be anchored in brush border Details: Activation of Pancreatic Enzymes • Autodigestion prevented by zymogen • Brush border enzymes are embedded so they don’t get washed away in duodenum packaging, trypsin inhibitor synthesis, and • Acinar exocrine cells in pancreas – histologically, contain zymogens (granules) that trypsin autolysis contain inactive proteinases • Material from granules get deposited in pancreatic duct, released by sphincter of Oddi into lumen of duodenum • Zymogens contain many inactive enzymes (“ogen”) also trypsinogen (key proteinase activated by enzymes in brush border) • Once activated, trypsin itself is now activating all other inactive digestive enzymes which can now break down things like fats • If you have trypsinogen being made with all other enzymes in the pancreas, you want to make sure that it won’t become activated too early and this happens in a number of ways that acinar exocrine cells that ensure pancreas is safe from autodigestion by trypsin o Acinar cells make trypsin inhibitors in case trypsinogen becomes active in the acinar cells o Trypsin autolysis – digestion site in trypsin for trypsin; if it escapes the safety features in acinar cells, trypsin can inactivate itself o This is how key trypsin is key to activate all these enzymes Protein Digestion: Brush Border Enzymes • Enzymes that break up the proteins • Dipeptidase anchored in brush border which breaks down dipeptides • Aminopeptidases lop of amino acids from amino terminus, anchored in brush border o Theoretically, there aren’t as many aminopeptidase as carboxypeptidase • Breaking up proteins but you don’t have to digest proteins into individual subunits like you have to do for carbohydrates (into monosaccharides) • Can move peptides through as di- and tripeptides, as amino acids, and as small peptides (don’t have to be totally broken down into individual amino acids) 4 Protein: Absorption • Peptides broken down by enzymes • Di- and tripeptides enter at apical surface of epithelial cell on cotransporters that move amino acids along with H ions (PepT1 exchanger) • Activity of PepT1 is dependent on apical NHE to ensure that the H level is kept low inside epithelial cell so that it can be moved in o PepT1 requires that apical NHE activity • Di- and tripeptide inside cell as well as cotransport of AA with Na • Peptidases in epithelial cells break down di- and tripeptides into individual amino acids • Transport of amino acids out on sodium exchanger o Need activity of Na -K -ATPase to ensure low levels of Na to allow the transport in • Can also bring in small peptides through transcytosis and deposited into interstitium and blood (hepatic portal system) • This is how young babies take in maternal antibodies in breast milk because you can’t digest them – they’re transported via transcytosis Note: nucleic acids are digested by pancreatic and intestinal enzymes first into their component nucleotides and thein into nit
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