System Physiology Lecture 10 April 21 Key messages from Dietary guidelines for Americans, 2005 Consume a variety of foods while staying within energy needs Control intake of calories to manage body weight Be physically active every day Increase daily intake of fruits and vegetables, whole grains, and non-fat or low-fat milk and milk products If you drink alcoholic beverages do so in moderation Sites of the GIT absorption of nutrients Carbohydrages, proteins and lipids -Most absorbed in the early duodenum -Jejunum -Ileum Calcium, Iron and Folate -Most absorbed in the early part of the duodenum -Calcium has an absorption capacity down to the late ileum. Bile Acids -Body has a difficult time absorbing and digesting fat without bile acids/salts. -Recirculated into the terminal portions of the small intestine and the ascending colon. -Most reabsorbed in the ileum. -Enterohepatic circulation of bile. -A particular bile salt can be recirculated up to 3 times during the digestion of a single meal. Vitamin B 12 (Cobalamin) -Absorbed exclusively in the ileum. -Problems with Cobalimin problems with maintenance of RBC count. -Cobalimin is a cofactor along with another one called intrinsic factor in erythropoesis. General patterns of digestion and absorption About 5 patterns that the mammalian gut uses: No digestion -Simplest form of digestion -Involves a single molecule of glucose Lumenal hydrolysis of a polymer to a monomer -Occurs somewhere in the small intestine -A small protein (pentapeptide) -Hydrolyzed by protein proteases and converted to a bunch of amino acids (5) -Transported across mucosal wall and into circulation as individual AAs. Brush-border (mucosal) hydrolysis of polymer to monomer -Doesn’t occur in the small intestine -A mucosal epithelial cell in the small intestine has an enzyme -Table sugar, a disaccharide (sucrose -The bond between the glucose -and fructose is hydrolyzed by the enzyme -Transported into the circulation. Intracellular (cytosolic) hydrolysis -A small peptide (tripeptide) is absorbed intact into the enterosite -Once inside, it comes in contact with a protease and is broken down into amino acids. Luminal hydrolysis followed by intracellular resynthesis -Triglyceride (backbone glycerol molecule attached to a fatty acid chain) -Broken down into its components, transported across the membrane and recombined in the cytosol. Carbohydrates, brief description Starch (plant polysaccharide, 45-60% CHO diet) Amyolse (straight chains of α -1,4 linkages) Individual glucose monomers attached by the linkages. Amylopectin (branched, macromolecule, α -1, 4- and α -1, 6-linkages) Disaccharides (30 – 40% CHO diet) Sucrose (table sugar) Lactose (milk sugar) Dietary fiber (cellulose, lignins, pectins) Soluble (fruits, vegetables) Insoluble (wheat, lentils, beans, related food products) -Contain more α-1,6 linkages than α -1, 4 -Not available for digestion by luminal amylases. -More of these fibers get into the colon. They retain water in the colon because they bind ions (ions are usually hydrated). This helps prevent colon cancer. α -1,4 and α-1,6 carbon (glucose) bonds defined Where a new branch develops off the polymer, there are α-1,6 linkages. Luminal mammalian enzymes cannot break these bonds. Effects of GIT luminal α -amylase on complex carbohydrates Amylase can cleave a complex carbohydrate into: Maltose (disaccharide) Maltotriose (trisaccharide) α -Limit dextrins (contain 1,6 linkages that amylase can’t break) Mucosa brush border carbohydrate enzymes Brush Border Carbohydrate Hydrolases Digestion of carbohydrates to monosaccharides Digestion of starch in the lumen Digestion of amylase by α-amylase Maltose Maltotriose Digestion of amylopectin by α-amyase Maltose Maltotriose α -Limit dextrins Amylase cannot break the terminal bonds in the molecule next to the 1,6 linkage. Brush Border Enzymes Lactase Sucrose is piggybacked on isomaltase Break down α-Limit dextrins and maltotriose Glucoamylase Glucose and galactose use a sodium symporter (SGLT1 – sodium glucose transporter 1) to be absorbed into the cell. Circulation Effects of lactose intolerance (lactase deficiency) on plasma level of glu/lact and H2 in expired air Presence of lactase activity Plasma glucose on y axis, hours on x axis Lactose and glucose curves are the same -Blood glucose rises after ingestion, then back to a steady state within a 3-4 hour period of time. -Several hours later, volumes of expired air are collected and the hydrogen gas is measured. Due to the colonic bacteria that can further digest the glucose and convert it to H2, how much H2 should be in the breath of a healthy person can be quantified. Lactase deficiency Glucose curve is higher first, then lower than lactose curve. -Huge production of H2 measured in the breath. Summary of carbohydrate digestion/absorption (assimilation) -Begins with amylases in mouth and stomach -Continues in duodenal lumen and at duodenal brush border -Co-transported with Na+ across apical membrane (SGLT-1) -Other apical transporters for fructose (e.g. GLUT5) -Basolateral uptake by GLUT2 (GLUT5 for fructose?); driven by Na+/K+-ATase at basolateral membrane -Main source of calories in diets of westerners. Amylase in lumen of gut Names of enzymes that are part of the brush border system (sucrose, lactose, α limit dextrins) Protein digestion and absorption in the mammalian GIT More complex than for carbohydrates Four phases (stomach, duodenum, brush border, enterocyte) Central role for pancreatic proteases Dietary roles of essential vs non-essential amino acids Fate of dietary protein as it exits the stomach and enters the duodenum 4 classes of proteins produced by the pancreas: Amylase for carbohydrates Lipase for fats/lipids Protease for proteins Nuclease for nucleic acids Trypsinogen (inactive) to active Trypsin which activates everything else. Exopeptidase – Terminal ends of proteins Endopeptidase – Interior of proteins Actions of luminal, brush border, and cytosolic proteases Partially digested products like oligopeptides Tripeptides Further broken down to a dipeptide Transported with a proton symporter into the cell as an intact tripeptide Dipeptide Individual Amino Acids Amino acids and their classification (neutral, basic, acidic; essential and non-essential) Amino Acids Neutral Allphatic Gly, Ala, Val, Leu, Ile Aromatic Tyr, Phe, Try Hydroxyl Ser, Thr Sulfur Cys, Met Imino Pro, Hydroxypro Basic Arg, Lys, His Acidic Glu, Gln, Asp, Asn Both enterocytes and specialized M cells can absorb whole, intact proteins (e.g. antigens) There are 2 types of transport mechanisms: Specialized cells called M cells Transports intact antigens through the mucosal gut wall Mucosal cell (enterocyte) Malabsorption of neutral (left) and cationic (basic) amino acids in heritable diseases Hartnup disease Phenylalinine transporter is missing Cystinuria Arginine transporter is missing Solved by producting a small dipeptide of the amino acid.