Diet 311 Coordinated Course in Physiology and Biochemistry PDF

BY DR. RICHARD DOE By the end of the course students should be able to: I. Demonstrate understanding of the mechanism of absorption of nutrients along the alimentary tract II. Understand the metabolic rate and factors regulating it III. Understand the neuro-endorcrine fact...

BY DR. RICHARD DOE By the end of the course students should be able to: I. Demonstrate understanding of the mechanism of absorption of nutrients along the alimentary tract II. Understand the metabolic rate and factors regulating it III. Understand the neuro-endorcrine factors that regulate energy balance in the individual  Digestion  Breakdown of ingested food  Absorption  Passage of nutrients into the blood  Metabolism  Production of cellular energy (ATP)  all the chemical and energy transformations that occur in the body  Ingestion  Mechanical processing  Digestion  Secretion  Absorption  Excretion DIGESTION degradation of structurally complex foodstuffs by digestive enzymes 3 categories of energy-rich foodstuffs: carbohydrates, proteins and lipids ABSORPTION absorbable units as a result of the digestive process a transported along with water, vitamins and electrolyt from the lumen of the GI tract into the blood and lym  DIGESTION Chemical degradation of nutrient macromolecules by digestive enzymes Luminal digestion: enzymes secreted into the lumen of GI tract from salivary glands, stomach and pancreas Membrane or contact digestion : hydrolytic enzymes synthesized by enterocytes and inserted into the brush border membranes. Integral part of the microvillar membrane in close vicinity of specific carrier proteins (= digestion-absorption coupling) Cytoplasmic digestion: digestive enzymes in the cytoplasm (peptidases)  Disassembles organic food into smaller fragments  Hydrolyzes carbohydrates, proteins, lipids and nucleic acids for absorption  Begins in the mouth  Salivary and pancreatic enzymes  Disaccharides and trisaccharides  Brush border enzymes  Monosaccharides  Absorption of monosaccharides occurs across the intestinal epithelia Diet contains digestible carbohydrates monosaccharides: glucose, fructose, sorbitol, (galactose in form of milk lactose = galactose+glucose) disaccharides: sucrose, lactose, maltose oligosaccharides/polysaccharides: starch (made of amylose and amylopectin), dextrins, glycogen non-digestible carbohydrates Dietary fibers, mainly cellulose (ß-1,4 linked glucose polymer; humans lack enzyme to hydrolyse ß-1,4 bonds). Fibers are extremely important for regular bowel movements. Digestive enzymes break down oligosaccharides and polysaccharides into the 3 absorbable monosaccharides glucose fructose galactose Digestive enzymes for carbohydrate digestion luminal digestive enzymes brushborder enzymes Luminal digestive enzymes for carbohydrate digestion: salivary and pancreatic amylase: cleaves the -1,4 glycosidic bond of amylose and amylopectin (starch and glycogen) to produce maltose, maltotriose and -limit dextrins. Note:  -amylase cannot hydrolyze  -1,6 and terminal  -1,4 glycosidic bonds. 87 Brush border enzymes digest disaccharides and oligosaccharides Enzyme Substrate Site of Products action sucrase sucrose -1,2 glycosidic glucose and fructose linkage lactase lactose ß-1,4 glycos. linkage glucose and galactose   isomaltase -limit dextrins -1,6 glycos. linkage glucose, maltose and (= -dextrinase) oligosaccharides   glucose maltase maltose -1,4 glycos. linkage glucoamylase maltooligosaccharides  glucose -1,4 glycos. linkage Digestion-absorption coupling G2 G3 88 Absorption mechanism of monosaccharides Digestion by brush border enzymes occurs in close vicinity to monosaccharide transporters. Glucose and galactose: SGLT1 absorption via a secondary active (uphill), Na-dependent transport Fructose: GLUT5 absorption by facilitated (carrier mediated), Na-independent mechanism K+ Brush border GI tract lumen Na + Galactose ATP Glucose SGLT1 Galactose Na + Glucose GLUT2 mucosa capillar Fructose 2 GLUT5 Fructose 90  Low pH destroys tertiary and quaternary structure  Enzymes used include pepsin, trypsin, chymotrypsin, and elastase  Liberated amino acids are absorbed Proteolytic digestive enzymes gastric secretion (G) pancreatic secretion (P) brush border enzymes (BB) cytoplasmic (C)  Endopeptidase: hydrolyzes internal peptide bonds: trypsin (P) chymotrypsin (P) elastase (P) pepsin (G) Exopeptidase: hydrolyzes external peptide bonds: carboxypeptidase A (P) carboxypeptidase B (P) aminopeptidase (P, BB, C) P = pancreas, BB = brush border, C = cytoplasm Protein digestion >> Gastric proteolysis: pepsin is activated by low pH from proenzyme pepsinogen and acts as endopeptidase. >> Small intestine: major site of protein digestion. Luminal protein digestion: Pancreatic proteases are secreted as inactive proenzymes. Chyme in the duodenum stimulates the release of enterokinase (= enteropeptidase) which converts trypsinogen into trypsin (active form). Trypsin itself converts the other proenzymes to active enzymes. Luminal protein digestions produces single amino acids and small peptides (dipeptides, tripeptides and tetrapeptides) Brush border peptidases are integral membrane proteins produce single amino acids and smaller peptides from tetrapeptides and larger peptides. Intracellular cytoplasmic peptidases break down dipeptides and tripeptides into single amino acids.  PROTEIN ABSORPTION: Products of protein digestion are absorbed as amino acids:7 amino acid transporters in brush border membrane (B&L, table 39-2): - 5 Na-dependent transporters (absorption occurs via secondary active process by carrier that are energetically coupled to the Na+ concentration gradient across the brush border membrane of intestinal epithelial cells) - 2 Na-independent transporters (facilitated transport). peptides: di- and tripeptides by peptide transporters. proteins: in the newborn of some animal species absorption of immunoglobulins provides an important form of passive immunity). Amino acid transport across the basolateral membrane 5 classes of amino acid transporter at the basolateral membrane (B&L, table 39-3) - 2 Na-dependent - 3 Na-independent Amino acids are transported in the portal blood protein digestion & absorption 95  Lipid digestion utilizes lingual and pancreatic lipases  Bile salts improve chemical digestion by emulsifying lipid drops  Lipid-bile salt complexes called micelles are formed  Micelles diffuse into intestinal epithelia which release lipids into the blood as chylomicrons Lipids in the GI tract: exogenous (diet: triglycerides (90%), phospholipids, sterols (e.g. cholesterol), sterol esters) endogenous (bile, desquamated intestinal epithelial cells) Digestion of lipids Most of the lipids are digested in the small intestine, but also in stomach. Enzymes for lipid digestion lingual lipase (from salivary secretion; break down of mainly medium-chain triglycerides as abundant in milk; optimal pH = 4 -- > lipid digestion in the stomach) gastric lipase (secreted by chief cells) pancreatic lipase = glycerol ester hydrolase (triglycerides) pancreatic phospholipase A2 (phospholipids) pancreatic cholesterol esterase (cholesterol ester). Mechanism of lipid absorption The intestinal villi are coated by an unstirred water layer which reduces the absorption of the poorly water soluble lipids.  Emulsification: In the small intestine lipids are emulsified by bile acids (i.e. formation of small droplets of lipids coated with bile acids). Bile salts (bile salts = conjugation of bile acids with taurine or glycine) are polar and water soluble, and function as detergents. Emulsion droplets allow access of the water-soluble lipolytic enzymes by increasing surface area.  Micelle formation and lipid absorption: - At a certain concentration (critical micellar concentration) bile salts aggregate into micelles that incorporate lipid digestion products. Lipids become water soluble by micellar solubilization. - Lipids diffuse across the unstirred water layer as micelles and are mostly absorbed passively (diffusion) by enterocytes (mainly in the jejunum). - Absorption is enhanced by Na+-dependent long-chain fatty acid transport protein (MVM-FABP=microvillous membrane fatty acid-binding protein) and cholesterol transport protein in the brush border membrane (secondary active and facilitated transport).  In the enterocytes lipids are bound by cytosolic lipid transport proteins and transported to the smooth endoplasmic reticulum. There triglycerides are reassembled from fatty acids and monoglycerides Triglycerides together with lecithin, cholesterol and cholesterol ester, are packaged into lipoproteins to form water- soluble chylomicrons (lipid aggregates). Transport of lipids to the lymphatic vessels by exocytosis. Additionally, mainly medium-chain and short-chain fatty acids directly reach the blood stream and are transported bound to serum albumin.  Absorption of bile acids. Bile acids are absorbed in the terminal ileum by Na+-dependent secondary active transport (mainly conjugated bile acids) and by diffusion (mainly unconjugated bile acids). Bile acids are recirculated to the liver via portal circulation and extracted from portal blood for reuse. Vitamins: organic substances needed in small quantities for normal metabolic function, growth and maintenance of the body. Fat-soluble vitamins: Vitamins A, D, E and K Water-soluble vitamins: Vitamins B1, B2, B6, B12, niacin, biotin and folic acid  Water-soluble vitamins (cont.): Absorption of Vitamin B12 Vitamin B12 (cobalamin) is bound to a cobalamin binding protein (intrinsic factor) secreted by the parietal cells of the stomach. The Vitamin B12-intrinsic factor complex is absorbed in the terminal ileum. Transport in the blood of Vitamin B12 by binding to the protein transcobalamin. Vitamin B12 is stored in the liver.  Water  Nearly all that is ingested is reabsorbed via osmosis  Ions  Absorbed via diffusion, cotransport, and active transport  Vitamins  Water soluble vitamins are absorbed by diffusion  Fat soluble vitamins are absorbed as part of micelles Vitamin B12 requires intrinsic factor Figure 24.27  When a person become dehydrated there is large amounts of aldosterone secreted by the adrenal glands (cortices)  Within 1-3 hrs this aldosterone causes activation of enzymes and transport mechanism for all aspects of Na⁺ absorption by the intestinal epithelium  There is also 2◦ reabsortion of Cl -, H2O and order substances  This will prevent loss of Na Cl in the feaces and little H2O loss Gastric mucosal barrier (1) unstirred, bicarbonate rich mucus layer maintains pH 7 at cell surface and protects gastric mucosa from gastric juice (pH 2) (2) tight junctions between gastric mucosal cells prevent penetration of HCl between cells (3) luminal membrane of gastric mucosal cells is impermeable for protons Protection against self-digestion 70 Figure 24.14 Upper esophageal sphincter Sphincters Lower esophageal sphincter 3  Movement of materials along the digestive tract is controlled by:  Neural mechanisms  Parasympathetic and local reflexes  Hormonal mechanisms  Enhance or inhibit smooth muscle contraction  Local mechanisms  Coordinate response to changes in pH or chemical stimuli Figure 24.5 Figure Figure Figure  Pancreatic duct penetrates duodenal wall  Endocrine functions  Insulin and glucagons  Exocrine functions  Majority of pancreatic secretions  Pancreatic juice secreted into small intestine  Carbohydrases  Lipases  Nucleases  Proteolytic enzymes Secretory functions of the pancreas: endocrine pancreatic secretion (islets of Langerhans): hormones (insulin, glucagon, somatostatin) essential for regulation of metabolism exocrine pancreatic secretion: aqueous component enzyme component Figure Digestive function production and secretion of digestive enzymes neutralization of acidic chyme (pancreatic enzymes pH optimum near neutral pH) Protective function neutralization of acidic chyme --> protection from acid damage of intestinal mucosa  Pancreatic enzymes Enzyme specific hydrolytic activity Enzyme activation Proteolytic enzymes are secreted in inactive zymogen form. Enteropeptidase (= enterokinase) secreted by duodenal mucosa activates trypsinogen (--> trypsin). Trypsin activates itself and the other proteolytic enzymes. Trypsin inhibitor: protein in pancreatic secretion that prevents premature activation of proteolytic enzymes in pancreatic ducts -amylase is secreted in active form Cellular mechanism of pancreatic secretion: carbonic anhydrase reaction produces H2CO3 Na/H exchange and H/K-ATPase eliminate H+ Cl-/HCO3- exchange secretes bicarbonate into duct lumen Carbonic electrogenic Cl channels - anhydrase recycle Cl- back into lumen Acid tide: net H+ release into the blood stream during pancreatic secretion.  Neural and hormonal mechanisms coordinate glands  GI activity stimulated by parasympathetic innervation  Inhibited by sympathetic innervation  Enterogastric, gastroenteric and gastroileal reflexes coordinate stomach and intestines Figure 24.22 Secretory functions of the pancreas: endocrine pancreatic secretion (islets of Langerhans): hormones (insulin, glucagon, somatostatin) essential for regulation of metabolism exocrine pancreatic secretion: aqueous component enzyme component 98 Digestive function production and secretion of digestive enzymes neutralization of acidic chyme (pancreatic enzymes pH optimum near neutral pH) Protective function neutralization of acidic chyme --> protection from acid damage of intestinal mucosa  Pancreatic enzymes Enzyme specific hydrolytic activity Enzyme activation Proteolytic enzymes are secreted in inactive zymogen form. Enteropeptidase (= enterokinase) secreted by duodenal mucosa activates trypsinogen (--> trypsin). Trypsin activates itself and the other proteolytic enzymes. Trypsin inhibitor: protein in pancreatic secretion that prevents premature activation of proteolytic enzymes in pancreatic ducts -amylase is secreted in active form Cellular mechanism of pancreatic secretion: carbonic anhydrase reaction produces H2CO3 Na/H exchange and H/K-ATPase eliminate H+ Cl-/HCO3- exchange secretes bicarbonate into duct lumen Carbonic electrogenic Cl channels - anhydrase recycle Cl- back into lumen Acid tide: net H+ release into the blood stream during pancreatic secretion. 72  Performs metabolic and hematological regulation and produces bile  Histological organization  Lobules containing single-cell thick plates of hepatocytes  Lobules unite to form common hepatic duct  Duct meets cystic duct to form common bile duct Figure Figure Figure Functions of the liver Energy metabolism and substrate interconversion Synthetic function Transport and storage function Protective and clearance function Bile secretion = digestive/absorptive function of the liver Components of bile bile salts (conjugates of bile acids) bile pigments (e.g. bilirubin) cholesterol phospholipids (lecithins) proteins electrolytes (similar to plasma, isotonic with plasma) 600-1200 ml/day Function of bile bile salts (conjugates of bile acids with taurine or glycine) important for absorption of lipids in small intestine. Bile acids emulsify lipids and form mixed micelles necessary for lipid absorption. bile acids are derived from cholesterol and therefore are responsible for excretion of cholesterol. excretion of bilirubin (product of hemoglobin degradation). bile acids are actively absorbed and recirculated through enterohepatic circulation. enterohepatic circulation of bile 73 Mechanism of uptake and secretion of bile acids by hepatocytes ATP 74 Intestinal secretion: 1500 ml/day. Composition: mucus electrolytes water