L4-Biochemical Aspects of Protein & Carbohydrate Digestion 2 PDF

L4: Biochemical aspects of digestion of proteins and carbohydrates GNT Block Color Index: • • • • • • Main text Female slides Male slides Important Doctor’s notes Extra notes Editing file: Objectives: Understand the overall process of dietary proteins’ and carbohydrates’ digestion, the organs...

L4: Biochemical aspects of digestion of proteins and carbohydrates GNT Block Color Index: • • • • • • Main text Female slides Male slides Important Doctor’s notes Extra notes Editing file: Objectives: Understand the overall process of dietary proteins’ and carbohydrates’ digestion, the organs involved, the enzymes required, and the end products. Implement the basic science knowledge of the process of proteins & carbohydrates digestion to understand the clinical manifestations of diseases that involve defective proteins’ or carbohydrates’ digestion &/or absorption. Lecture presented by : Dr. Sumbul Fatma Ninja Nerd Dr. Ahmed Mujamammi Ninja Nerd Biochemical Aspects of Digestion of Dietary Proteins Protein digestion : Dietary proteins constitute 70-100 g/day Proteins are generally too large to be absorbed by the intestine They must, therefore,be hydrolyzed to their constituent amino acids, which can be absorbed. The source of proteolytic enzymes Responsible for Degrading Dietary Proteins ● ● ● Stomach Pancreas small intestine Digestion of protein in gastric secretion: The gastric juice contain 2 component important for protein digestion: Digesting agent Hydrochloric acid Pepsin Description Important 1. kills some bacteria 2. Denatures proteins— denatured proteins are more susceptible to hydrolysis by proteases. • • • • • Acid-stable Endopeptidase Secreted as inactive zymogen (pepsinogen) Pepsinogen is activated by: 1. hydrochloric acid 2. pepsin, i.e. autocatalysis Protein digestion by stomach —Polypeptides + few free amino acids Digestion of proteins in small intestine : 1- digestion by pancreatic enzymes. (requires enteropeptidase) 2-digestion by intestinal aminopeptidase. The digestion in small intestine is hormonally controlled. Two small peptide hormones are released from cells of the upper part of small intestine: 1. Cholecystokinin (CCK) 2. Secretin Hormonal control of digestion in small intestine: Cholecystokinin (CCK) Secretin -Secretion of pancreatic enzymes. -Bile secretion. -Slow release of gastric contents Release of watery solution rich in bicarbonate by pancreas. The gut hormones : The gut hormone Stimulus for secretion Effects 1. Stimulates the release of pancreatic digestive enzymes. Cholecystokinin (CCK) The presence of partially digested proteins (& lipids) in the upper small intestine 2. Stimulates the contraction of the gallbladder & release of bile. 3. Decreases gastric motility → slower release of gastric contents into the small intestine Secretin Low pH of the chyme entering the intestine Stimulates the pancreas to release a watery solution rich in bicarbonate to neutralize the pH of the intestinal contents (to reach the optimum pH for digestive activity by pancreatic enzymes) Pancreatic enzymes for digestion of proteins -The pancreatic secretion contains a group of pancreatic proteases. - Each of these enzymes has different specificity for the cleavage sites. -These proteases are synthesized and secreted as inactive zymogens. Activation of pancreatic enzymes Enteropeptidase converts trypsinogen to trypsin. Enteropeptidase is an enzyme synthesized by, and present on the luminal surface of intestinal mucosal cells of the brush border membrane. Trypsin then activates all the other pancreatic zymogens (including itself) Nothing is important in pic Important Zymogen Active enzyme Trypsinogen Trypsin Chymotrypsinogen Chymotrypsin Proelastase Elastase Procarboxypeptidases Carboxypeptidases Activating enzyme 1- Enteropeptidase 2- Trypsin (autocatalysis) Endopeptidase Break peptide bonds within the molecule. Trypsin Trypsin Exopeptidases Break peptide bonds from end-pieces of terminal amino acids Trypsin Digestion of proteins in small intestine Digestion by intestinal aminopeptidase Oligopeptides that result from the action of pancreatic proteases are cleaved into free amino acids and smaller peptides (di- & tripeptides) by intestinal aminopeptidase (an exopeptidase on the luminal surface of the intestine) Absorption of digested proteins Know name of enzyme Genetic Errors in Amino Acids Transport ( Cystinuria) Example of Organs affected inherited disorder in the transport of certain amino acids are the small intestine and the kidney 01 02 03 04 Management Oral hydration (drinking lots of water) is an important part of treatment (to prevent kidney stones formation) 05 06 COLA or COAL About the disease Cystinuria is one of the most common genetic error of amino acid transport Affects transport of Cystine and dibasic amino acids Cysteine: is a sulfur-containing amino acid. Cystine: is formed from two cysteine molecules joined together Clinically Cystine and dibasic amino acids appear in the urine, kidney stones formation mnemonic for dibasic -> Cystine, Ornithine, Lysine, Arginine Female Dr. its important to know all affected a.a a.a Abnormalities of protein digestion Pancreatic insufficiency, e.g., chronic pancreatitis, cystic fibrosis, surgical removal of the pancreas Incomplete digestion & absorption of lipids & proteins Abnormal appearance of lipids (steatorrhea) & undigested proteins in the feces Definition: It is a disease of malabsorption resulting from immune mediated damage to the villi of the small intestine in response to ingestion of gluten. Celiac Disease (Celiac sprue) Celiac disease is a hereditary disorder caused by sensitivity to the gliadin fraction of gluten, a protein found in wheat; similar proteins are present in rye and barley. In a genetically susceptible person, gluten-sensitive T cells are activated when gluten-derived peptide epitopes are presented. The inflammatory response causes characteristic mucosal villous atrophy in the small bowel. Gluten is a protein found in wheat, rye, and barley. The antibodies are against gliadin, a protein made of metabolism of gluten Biochemical aspects of digestion of dietary carbohydrate Carbohydrates Digestion: Rapid digestion because it starts in the mouth (physical chewing and alpha amylase enzyme) No carbs digestion in the stomach (due to high acidity) Carbohydrates digestion is rapid: Generally completed by the time the gastric contents reach the junction of the duodenum & jejunum. After neutralization of pH by secretin, the chyme now is in the intestines with more neutral pH and more enzymes are ready to start to work, this happens in the duodenum and upper jejunum Sites for digestion of dietary carbohydrates: ● The mouth ● The intestinal lumen It starts here Dietary Carbohydrates Mainly: Monosaccharide Disaccharides Little amounts ● Sucrose ● Lactose ● Maltose Oligosaccharides Polysaccharides • Glycogen from animal origin Contain α(1-4) & α (1-6) bonds • Starch from plant origin Dietary food contains little amounts of monosaccharides because it's expensive in the • Cellulose from plant origin β (1-4) bond food industry The structure is Extra Enzymes for Digestion of Dietary Carbohydrates Important Enzymes Cellulose is not absorbed by the body because there is no enzyme that cleaves its bond β(1-4) α-amylase -location: Both salivary & pancreatic. -Substrate: Polysaccharides Disaccharidases -location: Intestinal -Substrate: Disaccharides Isomaltase & α(1,6) glucosidase -location: Intestinal -Substrate: Branch points of oligo- and di-saccharides Effects of α-amylase on Glycogen Hydrolysis of: α(1,4) glycosidic bonds Productes: -Mixture of short oligosaccharides ( both branched & unbranched ) -Disaccharides: Maltose and isomaltose No dietary carbohydrate digestion occurs in the stomach (the high acidity of the stomach inactivates the salivary α–amylase) Pancreatic α–amylase continues the process of starch & glycogen digestion in the small intestine. (Secreted by pancreas and works in small intestine) Serum level of α-amylases very important for OSPE Normal level in serum: 25 -125 U/L The clinical significance of rising circulating levels of α-amylase activity: Diagnosis of acute pancreatitis: (damage of pancreatic cells —> release & activation of the intracellular enzymes into the blood) Its level starts to rise within few hours Reaches a peak within 1272 hours. Then returns to normal within few days. Final digestion of carbohydrates by intestinal enzymes in the small intestine 1- Disaccharidases Location of their action: 1 Enzymes: 2 Source: The mucosal lining of the jejunum 2- α(1,6) Glucosidase (for branched oligosaccharides) Secreted by & remain associated with the luminal side of the brush border membranes of the intestinal Table is important Intestinal disaccharidases mucosal cells Enzyme Substrate Product Isomaltase isomaltose 2 Glucose Maltase maltose 2 Glucose Sucrase sucrose Glucose & fructose Lactase (β-galactosidase) lactose Glucose & galactose Digestion of Carbohydrates Dietary cellulose cannot be digested due to the absence of enzyme that can cleave β(1-4)bonds. It passes through the GIT largely intact. despite that, it has several beneficial effects Absorption of Monosaccharides by Intestinal Mucosal Cells Location: Duodenum & upper jejunum. Different monosaccharides have different mechanisms of absorption: Insulin: is NOT required for the uptake of glucose by intestinal cells. Absorption of digested carbohydrates 2 1 Facilitated diffusion (GLUT-mediated) Active transport (Energy-dependent): Co-transport with Na+ -Fructose is carried to enterocytes by GLUT5 -Glucose and Galactose are carried by SGLT1 and SGLT2 They are carried from enterocytes to live by GLUT2 Click here for the original picture Abnormal digestion of disaccharides (e.g. of lactose) In people who have lactose intolerance due to deficiency of Lactase, the GIT Normal flora utilizes lactose and causes the symptoms of intolerance like increase co2, diarrhea, distention, etc, Lactose intolerance (Lactase deficiency) Acetic acid & lactic acid are osmotically active ➝ pulling water to intestinal lumen Lactase (β-galactosidase) deficiency Undigested carbohydrate in large intestine osmotic diarrhea Bacterial fermentation of the undigested compounds in the large intestine CO2 , H2 gas abdominal cramps, diarrhea & distension (flatulence) Summary Protein Digestion Site secretions Activation of pancreatic enzymes ● The stomach ● The pancreas ● The small intestine Gastric secretions: ● HCL ● Pepsin. Pepsinogen is activated by: ● hydrochloric acid ● pepsin, i.e. autocatalysis Intestinal digestion: ● pancreatic enzymes (inactive zymogens) ● Intestinal aminopeptidase 1. Enteropeptidase Converts trypsinogen to trypsin. 2. Trypsin then activates all the other pancreatic zymogens (including itself): a. Chymotrypsin (endopeptidase) b. Elastase (endopeptidase) c. Carboxypeptidases (exopeptidases) Hormonal control ● Cholecystokinin (CCK) ● Secretin of digestion in small intestine Carbohydrates Digestion ● The mouth ● The intestinal lumen ● α-amylase ● Disaccharidases ● Isomaltase & a(1,6) glucosidase α-amylase: Normal level in serum: 25 -125 U/L significance: Diagnosis of acute pancreatitis Absorption of monosaccharides: 1. Facilitated diffusion (GLUT-mediate 2. Active transport (Energy-dependen Co-transport with Na 1. Cystinuria : Genetic errors in Cystine and dibasic amino acids transport. AbnormalIties 2. celiac disease : immune mediated damage to the villi of the small intestine in response to ingestion of gluten. Lactose intolerance Take home messages Proteolytic enzymes responsible for digestion of dietary proteins are produced by the stomach, the pancreas & the small intestine. The digestion of proteins in the stomach is the result of the action of HCl and pepsin. Pancreatic proteases are, like pepsin, synthesized and secreted as inactive zymogens. The intestinal digestion of proteins occurs in the small intestine’s lumen, on the luminal surface of the small intestine, and is completed intracellularly to produce free amino acids. In pancreatic insufficiency, the digestion and absorption of fat & protein is incomplete steatorrhea & appearance of undigested proteins in the feces. Salivary -amylase acts on dietary glycogen & starch in the mouth. Pancreatic -amylase continues the process of polysaccharide digestion in small intestine. The final digestive processes of carbohydrates into monosaccharides occur at the mucosal lining of the small intestine by disaccharidases & (1,6) glucosidase. Dietary cellulose cannot be digested due to the absence of enzyme that can cleave (1-4) bonds, so it passes through the GIT largely intact. Despite that, it has several beneficial effects. Absorption of the monosaccharides requires specific transporters (GLUTs). Lactose intolerance is due to deficiency of lactase enzyme and causes abdominal cramps, diarrhea & flatulence Quiz MCQs Q1: Humans can't absorb cellulose due to absence of? A- cellulose a-(1,4) glycosidase B- cellulose b-(1,6) glycosidase C- cellulose b-(1,4) glycosidase D- cellulose a-(1,6) glycosidase Q4: which one is a site for carbohydrates digestion? A- stomach B- pancreas C- small intestine D- mouth & intestinal lumen Q2: which hormonal release of watery solution rich in bicarbonate by pancreas? A- CCK B- secretin C- gastrin D- pepsin Q5: one of the following is normal of serum level of a-amylases? A- 24 B- 30 C- 129 D- 13 Q3: which enzymes convert trypsinogen to trypsin? A- trypsin B- elastase C- carboxypeptidase D- pepsin Q6: An 7 month old infant developed diarrhea and abdominal distention after breastfeeding , which of the following enzymes is deficient in this case ? A- lactase B- sucrase C- maltase D- amylase SAQ Q1:C | Q2:B | Q3:A | Q4:D | Q5:B | Q6:A Q1: Mention The source of proteolytic enzymes? 1- stomach 2- pancreas 3- intestine Q2: What are some of the effects of Cholecystokinin (CCK)? 1. Stimulates the release of pancreatic digestive enzymes 2. Stimulates the contraction of the gallbladder & release of bile (bile is used for lipids) 3. Decreases gastric motility → slower release of gastric contents into the small intestine (to give more time for the digestion) Q3: what amino acids transport is effected in cystinuria? Cystine, Ornithine, Lysine, Arginine “COLA or COAL” Members board Team Leaders Raghad Alhamid Remas Aljeaidi Mohammed Alqutub Team Members Leen Alduaij Zeyad Alotaibi Sultan Almishrafi Wafa Alakeel Mohammed Alarfaj Juwan Al Musma Madawi Alhussain Nazmi A Alqutub Wasan Alanazi Leen K Althunayan Faisal Alshowier Aishah boureggah Dana A Alkheliwi Osama Almashjari Mansour Alotaibi Aldanah Abdullah Nazmi M Alqutub Salma Alsaadoun Layan Al-Ruwaili Fahad Mobeirek Areej Alquraini Sarah Alajaji Waad alqahtani Special Thanks to Aleen Alkulyah for the Design! [email protected]