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Cell Bio 8- Small Intestine Phase I • • • • • Function of Small Intestine Mix intestinal content to ensure proper assimilation Assimilation of nutrients • Digestion • Absorption Regulate the emptying of chyme from the stomach Regulate pancreatic secretions Continue the movement of unabsorbed digested material through the alimentary tract Functional Anatomy • Segmentation • Ensures proper mixing • Maximizes exposure to digestive enzymes • Maximizes exposure to intestinal mucosa • Structure • Maximize the intestinal mucosa surface area • Circular folds X 3 • Villi X 30 • Small finger-like projections of the mucosal surface • Microvilli X 600 • Cover each epithelial cell (enterocyte) • Enterocytes rapidly turn over every 2-3 days Digestion • Chemical breakdown of foodstuff • Three types • Luminal • Intraluminal enzymes • Salivary, stomach and pancreatic enzymes • Membrane • Brush border enzymes • Intracellular • Intracellular peptidases • Note: Intracellular digestion doesn’t occur for all nutrients. Lipid are reconstructed intracellularly Absorption • • • Stomach • Limited digestion and absorption Small intestine • Primary area for absorption of most nutrients • Principally occurs in the duodenum and jejunum Colon • Very little nutrient absorption • Absorption of water and electrolytes Hydrolysis Hydro “water” lysis “separation” • The cleavage of a chemical bond by the addition of water • All three major nutrients undergo hydrolysis during digestion • Proteins • Long-chain amino acids joined together by peptide bonds between carboxyl and amino groups • Hydrolysis breaks down proteins into shorter peptide chains and individual amino acids Cell Bio 8- Small Intestine Phase I • • • • • Carbohydrates • Oligosaccharides and polysaccharides are broken down to monosaccharides • Only monosaccharides are absorbed by the small intestine Lipids • Triglycerides • 3 free fatty acid molecules on a glycerol backbone • Hydrolysis separates the fatty acid molecules from the glycerol Carbohydrates Starch • Polymers of glucose • Amylose--Straight-chain polymers • Amylopectin--Branched-chain polymers Disaccharides • Sucrose (table sugar)--Glucose + fructose • Lactose-- Glucose + galactose Fiber • Plant derived carbohydrate polymers and lignin • Cannot be digested by humans enzymes • Digested by colonic bacteria Starch Digestion • Phase I – Amylase digestion • Starts with salivary amylase (ptyalin) • Non-essential • Pancreatic amylase • Most significant • Hydrolyze internal α-1,4 bonds only • Incomplete digestion • Results in glucose oligomers • Maltose (dimer) • Maltotriose (trimer) • α-limit dextrins • Phase II – Brush border digestion Brush Border Digestion • Disaccharide and oligosaccharide digestion • Occurs on the surface of intestinal epithelial cells • By membrane bound glycosylated carbohydrate hydrolases • Hydrolyze to monomers • Carbohydrates can only be absorb as monosaccharides Cell Bio 8- Small Intestine Phase I Carbohydrate Hydrolase Regulation • Heavily glycosylated to protect them from pancreatic proteases • Degraded between meals and must be resynthesized • Sucrase, isomaltase and glucoamylase are produced in excess • Assimilation of monosaccharides is limited by luminal transporters Lactose Intolerance • Lactase expression diminishes after weaning • Natural developmental decline in lactase expression • More common in AA’s, Asians and Hispanics • More common in individuals without consistent lactose in their diet • Lactose assimilation is limited by lactase digestion • Lactose remains in the intestinal lumen • Retention of water • Abdominal cramping, gas and diarrhea Carbohydrate Absorption • Only monosaccharides are absorbed • Luminal transport • Sodium/glucose transporter 1 (SGLT1) • Glucose • Galactose • Against their concentration gradient • Glucose/fructose transporter 5 (GLUT5) • Fructose • Not coupled to Na+ • Inefficient and can be saturated with excessive sugar intake • GLUT5 expression can increase with increased fructose consumption • Fructose absorption highest when combined with glucose 1:1 ratio • Basolateral transport • Glucose transporter 2 (GLUT2) • Glucose • Galactose • Fructose • GLUT5 • Fructose • GLUT2 is most important Carbohydrate Assimilation Disorders • Mutation in the SGLT1 gene • Rare • Inability or decreased absorption of glucose and galactose • Depends on the mutation • Results in luminal retention of glucose and symptoms similar to lactose intolerance • Diarrhea • Abdominal cramping Cell Bio 8- Small Intestine Phase I • • • • Proteins Complex polymers composed of amino acids • 20+ different amino acids • Dietary proteins contain 9 essential amino acids • Cannot be synthesized de novo Complete proteins • Contain all of the essential amino acids • Ex. Fish, poultry and eggs Incomplete proteins • Do not contain all of the essential amino acids • Vegetables and grains • Vegetarians must eat a variety of vegetables and soy protein Source of allergens • Gluten in wheat • Casein in milk • Multiple proteins in peanuts and seafood Protein Digestion Proteins must be broken down to amino acids, dipeptides and tripeptides to be absorbed • 4 steps • Acid + 3 enzymatic processes • Stomach 1. Acid hydrolysis 2. Pepsin • Small intestine 1. Pancreatic proteases 2. Brush border peptidases • Step 1 • Acid in the stomach can hydrolyze proteins into large peptides • Step 2 • Pepsin catalyzed hydrolysis of proteins 1. Pepsinogen is released by chief cells of oxyntic glands 2. Pepsinogen is autocatalytically activated to pepsin at low pH • Pepsin cleaves at proteins at neutral amino acids 1. Prefers aromatic and large aliphatic chains 2. Incomplete digestion of protein • Leaves some intact proteins, mostly large peptides and few amino acids Cell Bio 8- Small Intestine Phase I • Step 3 • Pancreatic proteases 1. Inactivate proenzymes released by the pancreas are activated by a 2 step process Endopeptidase • Cleave proteins only at internal bonds • Do not release individual amino acids Trypsin • Specific for basic amino acids • Leaves a C-terminus basic amino acid Chymotrypsin and Elastases • Specific for neutral amino acids • Leaves a C-terminus neutral amino acid Exopeptidases • Cleave single amino acids form the end of a peptide chain Carboxypeptidase A • Specific for C-terminus neutral amino acids Carboxypeptidase B • Specific for C-terminus basic amino acids So, what’s left? Neutral and basic amino acids Short peptides with C-terminus acidic amino acids • Step 4 • Brush border digestion • Membrane bound exopeptidases including aminopeptidases and carboxypeptidases • Further digest oligopeptides to absorbable amino acids, dipeptides and tripeptides • Note: Some peptides just don’t go away. Peptides with proline and glycine are difficult to digest Cell Bio 8- Small Intestine Phase I Protein Absorption • Dipeptides and tripeptides absorbed more efficiently than individual amino acids • Luminal transport • 6 different known amino acid transporters in the small intestines • Typically non-specific • Some specificity for neutrality and charge but still overlap • Peptide transporter 1 (PepT1) • Dipeptides and tripeptides • H+ cotransporter • Uptake peptidomimetic drugs • Basolateral transport • Peptides taken up by the enterocytes are digested by cytosolic peptidases • Amino acids are transported into the plasma and lymphatic system • Note: Whole proteins are rarely absorbed. Human babies have a short and limited ability to absorb immunoglobulins from nursery. Protein Assimilation Disorders • Amino acid absorption disorders • Don’t typically have a clinical effect on absorption • Large redundancy in amino acid transporters • Amino acids can be taken up as dipeptides and tripeptides • Effect other organ systems • Hartnup disease • Defective transport of neutral amino acids • Decreased absorption and reabsorption of tryptophan from the intestine and kidney respectively • Tryptophan is required for NAD synthesis • Cysteinuria • Defective transport of basic acids • Impaired reabsorption of cysteine from the urine can lead to kidney stones