Digestion, Absorption, and Transport

• Three processes are involved in using food in the body: digestion, absorption, and nutrient utilization.
• Major components of diets are starches, sugars, fats, and proteins.
• Hydrolysis of macromolecules facilitates absorption and metabolism.
• Starches and sugars are absorbed as monosaccharides
• Fats are absorbed as free fatty acids and glycerol
• Proteins are absorbed in their constituent amino acids and peptides.

Digestion

• It is the process of breaking down food into absorbable units.

Absorption

• It is the passage of nutrients from the gastrointestinal (GI) tract into the blood or lymph.

Transport

• It carries nutrients into the circulatory system and delivers them to cells.
• Sequence of digestion events: ingestion -> digestion -> absorption -> transport -> metabolism -> excretion.
• Digestion and absorption occur in the gastrointestinal tract.
• Gastrointestinal tract is 7-10 meters long from mouth to anus.
• The GI tract along with liver makes up about 3% of adult body weight
• Zone 1: Mouth and pharynx lead to the esophagus
• The esophagus is a pipe entering the stomach via a sphincter.
• The exiting of food from the stomach is governed by the pyloric sphincter, allowing food to pass into the small intestine (duodenum, jejunum, and ileum).
• Small intestine length is 2.8-8.5 m
• Men generally have longer small intestines than women.
• Chewing reduces particle size and increases the surface area for digestion.
• The stomach is a muscular sac that physically reduces food particle size. It also forms a barrier against bacteria entering the GI tract and releases enzymes to break down lipids and proteins.
• Thin emulsion of food entering the small bowel is neutralized by duodenal bicarbonate secretion and further digested by enzymes secreted by the pancreas.
• The process is aided by detergent salts secreted by the gallbladder.
• During passage in the jejunum, large amounts of water(9L) are secreted and reabsorbed with the product of luminal and brush-border digestion.
• Only 60-120 ml of fluid pass the ileocecal valve per hour, carrying undigested materials into the cecum to be metabolized via efficient reabsorption.
• Colonic fermentation generates short-chain fatty acids (SCFA) that stimulate salt and water absorption to produce stool.

Absorption Surface Amplifiers

• Folds or ridges (rugae) increase the absorptive area in the intestinal wall.
• Villi are finger-like projections, 0.5–1.0 mm long, covered with mucosal absorptive cells.
• Enterocytes increase the absorptive capacity of mammals with higher metabolic rates.
• Enterocytes have finger-like projections on luminal surface called microvilli, defining the brush-border membrane.
• These features increase the surface area of the human intestine to 200 m².
• The mouth chews and mixes food with saliva
• The esophagus passes food from the mouth to the stomach.
• The stomach adds acid and enzymes. The stomach also Churns and mixes to create a liquid mass.
• The liver manufactures bile salts to breakdown fat.
• The small intestine secretes enzymes that digest all energy-yielding nutrients into the bloodstream.

Digestive Secretions

• Salivary glands in the mouth produce saliva which eases in swallowing, and contains salivary enzyme to break down some carbohydrate.
• Gastric glands in the stomach produce gastric juices which mixes with bolus, contains hydrochloric acid to uncoil proteins, and contains enzymes to break down proteins, while mucus protects the stomach cells.
• Pancreas produces pancreatic juices which neutralizes the acidic gastric juices, and pancreatic enzymes break down carbohydrates, fats, and proteins.
• The liver produces bile that is stored until needed in the Gallbladder
• The gallbladder produces bile to emulsifies fat so that enzymes can have access to break it down.
• Intestinal glands in the small intestine produce intestinal juices to break down carbohydrate, fat, and protein fragments; and mucus protects the intestinal wall.
• Digestion breaks down foods into nutrients, involving the mouth, stomach, and small intestine.
• Absorption uptakes nutrients into small intestine cells for transport.
• Transport spreads nutrients through the circulatory system.
• A bolus is a lump of food swallowed at one time.

Small Intestine

• The majority of absorption takes place in the small intestine.
• It is about ten feet long
• It has a Large surface area

Absorption Techniques

• Simple diffusion
• Facilitated diffusion
• Active transport
• Nutrients are absorbed actively when they move against a concentration gradient and require energy. Nutrients,glucose and amino acids, must be absorbed actively.

Transport

• Bloodstream carries water-soluble nutrients and smaller products of fat digestion to the liver.
• Lymphatic system carries larger fats and fat soluble vitamins and also bypasses the liver at first.
• Carbohydrates are broken down to provide glucose for energy.
• Digestion of carbohydrates mainly occurs via enzymes lining the small intestine walls.
• Once absorbed, galactose and fructose are metabolized further by the liver to produce glucose and minimal amounts of other metabolites.

Digestion

• Starch hydrolyzing via saliva in the mouth is often small, as most food does not stay in the mouth long.
• When a food bolus reaches the stomach, salivary enzymes are denatured.
• Digestion mainly occurs in the small intestine with pancreatic amylase hydrolyzing starch to dextrin and maltose.
• Glucosidases enzymes on the brush border of the small intestine break down dextrin.
• Maltase, lactase and sucrase converts disaccharides into its two monosaccharides.
• At low concentrations, glucose is transported through the mucosal lining into the epithelial cells of the intestine via a sodium dependent transporter via active transport.
• At higher concentrations, a second facilitative transporter is involved.
• Glucose is moved from epithelial cells into surrounding capillaries via facilitated diffusion.
• Monosaccharide units (glucose, galactose, fructose) are transported through the small intestine wall into the portal vein, which takes them to the liver.
• Glucose and fructose are absorbed relatively quickly, based on concurrent nutrients eaten.
• Sugars absorb slower when eating meals with protein and fat
• Galactose is transported the same way as glucose, utilizing the same transporters.
• Because galactose isn't found as a monosaccharide in nature. Absorbed galactose mainly comes from lactose breakdown.
• Fructose moves entirely via facilitated diffusion.
• It uses a different transporter to glucose when entering the enterocytes.
• Fructose and glucose use the same transporter to exit the enterocytes into the capillaries.
• Individual monosaccharides are small molecules transported through the small intestine epithelium via membrane porters.
• Specialized porters are used for different monosaccharides, with both active and passive transport employed.
• Glucose and Galactose are transported by secondary active transport via Na+-Glucose or Na+-Galactose symporters.
• Energy for resorption is supported by an Na/K ATPase on the basolateral membrane of small intestine enterocytes.
• It reduces Na+ cytosolic concentration inside the cells, providing luminal resorption of sodium along with monosaccharides.
• Fructose is transported past the luminal membrane via passive diffusion down its electrochemical gradient. Therefore, fructose transport is much less efficient than that of glucose and galactose.
• Extra glucose is first stored as glycogen in the liver or muscles.

Glycogen storage

• The liver stores about 100 g of glycogen. It is used to maintain basal blood glucose levels between meals
• The muscles store 400-500 g, often for use during movement.
• Once reserves are filled, excess glucose is converted to fat for longer term storage.
• A major exception is dietary fibre; a soluble or insoluble polysaccharide.
• Most fat in the human diet is triacylglycerol (TAG), or three fatty acids linked to glycerol.
• Inside the digestive tract, TAG is hydrolyzed by pancreatic lipase to release free fatty acids and monoglycerides.
• Lipids are hydrophobic and poorly soluble in the digestive tract's aqueous environment.
• The digestive enzyme, pancreatic lipase, is water soluble, and it works on the surface of fat globules.
• Digestion is greatly aided by emulsification, which breaks fat globules into much smaller emulsion droplets.
• Bile salts and phospholipids are amphipathic molecules in bile.
• The small intestine’s motility breaks fat globules into droplets coated with bile salts and phospholipids that prevent droplet re-association.
• Emulsification greatly increases water-soluble pancreatic lipase’s surface area available to digest TAG.
• Colipase is an amphipathic protein that binds and anchors pancreatic lipase at the emulsion droplet surface.
• After digestion, monoglycerides and fatty acids associate with bile salts and phospholipids to make micelles that are 200x smaller v emulsion droplets.
• Micelles are necessary to transport insoluble monoglycerides and fatty acids to the enterocyte surface for absorption.
• Micelle formation is important for lipid absorption because emulsification and hydrolysis can occur on the surface of enterocytes.
• Micelles are constantly breaking down and reforming - feeding a small pool of monoglycerides and fatty acids that are in solution.
• Only freely dissolved monoglycerides and fatty acids are absorbed, not the micelles themselves.
• Given their nonpolar nature, monoglycerides and fatty acids can diffuse across the enterocyte plasma membrane. Some absorption needs specific transport proteins.
• The major products of lipid digestion, which are fatty acids and 2-monoglycerides, enter the enterocyte by simple membrane diffusion.
• A considerable fraction of fatty acids enter the enterocyte via a specific fatty acid transporter protein in the membrane.
• Once inside the enterocyte, monoglycerides and fatty acids are re-synthesized into TAG.
• TAG is packaged with cholesterol and fat-soluble vitamins into chylomicrons.
• Chylomicrons, lipoproteins, are specifically designed for lipid transport in the circulation.
• Chylomicrons enter circulation via lacteals, lymphatic capillaries poking up into the center of each villus.
• Chylomicrons deliver absorbed TAG to the cell. TAG in chylomicrons and other lipoproteins is hydrolyzed by lipoprotein lipase, an enzyme in capillary endothelial cells.
• Monoglycerides and fatty acids released after lipoprotein TAG digestion then diffuse into cells.
• High LDL cholesterol levels in the circulation increase the risk of developing atherosclerosis.
• Some cholesterol in the small intestine is dietary cholesterol and some from bile. Only half of the total cholesterol passing through the small intestine is typically absorbed; the rest is eliminated in feces. Thus, cholesterol in bile is a substance that is.
• Fat soluble vitamins travel in micelles and also absorbed by simple diffusion.
• Water soluble vitamins are absorbed by diffusion
• Vitamin B12 combines with intrinsic factor before transport into cells because it is receptor mediated endocytosis
• The body dumps 9L of fluid into the GI tract a day
• The small intestine reabsorbs 8L
• The large intestine reabsorbs 90% of the last litre.
• Absorption happens by osmosis by way of cell walls, Into vascular capillaries inside villi
• Proteins cannot be absorbed whole, therefore must be digested into Amino acids (Aas) or di- and tri-peptides prior to absorption.
• Digestion begins in the stomach and is accomplished by both gastric and pancreatic proteases, with pancreatic protease performing 70% of digestion.
• Given proteins' diverse structures, they require a broader spectrum of peptidases and transporters than carbohydrates.
• The gastric phase begins with secretion of pepsinogen from chief cells and HCl from parietal cells.
• HCl denatures proteins and converts inactive pepsinogen to active pepsin.
• Pepsin cleaves proteins at large aliphatic or aromatic side groups, completing 10-20% of protein digestion.
• As chyme enters the intestines, pepsin is inactivated (at pH > 4.5), protecting the intestines from autodigestion.

Gastric HCl

• It is responsible for low pH <2 of gastric juice.
• It kills microorganisms, denatures dietary proteins, and prepares them for hydrolysis by proteases.
• Gastric juices contain stable proteases of the pepsin family, producing large peptide fragments and free amino acids.
• After the amino acids and small proteins enter the duodenum, it triggers the release of cholecystokinin-pancreozymin (CCK-PZ) into the bloodstream.
• This release initiates the secretion of protease zymogens from the pancreas and release of enteropeptidase in the gut.
• Enteropeptidase converts pancreatic trypsinogen to trypsin.
• Intestinal phase is responsible for the bulk of proteolysis due to pancreatic proteases.
• 70% of proteins are converted to oligopeptides in the intestines.
• The two main forms of pancreatic enzymes are endopeptidases and exopeptidases.
• Endopeptidases cleave internal bonds while exopeptidases cleave AA at the C-terminus.

Enzymes

• Endopeptidases include trypsin, chymotrypsin, and elastase.
• Exopeptidases include carboxypeptidase A which acts on neutral AA, and carboxypeptidase B, which acts on basic AA.
• Pancreatic juice contains rich proenzymes of endopeptidase and carboxypeptidases.
• Enteropeptidase converts pancreatic trypsinogen to trypsin, which activates trypsinogen and other proenzymes, releasing chymotrypsin, elastase, and the carboxypeptidases A and B.
• Brush border contains additional protein digestion, increasing the amount of protein suited for intracellular transport.
• Brush border peptidases are integral membrane proteins that produce single amino acids and smaller peptides (di and tri-peptides) from larger peptides.
• Cytoplasmic peptidases break down dipeptides and tripeptides into single amino acids.
• The bloodstream takes in greater than 99% of protein in single amino acids.
• Pancreatic juice lacks appreciable aminopeptidase activity, So final digestion of di- and small peptides depends on brush border enzymes
• Intestinal epithelial cells cells have rich endopeptidases and aminopeptidases.
• End products of cell surface digestion is free amino acids and di- and tripeptides.
• Most protein absorption is in the duodenum and jejunum with transport of oligopeptides (3 to 4 AA and shorter) and AA.
• Oligopeptides have rapid absorption than free amino acids.
• Several different transporters perform different mechanisms like; active transporter and PEPT1.
• PEPT1 is coupled to sodium-hydrogen exchanger (NHЕ3). And it accommodates proteins of various sizes and charges.
• Free AA are transported by several different mechanisms;
• facilitated diffusion,
• Na+-independent carriers
• Na+-dependent carriers
• proton co-transport.
• If a large amount of one particular amino acid is consumed, the absorption of others can be inhibited if the acids share the same transport system.
• The enterocyte's basolateral membrane has additional transporters exporting amino acids from the cell into the blood by both diffusion and by both NA+ dependent and independent carriers
• Lipoprotein lipase hydrolyzes triacylglycerol (TAG) that is found in Chylomicrons
• The lymphatic capillaries that chylomicrons enter on their way to the circulation are called lacteals.
• Chylomicrons does not contain bile salts.
• When trypsin, chymotrypsin, and proelastase are active in the intestines thenThe intestinal phase is responsible for the bulk of protein digestion