Digestion, Transport, and Absorption of Nutrients PDF

Digestion, Transport and Absorption of Nutrients Dr. Önder Şirikçi  Digestion The breakdown of naturally occurring foodstuffs into assimilable forms Proteins amino acids Carbohydrates monosaccharides Triacylglycerols fatty acids + glycerol Minerals...

Digestion, Transport and Absorption of Nutrients Dr. Önder Şirikçi  Digestion The breakdown of naturally occurring foodstuffs into assimilable forms Proteins amino acids Carbohydrates monosaccharides Triacylglycerols fatty acids + glycerol Minerals and vitamins are also made more assimilable. 3 phases: neurogenic, gastric, intestinal  Digestion The breakdown of naturally occurring foodstuffs into assimilable forms Minerals and vitamins are also made more assimilable.  Digestion in the Oral Cavity Salivary glands: parotid, sublingual, submaxillary (the latter give most of the secretion) Acinar cells secrete fluid that is close to the plasma in its composition (Na+, K+, Cl-, HCO3-) Duct cells modify the ionic contents by extracting Na+ and Cl- As a result saliva is; rich with K+, HCO3-, hypotonic, contains salivary amylase, lingual lipase, lysozyme and mucin Parasympathetic stimulation increases the release of watery saliva  Digestion in the Oral Cavity Saliva aids in mastication & swallowing a medium where food molecules can dissolve and hydrolases can act on foodstuffs by increasing solubility and surface area a vehicle for excretion of certain drugs (ethanol, morphine), ions (K+, Ca2+, HCO3-, SCN-, I-) & immunoglobulins Significance in digestion is small (short acting time). Inactivated below pH 4 in the stomach Lingual lipase is not significant in humans  Digestion in the Stomach Sight, smell & taste of food stimulate cerebral cortex & vagal nuclei, which in turn stimulate gastric parietal & chief cells Gastric Secretions: Gastrin, HCl & H2O Pepsin Rennin Gastric Lipase Mucin, inorganic salts HCl Secretion by the Stomach Gastric acid secretion is controlled by three mechanisms: Neurocrine (vagus/local reflexes) Endocrine (gastrin) Paracrine (histamine)  Cell Types in the Gastric Mucosa gastric crypts HCl Secretion by the Parietal Cell H secretion: active transport against x 106 gradient K H2O Stomach pH7.4 HCO3 alkaline tide: alkaline urine after a meal  Carbonic Anhydrase Reaction CA CO2 + H2O H2CO3 HCO3- + H+ Carbonic Anhydrase Enzyme  Gastric Secretions Pepsin: Produced by chief cells as the inactive precursor (zymogen) Pepsinogen Pepsinogen is converted to Pepsin via hydrolytic cleavage of a peptide by HCl. Pepsin can rapidly activate other pepsinogens (autocatalysis) Pepsin is an endopeptidase (peptide bonds adjacent to Glu, Phe, Tyr, Trp, Leu). Most effective on collagen Peptides and carbohydrates are broken down by enzymatic hydrolysis Digestion of Proteins Digestion of Proteins  Gastric Secretions Rennin: Absent in adults, important in infants Changes the casein of milk to paracasein in the presence of Ca2+, which can then be hydrolyzed by pepsin Intrinsic Factor: Only essential function of stomach Produced by parietal cells Required for vitamin B12 absorption Intrinsic factor/B12 complex absorbed from ileum Defect Pernicious Anaemia  Gastric Secretions Gastric Lipase: TG FFA + 1,2 DAG Produced by chief sells More important in the neonatal period when the pancreatic lipase may be low in activity Destroyed at low pH, but active after feeding 30 % of TG can be digested in 2-4 hours Short & medium chain FA can be absorbed via the stomach wall; longer chain FA dissolve in lipid droplets Fat digestion Emulsification- breaking up large lipid droplets so that enzymes can digest them. Enzymatic digestion (hydrolysis) of triglycerides- pancreatic lipase Micelle formation-hydrolysis products form with bile salts to make micelles. FAs and glycerol and monogycerides absorbed.  Digestion in the Intestines Chyme intermittently passes on to the duodenum Pancreatic & biliary secretions are alkaline and neutralize the pH, pepsin is inactivated Bile acids and salts are amphophilic; reduce surface tension Bile emulsify fats & enable absorption of fat soluble vitamins, neutralize chyme and serve to excrete cholesterol, bile pigments & drugs  Pancreatic Secretions Which of the pancreatic enzymes of blown needs to be cleared to be activated? Zymogen Active Enzyme Substrate Chymotrypsinogen Chymotrypsin Peptides Trypsinogen Trypsin Peptides Proelastase Elastase Peptides Procarboxypeptidase Carboxypeptidase Peptides (A,B) (A,B) Prophospholipase A2 Phospholipase A2 Phospholipids Lipase Triglycerides Amylase Starch, Glycogen Ribonuclease RNA Deoxyribonuclease DNA  Zymogen Activation Common activator (Lys 6 – Ile7 of Trypsinogen) Basic a.a. Uncharged aromatic a.a. C terminal exopeptidase Proelastase Elastase Small a.a; Gly, Ser, Ala Pancreatic Secretions: Amylase Amylase: Digestion of Carbohydrates  Amylase Acting at random locations on the starch chain, α-amylase breaks down polysaccharides, yielding either maltotriose and maltose from amylose, or maltose, glucose and "limit dextrin" from amylopectin. They belong to glycoside hydrolase family α-amylase β-amylase γ-amylase Animals, plants, Animals, Source Plants, microbes microbes microbes Tissue Saliva, pancreas Seeds, fruits Small intestine Random α-1,4 Second α-1,4 Last α-1,4 Cleavage site glycosidic bond glycosidic bond glycosidic bond Reaction Maltose, dextrin, Maltose Glucose products etc Optimum pH 5.6–5.8 5.4–5.5 4.0–4.5 Carbohydrate Digestion Intestinal mucosal cells Disaccharidases Brush border enzymes Maltase Sucrase - isomaltase (bifunctional enzyme) Lactase Trehalase In most mammals, including humans, lactase activity starts to decrease after weaning and is almost completely lost after adolescence, leading to lactose intolerance.  Pancreatic Secretions: Lipase Pancreatic lipase, catalyzes hydrolysis of triacylglycerols at C position 1 & 3, forming 1,2-diacylglycerols, & then 2-monoacylglycerols (monoglycerides). Bile salts, Co-lipase, phospholipids & phospholipase A2 are required for the enzyme to act at the lipid-water interface. Lipase is actually inhibited by bile salts. Co-lipase overcomes this inhibition by binding lipase in a 1:1 molar ratio and also anchoring to the bile salt covered TG  Pancreatic Secretions: Lipase O O H2C O C R1 H2C O C R1 O O O HC O C R2 H2O HC O C R2  O C R3 O H2C O C R3 H2C OH triacylglycerol 1,2-diacylglycerol fatty acid Less than 25 % of TG is hydrolyzed to FFA + Glycreol 75 % is hydrolyzed to FFA + 2-monoacylglycerol Pancreatic Secretions: Phospholipase A2 Lysophospholipids, the products of Phospholipase A2 reactions, are powerful detergents  Bile Functions Constituents Emulsification of lipids Water (97%) Activation of enzymes for Bile Salts digestion of lipids Bile Pigments (Bilirubin Conjugation of bilirubin to and Biliverdin) form a water soluble product Unesterified cholesterol for excretion Inorganic Salts Excretion of cholesterol Fatty Acids Excretion of drugs, heavy Lecithin metals, and environmental toxins Neutralization of acid delivered to duodenum from stomach  Bile Acids Synthesized from cholesterol (only breakdown product of cholesterol)  Regulation of bile acid production is a determinant of cholesterol homeostasis Because of the both polar and nonpolar regions, they can align at lipid-water interfaces and reduce surface tension (detergents). Solubilize biliary lipids (cholesterol and phospholipid excretion) and dietary lipids (digestion) by forming micelles. Amphopilic Property of Bile Acids  Synthesis of Bile Salts Hydroxylation Cytochrome P-450/microsomal monooxygenase system 7--hydroxylase is rate limiting Side chain cleavage Conjugation (increases solubility) Secondary bile acids Intestinal bacterial modification Deconjugation Dehydroxylation  Deoxycholic acid  Lithocholic acid  Bile Acid Synthesis 7-Hydroxylase Cholesterol 7-Hydroxycholesterol Liver 12 -Hydroxylase Cholic acid Chenodeoxycholic acid Glycine Taurine Glycine Taurine Cholate Chenodeoxy... 7-Hydroxy 38 % 34 % Glycocholic acid Taurocholic acid Glycochenodeoxycholic acid Taurochenodeoxycholic acid Bacterial Transformation Intestine Deconjugation 7-dehydroxylation Deoxy... Litho... 28 % Deoxycholic acid Lithocholic acid 1-2 % Enterohepatic circulation Feces  Lacks 12  hydroxyl Chenodeoxycholic acid Glycochenodeoxycholic acid Taurochenodeoxycholic acid  Nomenclature Primary bile acids Cholic and chenodeoxycholic acids Bile salts Glycine and Taurine conjugates (ionized) Glycine conjugates predominate 3-4:1 Secondary bile acids Deoxycholic acid and lithocholic acid  Enterohepatic Circulation Bile salts are reabsorbed in the terminal ileum Efficient; 98-99 % of secreted bile acids return to liver. A small pool of 3-5 g is cycled 6-10 times/day Lithocholic acid is insoluble and not reabsorbed. 500 mg/day is eliminated in feces 1-2 % /pass (major pathway for elimination of cholesterol. To compensate, an equal amount is synthesized from cholesterol Regulation of Bile Acid Synthesis 7--hydroxylase is feedback regulated by Farnesoid X Receptor (FXR) When the size of the bile acid pool in enterohepatic circulation increases, FXR is activated and transcription of the gene coding the enzyme is suppressed. Activity of the enzyme is stimulated by cholesterol Glands In The Small Intestine Brunners glands (duodenal glands) Found only in duodenum, watery mucous secretion Crypts of Lieberkuhn Secrete lots of water, and bicarbonate Brush border mucous and digestive enzymes- peptidases, enterokinase, lipases, disaccharidases Secretions in the GI Tract  Intestinal Secretions Aminopetidase Polypeptides small peptides, a.a. at N-end Dipeptidase Dipeptides amino acids Sucrase Sucrose fructose + glucose Maltase Maltose glucose + glucose Lactase Lactose glucose + galactose Trehalase Trehalose glucose Phosphatase Organic Phosphates free phosphate Isomaltase Isomaltose glucose Polynucleotidase Nucleic acids nucleotides Nucleosidase Nucleosides purine pyrimidine base + pentose P Absorption in Small Intestine All nutrients pass through epithelial cells. Tight junctions prevent movement between cells Amino acids transported through membrane & into blood capillaries. Monosaccharides transported through membrane & into blood capillaries. Fatty acids & monoglycerides: Transported through membrane & reassembled into triglycerides. Triglycerides coated with proteins to form chylomicrons. Chylomicrons transported to lymphatic capillaries (lacteal). Digestion and Absorption of Carbohydrates Glucose intake Na+ cotransport Na+ independent intake Diffusion Absorption of Monosaccharides SGLT-1 Carrier mediated diffusion  Digestion and Absorption of Proteins The L- isomers (but not D-) of amino acids are actively transported This process is energy dependent and requires pyridoxal phosphate (B6) Various transporters have been identified Neutral a.a. carrier Na+ dependent Phe, Met carrier Imino acid carrier Neutral or lipophilic a.a Na+ independent Digestion and Absorption of Proteins  Lipid Absorption Intestinal epithelial cells synthesize triacylglycerols, cholesteryl esters, phospholipids, free cholesterol, and apoproteins, and pack them into chylomicrons. FFA>10 C are found esterified in the lymph FFA