Digestive System and Metabolism spr 2k24 PDF

Digestive System Chapter 21  Average American Diet Consists of: Carbohydrates: polysacchrides (chains of sugar molecules) and disaccharides (sucrose, maltose, & lactose) Examples: Breads, sugars Proteins: chains of amino acids Examples: meats, soy Fats:...

Digestive System Chapter 21  Average American Diet Consists of: Carbohydrates: polysacchrides (chains of sugar molecules) and disaccharides (sucrose, maltose, & lactose) Examples: Breads, sugars Proteins: chains of amino acids Examples: meats, soy Fats: triglycerides (glycerol with 3 fatty acid chains attached) Cholesterol Long chain fatty acids Examples: grease, oils, butter  Average American Diet Most of these molecules have to be broken down into smaller molecules before they can be absorbed from the lumen of the digestive tract into the body and distributed for use by cells. The primary function of the digestive system is the breaking down (digestion) of these food molecules into smaller molecules so that they can be absorbed and used by the cells of the body.  Basic Physiologic Processes of the Digestive System The four basic physiologic processes of the digestive system are: digestion1, motility2 , absorption3, and secretion4. Secretion involves the movement of water, electrolytes, mucus, acid, and enzymes, 4 into the lumen or into Digestion involves the mechanical and the extracellular fluids 1 (ex. hormones) chemical breakdown of food 3 Absorption involves Motility involves the 2 the movement of movement of molecules from the materials within the lumen into the lumen due to action extracellular fluids of smooth muscle in (may be active or wall of digestive passive) tract.  Digestive System Anatomy Mouth → Oral cavity → Esophagus → Stomach → Small Intestine → Large Intestine → Rectum → Anus Mouth 3 Associated organs: Salivary glands Pancreas Liver Anus  The Stomach After the initial processing of food in the oral cavity the food bolus is swallowed into the esophagus. The esophagus passes through the diaphragm and attaches to the stomach. The stomach serves as a temporary holding pouch for ingested food. Its inner layer (called the mucosa) is folded into rugae to increase the surface are for secretion and allow the stomach wall the stretch as food enters from the esophagus. Food in the stomach is mixed with acid, mucus, and enzymes to create chyme. The pyloric valve (sphincter) regulates the passage of chyme into the small intestine. The Stomach Rugae The walls of the rugae are lined by secretory epithelial cells forming what are called gastric glands. The epithelial cells of the gastric glands secrete mucus, HCl acid, and inactive enzyme into the lumen of the stomach. Secretions of the stomach gastric glands include: Mucous and HCO3- from mucus cells (more later). HCl from the parietal cells. Also secrete a protein called Intrinsic Factor. Pepsinogen and gastric lipase from the Chief cells. Histamine from enterochromaffin cells, that stimulates the parietal cells to secrete HCl. Somatostatin from D cells, that inhibits the parietal cells from secreting HCl, the G cells from secreting gastrin, the enterochromaffin cells from histamine, and the Chief cells from secreting pepsinogen. A protein hormone, gastrin, from G cells, that stimulates both the parietal cells and enterochromaffin cells. Gastrin release is stimulated by: peptides and amino acids in the stomach lumen from digestion of proteins. distension of the stomach wall by food in the stomach lumen. (ex. local reflex in the digestive system mediated by the enteric nervous system.) Long reflexes mediated by CNS. (ex. sight of food stimulates increase in stomach secretions). Coordination of gastric secretions in the stomach: 1.The sight and presence of food in the oral cavity causes an increase in parasympathetic activity, which stimulates the G cells to secrete gastrin into the blood. (referred to as long reflexes mediated by the CNS). 2. As food moves into the stomach from the esophagus, short reflexes mediated by the enteric nervous system in the wall of the stomach are initiated and together with the presence of peptides and amino acids in the stomach lumen these serve to reinforce the parasympathetic stimulation of the G cells to secrete gastrin. 3.The gastrin acts to stimulate the parietal cells to secrete HCl and the enterochromaffin cells to secrete histamine, that also stimulates the parietal cells. 4. The HCl in the stomach lumen stimulates the chief cells to secrete pepsinogen and gastric lipase. 5. The HCl also stimulates D cells to secrete somatostatin, which acts as a negative feedback to modulate the secretion of acid and enzymes into the stomach lumen to help prevent over-secretion. The Small Intestine Similar to the stomach the mucosa of the small intestine is folded into what are called plicae. The plicae serve to increase the surface area of the small intestine for absorption of nutrients from the lumen. Digestive System Anatomy Revisted: Four Layers the Small Intestine Wall- The Mucosa Mucosa: Innermost layer of the GI tract. Composed of: Single layer of epithelial cells (see pink) that lines the lumen. Lamina propria (see yellow beneath pink) connective tissue, contains: Axons from neurons in the in the submucosal plexus, Blood/lymph capillaries, Aggregations of immune cells called Peyer’s patches. Muscularis mucosae (thin layer of smooth muscle).  Digestive System Functions: Secretion Normally 9 liters of fluid enter the lumen of GI tract everyday. 2 of the 9 liters enter through the mouth (i.e. are ingested as part of food and drink). The other 7 liters of fluid enter the lumen of the GI tract from body secreted along with, acid, electrolytes, enzymes and mucus. Half of this fluid comes from the accessory organs: the salivary glands, pancreas, and liver. The other half is drawn across the epithelial lining the GI tract by osmosis.  Digestive System Functions: Secretion of Ions and Water Na+, K+, Cl-, HCO3-, and H+ ions are secreted into the lumen of the GI tract as part of fluid secretions (ex. Saliva, pancreatic secretions, etc.). Most of these ions are subsequently reabsorbed as they move along the rest of the GI tract so they are not lost in the feces. These ions are transported via active transport, facilitated diffusion, and ion movement through open channels. Similar to the transport mechanisms to those in the kidneys. The presence of these ions in the GI lumen creates an osmotic gradient that draws water out of the interstitial fluid into the lumen of the GI tract through membrane channels or between the epithelial cells. The solution that results mixes with mucus in the lumen of the stomach and duodenum to thin it out so that it is able to mix with the digesting food to help lubricate it. Also, the enzymatic digestion of food requires water!  Digestive System Functions: Secretion of Stomach Acid 1-3 liters of HCl (hydrochloric acid) is secreted daily into the lumen of the stomach from the gastric glands. Creates a strongly acidic stomach luminal pH of 1. This high acidity serves three functions: It kills bacteria and other ingested micro-organisms (remember the mucus from the respiratory system is swallowed!). It converts the proenzyme pepsinogen into its active form pepsin. It denatures proteins that have been ingested causing them to unfold so that the peptide bonds between amino acids are accessible to enzymes during digestion in the small intestine. Digestive System Functions: Secretion of Stomach acid Summary of acid secretion by parietal cells: 1. Water molecules break down into H+ and OH- 2. H+ is actively pumped out 1 across the apical membrane of the parietal cell by a H+- K+ ATPase pump. 2 3. The parietal cells have 3 carbonic anhydrase (CA) that 4 catalyzes the reaction between OH- and CO2 to form HCO3-. 4. The HCO3- is pumped out 5 across the basal membrane in - exchange for Cl 5. Cl- flows out across the apical membrane through Cl- leak channels due to the presence of H+ in the lumen. Digestive System Functions: Secretion of Bile Bile is a nonenzymatic solution secreted from hepatocytes in the liver. Consists of: Bile salts that act as detergents to solubilize fats during digestion. (More later!) Bile pigments that are waste products of hemoglobin degradation Cholesterol Stored in gall bladder, which releases bile into the lumen of the duodenum during a meal (through the common bile duct). More Later! Digestive System Functions: Digestion and Absorption Digestion is the chemical and mechanical breakdown of food into absorbable units. Achieved by: Mastication (chewing) and mechanical mixing of ingested food in the stomach and small intestine (mechanical breakdown) Digestive enzymes (chemical breakdown). Absorption is the movement of nutrient molecules from the lumen into the interstitial fluids in the GI tract wall (may be active or passive). Small amount of absorption occurs in stomach (alcohol and aspirin). Most absorption occurs in the small intestine. Most epithelial cells that line the small intestine are specialized for absorption. Additional water, ions, and vitamins are absorbed in large intestine.  Digestive System Functions: Digestion and Absorption This figure shows an absorptive cell (enterocyte) from the small intestine apical The apical membrane of the enterocytes (absorptive cells) are basal Enterocyte aka folded into microvilli that serve to Absorptive cells further increase the surface area for absorption of nutrients in the small intestine. If you look at the surface of the GI lumen of the small intestine with a microscope the surface looks like it is covered with the bristles of a hair brush. This is why they refer to this surface as the “Brush border”.  Digestion of Dietary Food Molecules: Carbohydrates Begins in the mouth with oral amylase that breaks down starch into disaccharides (mostly maltose). Salivary amylase is optimally active at pH of 7. Since stomach acid destroys salivary amylase, and there is no secretion of carb digesting enzymes in the stomach, no carbohydrate digestion occurs in the stomach. Small intestine epithelial cells synthesize and express on their microvilli disaccharide-digesting enzymes: Sucrase Maltase Lactase These are referred to as “brush border enzymes” because they remain attached to the epithelial cells of the brush border. Pancreatic Amylase digests starch into maltose in small intestine.  Digestion of Dietary Food Molecules: Carbohydrates Ingested carbohydrates that enter the small intestine for digestion include: Starch (ex. breads, potatoes) Breakdown products of starch from salivary amylase digestion (maltose) Dietary disaccharides Sucrose (table sugar) Lactose (milk sugar) Maltose (grain sugar)  Digestion of Dietary Food Molecules: Carbohydrates In order to be absorbed dietary carbs must be digested into monosaccharides. Polysaccharides Oral and pancreatic Starts in mouth. None in stomach. Continues in small intestine by brush border enzymes. Digestive System Functions: Monosaccharide Absorption Figure 21-15 Na+-Glucose or Galactose symporter SGLT GLUT5 GLUT2 Na+/K+ GLUT = facilitated ATP diffusion pump GLUT2  Digestion of Dietary Food Molecules: Proteins Starts in the stomach via pepsin Pepsinogen is secreted in stomach by chief cells in the gastric glands as inactive proenzyme. Presence of H+ from stomach acid cleaves pepsinogen to its active form, pepsin, which begins protein digestion. Continues in small intestine via chymotrypsin and carboxypeptidase (pancreatic enzymes) after activation by the enzyme trypsin. Trypsin is secreted from the pancreas as the proenzyme trypsinogen, which is converted to trypsin by a brush border enzyme called enteropeptidase expressed by duodenal epithelial cells. The products of protein digestion are free amino acids, dipeptides, and tripeptides, which are small enough to be absorbed into the intestinal epithelial cells and in to blood.  Digestion of Dietary Food Molecules: Proteins The pancreas secretes most of the digestive enzymes that work in the small intestine. Pancreatic duct Brush border enzyme proenzymes Active enzymes Breaks down proteins Breaks down fats  Digestion of Dietary Food Molecules: Proteins Digestive enzymes of proteins cut peptide bonds. Divided into: Endopeptidases: cut peptide bonds in the interior of peptide chains. Examples: pepsin, trypsin, and chymotrypsin. Exopeptidases: cut peptide bonds on the ends of peptide chains. Examples: aminopeptidase, and carboxypeptidase. Digestive System Functions: Peptide Absorption Most individual amino acids are taken into the absorptive cells via a Na+ symporter, and then moved into the interstitial fluid via a Na+- amino acid antiporter. Di- and tripeptides are taken into the absorptive cells via H+ symporter, and then are either moved into the interstitial fluid via a H+ antiporter, or digested into individual amino acids. Larger peptides are carried across the absorptive cells by transcytosis.  Digestion of Dietary Food Molecules: Fats Dietary Fats: Triglycerides, cholesterol, phospholipids, long-chain fatty acids. Lipases are enzymes that break down triglycerides. Phospholipases break down phospholipids. Cholesterol is not digested before being absorbed. Most fat digestion occurs in the small intestine…  Digestion of Dietary Food Molecules: Fats Most fats in the diet are triglycerides. Triglycerides consist of a glycerol attached to 3 fatty acid side chains. Triglycerides are digested into monoglycerides and free fatty acids before being absorbed into the absorptive cells. glycerol Fatty acid chain  Digestion and Absorption: Fats Digestion of fats is complicated by the fact that they form fat droplets in the fluid in GI tract that cannot be penetrated by digestive enzymes. Bile salts are used to break the droplets up into smaller droplets. Large fat droplets Bile salts 1 from stomach from liver Bile salts from liver coat Increases 1 fat droplets. surface area for Bile Lacteal salts enzyme Emulsion Lipase can’t digestion. penetrate the bile salt coated Lumen of Micelles small intestine droplet Bile salts emulsions. After from liver fat droplets are coat fat emulsfied to droplets. Capillary Emulsions micelles, colipase Large fat is needed to droplets from Cells of displace some bile small stomach intestine salts so lipase can Pancreatic lipase penetrate the and colipase Break down fats droplets and into digest. monoglycerides Interstitial and fatty acids fluid stored in micelles. Lacteal Capillary Lumen of small intestine Cells of small intestine Interstitial fluid  Digestion and Absorption: Fats Large fat droplets Bile salts 1 Bile salts from liver coat from stomach from liver Bile salts 1 fat droplets. recycled Bile 2 Pancreatic lipase and Emulsion colipase break down Lacteal salts Fat emulsions into monoglycerides Lipase and fatty acids further breaking the 2 droplets down in small er and colipase droplets called micelles. Micelles Lumen Micelles of small intestine Bile salts from liver coat fat droplets. Capillary Emulsions Fats are lipophilic and so can cross cell Large fat droplets from Cells of small membranes stomach intestine Pancreatic lipase and colipase Monoglycerides and fatty Break down fats acids move out of micelles into and enter cells by diffusion. monoglycerides Assembled into triglycerides Interstitial on the smooth ER and fatty acids fluid stored in micelles. Lacteal Capillary Lumen of small intestine Cells of small intestine Interstitial fluid  Digestion and Absorption: Fats Large fat droplets Bile salts from Bile stomach salts 1 from liver 1 Bile salts from liver coat recycled fat droplets. Cholesterol is Bile transported 2 Pancreatic lipase and salts intoEmulsion cells. colipase break down Lacteal Fat emulsions into monoglycerides Bile salts and fatty acids further breaking the Lipase and colipase 2 Energy recycled droplets down in smaller droplets called micelles. Lumen Micelles of Micelles dependent small intestine transport of Monoglycerides and 3a 3a Bile salts cholesterol fatty acids move out of micelles and enter absorptive from liver cells by diffusion across the coat fat apical membrane. droplets. Capillary Emulsions Large fat Cells of droplets from small stomach intestine Pancreatic lipase and colipase Monoglycerides and fatty Break down fats acids move out of micelles into and enter cells by diffusion. monoglycerides Assembled into triglycerides Interstitial and fatty acids on the smooth ER fluid in micelles. stored Lacteal Capillary Lumen of small intestine Cells of small intestine Interstitial fluid  Digestion and Absorption: Fats Large fat droplets Bile salts 1 Bile salts from liver coat Bile saltsfrom stomach 1 from liver Triglycerides combine fat droplets. recycled Cholesterol is with cholesterol and proteins in the absorptive Bile transported cells to form Pancreatic 2 lipase and Lacteal Emulsion into cells. colipase break down salts chylomicrons. Fat emulsions into monoglycerides Bile salts and fatty acids further breaking the Lipase 2 recycleddroplets down in small er and colipase droplets called micelles. Cholesterol + triglycerides + protein Micelles Micelles Lumen of small intestine 3b Monoglycerides and 3a 3a Bile salts fatty acids move out of from liver micelles and enter absorptive cells by diffusion across the coat fat Chylomicron apical membrane. droplets. Capillary Emulsions Makes these 3b Cholesterol is lipids water- transported into cells Large fat Cells of Smooth by a membrane droplets from small ER soluble for transporter. stomach intestine release into the Pancreatic lipase interstitial fluid and colipase Monoglycerides and fatty Break down fats acids move out of micelles into and enter cells by diffusion. monoglycerides Assembled into triglycerides Interstitial and fatty acids on the smooth ER stored influid micelles. Lacteal Capillary Lumen of small intestine Cells of small intestine Interstitial fluid  Digestion and Absorption: Fats Large fat droplets Bile salts from Bile stomach salts 1 from liver 1 Bile salts from liver coat recycled Triglycerides combine fat droplets. with cholesterol and Transferred proteins in the absorptive Bile Cholesterol is transported cells to form 2 Pancreatic lipase and Lacteal to venous Emulsion colipase break down salts into cells. chylomicrons. Fat emulsions into monoglycerides blood Bile salts and fatty acids further breaking the Lipase 2 recycled droplets down in small er through and colipase droplets called micelles. Cholesterol + triglycerides + protein Micelles lymphatic Lumen Micelles of small intestine ducts 3b 3a 3a Monoglycerides and are Chylomicrons Bile salts fatty acids move from removed out ofthe from liver micelles interstitial and enterfluid absorptive by Chylomicron cells by The diffusion across the lymphatic coat fat Golgi apical membrane. system. droplets. Smooth apparatus Capillary Emulsions ER 3b Cholesterol is 4 Triglycerides + cholesterol + protein transported into cells Chylomicrons too big to cross Large fat Cells of Smooth by a membrane droplets from Chylomicron ER transporter. capillary wall and so cannot small stomach intestine Golgi enter the blood apparatus Pancreatic lipase Chylomicrons are packaged 4 Absorbed fats combine and colipase Monoglycerides and fatty with into secretory cholesterol vesicles by Break down fats acids move out of micelles and proteins in the into and 5 enter cells by diffusion. Golgi apparatus andto form intestinal cells monoglycerides Assembled into triglycerides chylomicrons. Interstitial and fatty acids on the smooth ER exocytosed into the fluid in micelles. stored Lacteal in villi interstitial fluid. Capillary 5 Chylomicrons are Lymph released into the IF and taken to into the lacteals of the Lumen of small intestine Cells Interstitial fluid venaof small intestine lymphatic system. cava  Regulation of Digestion in the Small Intestine Digestion in the small intestine is regulated by the nervous system and hormones. Chyme in the small intestines initiates local reflexes in the enteric nervous system to slow gastric motility and secretion. This serves to slow the movement of chyme from the stomach into the small intestine. Also, 4 hormones released from endocrine cells in the intestinal epithelium reinforce this: Secretin: Released into the blood when chyme enters duodenum Inhibits stomach acid production and slows gastric emptying Stimulates production of pancreatic HCO3- to neutralize acidic chyme moving into duodenum.  Regulation of Digestion in the Small Intestine Cholecystokinin (CCK) If a meal contains fats, CCK is secreted into blood. Acts to slow gastric motility and acid secretion. Because fat digestion is slow, CCK allows the stomach to deliver only small amounts of fat at a time to allow fat digestion time to occur. Stimulates gall bladder to release bile. Gastric inhibitory peptide (GIP) and Glucagon-like peptide-1 (GLP-1) If a meal contains carbs, GIP and GLP-1 are released into the blood to inhibit gastric secretion and motility, and stimulate insulin release into the blood by the pancreas.  Regulation of Digestion in the Small Intestine Bile release into duodenum: Occurs when gall bladder is stimulated to contract by CCK following fat ingestion. The secretion of bile into the small intestine promotes fat digestion. Bile salts are not physically altered by involvement in fat digestion. Reabsorbed back into the blood at the end of the small intestine. Liver removes them from the blood and reuses them to make more bile.  Large Intestine Functions Motility: Chyme enters the large intestine from the last part of the small intestine, called the ileum. The ileocecal valve controls movement of material from the small to large intestine, and prevents backward movement (i.e. from large intestine to small intestine. Chyme continues to be mixed in the large intestine by segmental contractions. “ Mass movement” segmental contraction waves push a bolus of material forward along the lumen of the large intestine 3-5 times per day. Distention of the rectal wall (terminal end of the large intestine) triggers defecation reflex that pushes feces out through the anus.  Large Intestine Functions Digestion: No digestive enzymes are secreted in the large intestine. Bacteria in the large intestine break down undigested complex carbohydrates and proteins through fermentation to produce lactate, short chain fatty acids, and butyric acid that are absorbed across the wall of the large intestine. Bacteria in the large intestine also produce absorbable vitamins, such as vitamin K. Absorption: By the time the chyme reaches the large intestine most of its original volume has already been reabsorbed. The large intestine absorbs most of the remaining water and ions in the chyme and concentrates the chyme into feces in preparation for defecation. Of the 9 liters of fluid that move along the GI tract in a day, normally only about 0.1 liter of water is lost through the feces.  Chapter 22 Metabolism Definition of metabolism: The sum of all metabolic (chemical) reactions that occur in the body. In order to maintain living tissue (i.e. maintain cell structure, run ion pumps that maintain concentration gradients, etc.), a constant energy expenditure is required. This energy is obtained primarily through chemical conversion of the energy in the bonds of nutrient molecules (glucose, fatty acids, amino acids and others) into the bonds of ATP through the metabolic processes of glycolysis and cellular respiration. This is why you have to eat food.  Metabolism and Energy Balance Once food has been digested and absorbed into the body, the body’s metabolic state determines what becomes of the nutrient molecules: Is the energy in the bonds of the nutrient molecules used to generate heat for maintaining a constant body temperature? Is the energy in the bonds of the nutrient molecules used in the synthesis of molecules for maintaining cell structure? Is the energy in the bonds of the nutrient molecules stored as fat by adipose cells?  Metabolic Pathways Metabolic pathways are chains of chemical reactions that occur in cells. Metabolic pathways: Extract energy from nutrient molecules (ex. glucose) Use energy for work (ex. protein synthesis) Convert some of the energy in the bonds of nutrient molecules into the bonds of storage molecules for later use (ex. cell respiration). These pathways can be divided into: Anabolic pathways: synthesize larger molecules from smaller ones (ex. protein synthesis). Catabolic pathways: break large molecules into smaller ones (ex. Glycogenolysis: the breaking down of glycogen to glucose).  Metabolic Pathways Overall body metabolism can be divided into two states: Fed State / Absorptive State: Occurs in the period of time following a meal when the products of digestion are being absorbed, used for energy, and/or stored. The energy needs of the cells during this metabolic state are being met by metabolism of absorbed nutrients. Anabolic metabolism predominates. The energy of nutrient molecules is being transferred into high energy compounds (ATP) or stored in the chemical bonds of other molecules. Fasted State / Post-absorptive State: Occurs in the period following the fed state when no more free nutrients are available for energy. The energy needs of the cells are being met by metabolism of nutrient molecules obtained from breakdown of larger molecules already in the cells. Catabolic metabolism predominates. The cells use stored energy by breaking down large molecules into smaller molecules. Converting the energy in the bonds of the large molecules into those of ATP (breaking chemical bonds releases energy).  Fate of Absorbed Nutrient Molecules The nutrient molecules absorbed across the digestive tract are used in one of three ways in the cells of the body: Energy use: Nutrient molecules can be metabolized immediately with the energy released from broken chemical bonds converted into the bonds of ATP, phosphocreatine, or other high energy compounds. This energy can then be used by the cell to do work. Synthesis: Nutrient molecules entering cells can be used to synthesize basic components for growth and cell maintenance. Storage: If the ingested amount nutrient molecules exceeds the energy and synthesis requirements of the body, the excess energy can be stored in the bonds of glycogen and/or fat, which can be used in times of fasting. The fate of the absorbed nutrient molecules depends on whether it’s a monosaccharide, amino acid, or fat, and the metabolic state of the body.  Fate of Nutrient Molecules during Fed State Metabolism Monosaccharides (glucose, galactose, fructose): Most (70%) of the absorbed monosaccharides will be taken up by cells and used immediately for energy through aerobic metabolism (glycolysis and cell respiration). Glycolysis ATP & pyruvate cell respiration CO2 + H2O & ATP Some of the remaining monosaccharides will be taken up by the liver and skeletal muscles and converted to glycogen through a process called glycogenesis, and stored in the liver and skeletal muscles. Some will be taken up by the liver and used in the synthesis of lipoproteins. If there are excess monosaccharides, they are taken up by adipose cells and converted to triglycerides through a process called lipogenesis, and stored in adipose cells.  Fate of Nutrient Molecules during Fed State Metabolism Amino acids: Most absorbed amino acids will be taken up by cells and used for protein synthesis (ex. lipoproteins, plasma proteins, cytoskeleton, enzymes, hormones) If glucose intake is low, some of the absorbed amino acids will be taken up by the liver and converted to glucose via a process called gluconeogenesis Gluconeogensis :The formation of glucose from noncarbohydrate precursors, such as amino acids and the glycerol portion of triglycerides. Any excess amino acids that aren’t used in the above ways will be taken up by adipose cells and converted to triglycerides and stored in adipose the adipose cells.  Fate of Nutrient Molecules during Fed State Metabolism Fatty acids, monoglycerides and cholesterol: The free fatty acids, monoglycerides, and cholestrol that are absorbed from the digestive tract are assembled into chylomicrons that are subsequently released into the interstitial fluid in the wall of the digestive tract and taken up into the lacteals (lymph capillaries) in the villi of the small intestine. The chylomicrons are transported with the lymph through the lymphatic system and pass through the lymphatic ducts into the venous circulation. The fate of these molecules is summarized on the next slide. 1. Chylomicrons enter the blood and are broken down in the blood into free fatty acids (FFA) and glycerol by lipoprotein lipase (lpl, bound to capillary endothelial cells in muscle and adipose tissue). What is left after this are chylomicron remnants (CM, mostly cholesterol) and high density lipoprotein complexes (HDL-C). 2. The FFA and glycerol are taken up by adipose cells and most other cells of the body. In the adipose cells they are reassembled into triglycerides and stored. In most other cells 1 they are used in cell respiration for producing ATP. 2 3. The CM remnants and HDL-C are taken up by the liver where they are metabolized. Some of the cholesterol is excreted in the bile, but is 3 4 repackaged with FFA and lipoproteins into low density lipoprotein complexes (LDL-C) and exocytosed into the blood. 4. The LDL-C are subsequently taken up by most cells of the body and metabolized and the cholesterol used for synthesis of other molecules.  Fate of Biomolecules during Fasted State Metabolism Plasma glucose levels begin to fall when all nutrients have been distributed to various cells. When this occurs cells switch to fasted state metabolism (more on how this switch happens in a minute!). In fasted state metabolism, biomolecules (proteins, glycogen, fats) are metabolized to meet the energy needs of the cells. GOAL of the fasted state metabolism: Maintain plasma glucose concentrations within an acceptable range so that the brain and neurons have adequate fuel. Neurons primarily use metabolism of glucose for producing the energy they need.  Fate of Biomolecules in Fasted State This figure summarizes what happens in the fasted state metabolism. FASTED-STATE METABOLISM Liver becomes the primary source of glucose for the body. Liver glycogen stores Glycogenolysis Energy production Glucose glucose released into the blood for the body. Glucose Energy production  Fasted-State Metabolism FASTED-STATE METABOLISM Liver becomes the primary source of glucose for the body. Liver glycogen stores Glycogenolysis Via Citric Acid Cycle Energy production Glucose Energy production Glycogen Gluconeogenesis Pyruvate or Lactate Glucose Muscle tissue can’t convert its glycogen stores into glucose. Instead converts it to pyruvate or lactate, which are released into the blood and taken up by the Energy production liver and converted to glucose by gluconeogenesis. Some of the pyruvate is also used by the muscle tissue for energy production reducing its need for glucose.  Fasted-State Metabolism FASTED-STATE METABOLISM Liver becomes the primary source of glucose for the body. Liver glycogen stores Glycogenolysis Via Citric Acid Cycle Energy production Glucose Energy production Glycogen Proteins Gluconeogenesis Pyruvate or Lactate Amino Glucose acids Additional glucose can also come from the breakdown of Energy production muscle proteins into amino acids. Some of these amino acids are processed for energy and others are converted to pyruvate and released into the blood for conversion into glucose.  Fasted-State Metabolism In adipose cells stored triglycerides are FASTED-STATE METABOLISM broken down into free fatty acids and Liver becomes the primary source of glycerol that are released into the Triglyceride stores glucose for the body. blood and taken up by the liver Liver Free fatty glycogen Free fatty acids Glycerol stores acids Glycogenolysis Gluconeogenesis Energy production Glucose Energy production Glycogen Proteins Gluconeogenesis Pyruvate or Lactate Amino Glucose acids Energy production  Fasted-State Metabolism The liver converts FASTED-STATE METABOLISM the glycerol to glucose via gluconeogenesis, Triglyceride stores Liver becomes the primary source of and the free fatty acids glucose for the body. into ketones via Liver b- oxidation. Free fatty glycogen The resulting glucose Free fatty Glycerol acids stores and ketones are released acids into the blood. Glycogenolysis b-oxidation Gluconeogenesis Energy Ketone production Glucose bodies Energy production Glycogen Proteins Gluconeogenesis Pyruvate or Lactate Ketone Amino Glucose acids bodies Energy production Neural tissue can use only glucose or ketones for energy.  Homeostatic Control of Metabolism Endocrine system regulates minute to minute metabolic state via the protein hormones insulin and glucagon Insulin and Glucagon are synthesized and secreted by cells in the “Islets of Langerhans” (islands of endocrine cells) in the pancreas. - b Cells produce insulin - a Cells produce glucagon Secretion of these hormones is primarily regulated by blood glucose levels, and to some degree blood amino acid levels.  Homeostatic Control of Metabolism The Insulin: Glucagon ratio in the blood regulates metabolic state of most cells. In fed state, the rise in blood glucose levels stimulates secretion of insulin and inhibits the release of glucagon. Insulin secretion is also stimulated by GI tract hormones GIP and GLP-1 following a carbohydrate meal, and increased parasympathetic activity (ACh onto muscarinic receptors expressed on the b cells). So, insulin dominates in the fed state (insulin levels are high and glucagon levels are low). In fasted state, blood glucose levels fall, removing stimulation of insulin secretion and inhibition of glucagon secretion. Glucagon dominates in the fasted state (glucagon levels are high and insulin levels are low).  Homeostatic Control of Metabolism: Insulin Targets of insulin: liver, adipose tissue, and skeletal muscle tissues. Overall effect of insulin on target cells: increased uptake and use of glucose following a meal. Shifts cell metabolism into the absorptive (Fed) state The effects of Insulin lower blood plasma glucose levels in the four following ways: 1. Insulin increases glucose transport into insulin-sensitive cells: – Adipose tissues and resting skeletal muscle tissue require insulin for glucose uptake. – Insulin promotes the insertion and activation of GLUT4 transporters into the target cell membrane which allows glucose to be taken into the cell (by facilitated diffusion). Without insulin these tissues withdraw the GLUT4 transporters from their cell membrane and cannot take up glucose. Note: exercising skeletal muscle fibers don’t need insulin to insert the GLUT4 transporters into their cell membrane.  Homeostatic Control of Metabolism: Insulin 2. Insulin enhances cellular utilization of glucose: It activates the enzymes in pathways for glucose utilization (glycolysis) and for glycogen synthesis (glycogenesis). It simultaneously inhibits enzymes for glycogen breakdown (glycogenolysis), glucose synthesis (gluconeogenesis), and fat breakdown (lipolysis) to ensure cellular utilization of glucose that has been taken up. 3. Insulin enhances utilization of amino acids: It activates the enzymes involved in protein synthesis and inhibits the enzymes that promote protein breakdown. Amino acids from protein meals are used for protein synthesis in the liver and muscle tissue.  Homeostatic Control of Metabolism: Insulin 4. Insulin promotes fat synthesis in adipose cells: It inhibits the enzymes involved in pathways that break down triglycerides and stimulates the enzymes involved in the conversion of excess glucose or amino acids into triglycerides (lipogenesis). Excess triglycerides are stored as lipid droplets in adipose cells. Homeostatic Control of Metabolism: Insulin  Homeostatic Control of Metabolism: Glucagon When blood glucose levels decline (fall