DIGESTION AND ABSORPTION OF CARBOHYDRATES – α-1,4 (GLYCANS) Maltooligosaccharides4 Major Classes of Carbohydrates – α-limit Dextrin • Monosaccharide – simple sugars – Brush Border Membrane (epitehlium of – Glucose duodenum and jejunum) – Fructose • Oligosaccharidases • Disaccharide – 2 monosaccharides – Lactase – Lactose → – Sucrose Glucose & Galactose – Lactose – Sucrase – Sucrose → • Oligosaccharide – few monosaccharides (cell Fructose & Glucose membrane) – Isomaltase (α- • Polysaccharide – polymer consisting of Dextrinase) – disaccharides and monosaccharides debranches α-limit – Starch Dextrin – Cellulose – Glucoamylase –Polysaccharides Maltooligosaccharides Plant → Glucose units Cellulose • PRODUCT: Glucose units Starch Amylope Amylose β-1,4 ctin Summary of Digestion of Carbohydrates α-1,4 α-1,4 α-1,6Digestion of Carbohydrates 1. Mouth – Salivary α-Amylase (Ptyalin) • Contained in the salivary secretions • Catalyzes the α-1,4 glycosidic bonds (linear) • PRODUCTS: – α-1,4 Maltose – disaccharide – α-1,4 Maltotriose – trisaccharide – α-limit Dextrin – branched oligsoccharides (α-1,4 and α-1,6)2. Stomach Absorption of Carbohydrates – No digestion of carbohydrates Transport – Gastric Acid (HCl) – inactivates salivary System α-amylase3. Small Intestine GLUT5 Sodium-Glucose – Pancreatic α-amylase (duodenum) Transport Transport • Contained in the pancreatic juice • Further catalyzes the α-1,4 Fructose Galactose Glucose glycosidic bonds • PRODUCTS: – Maltose – Maltotriose
Sodium-Glucose Transport – Goes to colon and enhances colonic • Active entry of Glucose and Galactose into the bacteria’s motility intestinal epithelial cells – stimulated by the – Symptoms: presence of Sodium in the lumen • Lactose intolerant • Membrane Protein • Intestinal distention – Transports Glucose, Galactose, and • Borborygmi – gurgling noises Sodium into the cell made by the intestine as It – 2 binding sites: mixes gas and liquid • Sodium-binding site • diarrhea • Sugar-binding site • Congenital Lactose Intolerance • Sodium – Infants who lack lactase have diarrhea – Pass through the large electrochemical when fed breast milk or milk formula potential gradient (made by sodium, containing lactose potassium-ATPase molecule in the basal – May result to dehydration and and lateral plasma membranes) electrolyte imbalance – Concentration and electrical forces – – Fed formula with sucrose or sucrose drives sodium into the cell instead of lactose – Transported by PRIMARY ACTIVE • Sucrase-Isomaltase Deficiency TRANSPORT – by the sodium-potassium – An autosomal recessive, inherited pump disorder • Glucose and Galactose – Intolerance to ingest sucrose – Goes against a concentration gradient • Glucose-Galactose Malabsorption Sydrome for the sugar – Hereditary – Energy released by the flow of sodium – Defect in the brush border sodium- to the electrochemical potential – glucose transport drives/forces glucose and galactose into – Ingestion of glucose, galactose, or the cell starch leads to flatulence and severe – Transported by SECONDARY ACTIVE diarrhea TRANSPORT – since it depends on the electrochemical gradient of sodium Digestion and Absorption of Protein • Exit – Via facilitated diffusion (or to some Digestion in the stomach extent, simple diffusion) Chief cells secrete inactive protein pepsinogen, – Glucose and Galactose leave the which is converted by hydrogen ions to the active intestinal epithelial cell at the basal and enzyme, pepsin. lateral plasma membrane Pepsin reduces only about 15% of dietary protein to – Diffuses into the mucosal capillaries amino acids and small peptidesGLUT5 Transport • Transports fructose across the enterocyte Digestion in the duodenum and small intestine (intestinal epithelial cell) Proteases • Via facilitated diffusion – because of high o secreted by pancreas concentration of fructose o plays a major role in protein digestionExtent of Absorption of Carbohydrates o Conducts proteolysis • 6%-10% of 20/60 grams of starch escapes o Important proteases: absorption in the small intestine – failure to Trypsin , Chymotrypsin, Carboxypeptidase A, absorb carbohydrate completely and, Elastase • Passed on the colon – Serves as an excellent carbon source for Digestion in the duodenum and small intestine colonic bacteria Enteropeptidase (enterokinase)Carbohydrate Malabsorption Syndromes o Secreted by mucosa of duodenum and • Lactose Malabsorption Syndrome jejunum – Deficiency of Lactase in the brush o Trypsinogen → Trypsin border Trypsin
o Acts autocatalytically to activate Not absorbed by humans to an extent that is trypsinogen nutritionally significant o Converts other proenzymes to the active Small amounts of luminal proteins are taken up by enzymes the Microfold cells (M cells) of the mucosal immune About 50% of ingested protein is digested and system (peyer’s patches) absorbed in the duodenum Absorption of small peptides Rate of transport of these small peptides usually exceeds the rate of transport of individual amino acids In experiments, glycine was absorbed by the human jejunum less rapidly as a single aminno acid than it was as diglycine or triglycine Single membrane transport system Responsible for the absorption of small peptides Brush borders of duodenum and small intestine ↑ affinity for dipeptides and tripeptides, contains peptidases very ↓ affinity for peptides of our or more These peptidases are integral amino acid residues. membrane proteins whose active sites Stereospecific – prefers L-amino acids face the intestinal lumen ↑ affinity or bulky side chains Proximal jejunum contains the highest Secondary Active Transport amounts of brush border enzymes Transport of dipeptides and tripeptides • These enzymes reduce the is powered by the electrochemical peptides produced by potential difference of H+ across the pancreatic proteases to membrane oligopeptidases and amino Jejunum more active in uptake of di- & acids. tripeptides Brush border peptidases: Most of small peptides are cleaved to Aminopeptidases – cleave single amino single amino acid in the cell and acids from the N terminals of peptides absorbed into blood as single amino Dipeptidases – cleave dipeptides to acid amino acids Absorption of Amino Acid Dipeptidyl aminopeptidases – cleave a Ileum is more active in the uptake of single amino dipeptide from the N-terminal end of a acid peptide. Brush border Basolateral membrane membraneSmall peptides and amino acids Transport Via specific amino Via different Small peptides and amino acids – principal products acid transport set of of protein digestion by pancreatic proteases and systems (into epith. transporters brush border peptidases cells) (out of epith. Small peptides (dipeptides, tripeptides, and Cells) tetrapeptides) Transporters Mostly unique to Occurs in • Produced in concentrations about epithelial cells many three to four times higher than epithelial cells those of single amino acids Transported across the brush border plasma Brush border & basolateral membrane membrane into intestinal epithelial cells • some transporters depends on the Na+ Small peptides then hydrolized by peptidases in the gradient, some transport systems are cytosol of the epithelial cells independent of Na+ • Simple diffusion as significant pathwayAbsorption of intact proteins and large peptides • The more hydrophobic the amino acid and the larger its concentration
gradient across membrane, the – Caused by a defect in either B0,+ or b0,+ greater importance of diffusion transporters in brush border membrane Brush border membrane in the epithelial Cells of small intestine o Na+ dependent and renal proximal tubule • amino acid uptake: secondary active Prolinuria - Defective renal and intestinal transport reabsorption of proline o Na+ independent – Defect in IMINO system in the epithelial • amino acid uptake: Facilitated transport brush border plasma membrane of the small intestine and renal proximal tubule – Hartnup’s disease, cystunuria, and Prolinuria do not result into malnutririon, because the epithelial cells are still capable of absorbing dipeptides and tripeptides INTESTINAL ABSORPTION OF WATER AND SALTS ABSORPTION OF WATER • Water absorption in the body generally takes place in the small intestines about 90% and 10% occurs at the large intestine • Movement of absorption is from blood to Basolateral membrane lumen and from lumen to blood o Na+ dependent - Mediate active uptake of amino acids. Provide amino acid for protein • About 2L of water is ingested daily about 7L are synthesis in the epithelial cells during present in daily gastrointestinal secretions and indigestive periods. about 100mL is lost daily during defecation o Na+ independent - Responsible for efflux of amino acids into the blood • In the duodenum, little water absorption occurs because water is added to chyme to bring about its isotonicity. Also, the duodenum is very permeable to water. • The jejunum is more active than the ileum in water absorption • Little absorption happens in the large intestines but it can absorb water against high osmotic pressure than the small intestine ABSORPTION OF Na⁺Defects of Amino Acid Absorption Hartnup’s disease - Rare hereditary disorder • Na⁺ is absorbed throughout the entire length of – Defective renal and intestinal transport the intestine of neutral amino acids – Caused by defects of B system of the • Movement of absorption is from blood to small intestine and the proximal renal lumen and lumen to blood tubule Cystinuria - Presence of cystine in urine • From the jejunum, the absorption of Na⁺ is greater then lessen as is reaches the colo
• It is greatest in the jejunum because if the • ENDOCRINE CONTROL OF ABSORPTION AND presence of glucose, galactose and neutral SECRETION amino acids – This is when hormones help in the absorption of • Na⁺ enhances absorption of sugars (glucose and water and salt galactose) and neutral amino acids vice versa – Mineralcorticoids,ROUTES OF INTESTINAL WATER AND SALT glucocorticoids,catecholamines,somatostatin,ABSORPTION enkephalins,aldosterone, opoids and ephinerphrine are hormones which help • TIGHT JUNCTIONS- the closely associated areas regulate absorption of salt and water of two cells whose membranes join together forming a virtually impermeable barrier to fluid • NEURAL REGULATION OF ABSORPTION AND SECRETION • Transcellular transport- port involves the transportation of solutes by a cell through a – ENTERIC NERVOUS SYSTEM cell. o Epithelial cells are innervated by the • Paracellular Transport - refers to the transfer of secretomotor neurons which stimulates substances between cells of an epithelium net secretion. • Villous Cells- projections found at tips of special – PARASYMPATHETIC NERVOUS SYSTEM epithelial cells which helps in absorption o The enteric nervous system is • Crypt Cells- are found in less differentiated cells innervated by the parasympathetic which produces net secretion of water and ions fibers. The parasympathetic nervous system help in diminishing absorptiveMECHANISM OF WATER ABSORPTION fluxes and enhance secretions • It depends on the absorption of sodium and – SYMPATHETIC NERVOUS SYSTEM chloride ions o Stimulation of sympathetic fibers • In the small intestine, absorption of water stimulate net absorption. occurs in the absence of osmotic pressure between the luminal contents and intestinal o It is related to the enteric nervous capillaries system in a way that the sympathetic fibers stimulate the enteric nerve fibers • In the colon. Water absorption occurs against an osmotic pressure gradient. It is known as • REGULATION OF ABSORPTION AND SECRETION standing gradient osmosis which is when the BY THE GASTROINTESTINAL IMMUNE SYSTEM lateral intracellular spaces are large and swollen. When fluid transport is blocked, – There are various mediators which enhance net intercellular spaces almost disappear secretion of water and electrolytes • Absorption of sugars and amino acids allows – Mediators include histamine, serotonin, prostaglandin, thromboxanes, leukotrienes, more water to be absorbed platelet-activating factor,adenosine, reactivePHYSIOLOGICAL REGULATION OF SALT AND WATER oxygen species, nitric acids and endothelinABSORPTION – These mediator works in two ways
– Directly affect intestinal epithelial cells and ABSORPTION OF CALCIUM either stimulate or inhibit absorption CALCIUM IONS o Act on enteric neurons to increase -Absorbed by all segments of the intestine. -Forms insoluble salts with many anions present activities in secretomotor circuits in food (phytate, phosphate, oxalate)PATHOPHYSIOLOGICAL ATERATIONS OF SALT AND These salts are soluble at low pH.WATER ABSORPTION INTESTINAL ABSORPTION OF CALCIUM • DEFICIENCY OF A NORMAL ION TRANSPORT Ability of intestine to absorb Ca2+ is regulated SYSTEM (lowCa diet = increase ability to absorb) (highCa diet = less to absorb) – Congenital chloride diarrhea Stimulated by Vitamin DThe chloride and bicarbonate exchange transport Parathyroid hormone- stimulates intestinal absorptionsystem in the brush plasma border of the ileum and of Calciumcolon is missing or deficient HOW?? *it promotes the release of the active form ofIt impairs the chloride absorption which leads to Vitamin D from the kidney.diarrhea with stools having a high chlorideconcentration Cellular Mechanism of Calcium Absorption • ABNORMAL ABSORPTION OF A NUTRIENT 1. Ca2+ crosses the brush border plasma membrane via Ca2+ channels – Carbohydrate malabsorption 2. Calbindin binds to Ca+ syndromes wherein sugar is retained in the lumen of the small intestine WHAT IS CALBINDIN?? increases the osmotic pressure in the -it’s a protein lumen. -also known as intestinal calcium binding proteins (CaBP). – As a result, water is also retained and -allow large amounts of Ca2+ to traverse the cytosol chyme increases in volume which is -prevents concentrations of free Ca2+ ions to form then passed on to the colon. Increased insoluble salts with intracellular anions. chyme content in the colon impairs its 2 forms of Calbindin ability to reabsorb electrolytes leading *Calbindin D9k-binds two Ca2+ ions to diarrhea *Calbindin D28k-binds 4 Ca2+ ions • HYPERMOTILITY OF THE INTESTINE 3. Ca2+ is extruded across the basolateral membrane by Ca2+-ATPase and Na+ - Ca+ exchange mechanism. – Its when the peristaltic movement of the intestine is great thus it cannot What is Ca2+-ATPase and Na+ - Ca+?? absorb the maximum amount of Ca2+ - ATPase nutrients from the ingested food -Primary active transport -It splits ATP and uses the energy to transport • ENHANCED SECRETION OF WATER AND Ca ELECTROLYTES -use when intracellular concentrations are low – It is when the intestines secrete too Na+ - Ca2+ exchanger much water that the intestinal -Uses energy of the Na+ gradient to extrude absorption cannot cope up. Ca2+ by secondary active transport -use when intracellular concentrations are high
->Insoluble complexes are more soluble to low pH.ACTIONS OF VITAMIN D Therefore hydrochloric acid (HCl) enhances iron absorption.Vitamin D- essential for normal levels of calciumabsorption. (*so if someone has a deficiency in acid secretion iron*it stimulates each phase of absorption: absorption would be low) -passage across the brush border membrane. -traversal of the cytosol. What promotes iron absorption? -active extrusion across the basolateral ASCORBATEmembrane. -Ascorbate forms a soluble complex with iron,- By binding to nuclear receptors stimulating the preventing iron from forming insoluble complexes.synthesis of messenger RNA -reduces Fe3+ and Fe2+.-Stimulating synthesis of Calbindin-D9k and Calbindin- (Fe2+- absorbed much better that Fe3+ becauseD28K its tendency to form insoluble complexes is much lesser-Increasing the level of brush border associated than the Fe3+)Calbindin.-Increasing the level of the basolateral Ca2+-ATPASE HEME IRON -Well absorbed.Vitamin D deficiency -Release by proteolytic enzymes from proteinsRICKETS in the intestinal lumen. -a condition where in the rate of absorption ofCa2+ is very low, causing low amount of Ca2+ available Ironfor bone growth. - is absorbed by villus enterocytes in the proximal duodenumIn children with rickets, bone growth is abnormal. -Efficient absorption requires an acidic WHY? environment, and antacids. There is a failure to deposit normal amounts of Cellular Mechanism of Iron Absorptioncalcium salts in the bone matrix, bones are softer andmore flexible than normal. These changes contribute to 1. Ferric iron (Fe+++) in the duodenal lumen is“bow- legged” appearance of children with rickets. reduced to its ferous form through the action of brush border ferrireductase.MALABSORPTION OF CALCIUM 2. May occur to those who have bowel disease 2. Iron is co-transported with a proton into theand disorder such as enterocyte via the divalent metal transporter (DMT-1). *Gluten enteropathy *when inside may follow 2 major pathways *Tropical sprue which depends on a complex programming of cell. -diminishes the surface area of the brush 3. Following of pathways..border. *Iron abundance states:ABSORPTION OF IRON -iron within the enterocyte is trapped by incorporation into ferritin and hence, notIron absorption is limited.. transported into blood. WHY?? *it forms insoluble salts with anions, such ashydroxide, phosphate, and bicarbonate that are present *Iron limiting states:in intestinal secretions. - iron is exported out of the enterocyte via a transporter (ferroportin). It then binds *it forms insoluble complexes with other to the iron-carrier transferrin for transport throughoutsubstances commonly present in food such as phytate, the body.tannins, and fiber of cereal grains. Regulation of Iron Absorption
-Iron absorption is regulated in accordance with lipids are slightly soluble in water, each stage ofthe body’s need for iron. their processing poses special problem to the Example: gastrointestinal tract. In chronic iron deficiency or after hemorrhage, The digestion product of lipids from smallduodenum and jejunum increase their capacity to molecular aggregates known as micelles withabsorb iron. the bile acids. The digestion and absorption of lipids are moreIron overload complex than for any other class of nutrients and are more frequently subject to malfunction. -Absorption of more iron than needed. -Can result from chronic ingestion of largeamounts of absorbable iron. Digestion of lipids in stomach*(common in African tribes that consume brewed beer Significant hydrolysis of triglycerides occurs inwith high iron content) stomach. The enzymes are responsible for lipid hydrolysisIdiopathic hemochromatosis in stomach are known as preduodenal -genetic disorder lipasses,the enzymes operate most effectively -excessive amount of iron is absorbed at acids PHs. in rates, principally preduodenalfrom the diet that is normal in iron content. lipase is lingual lipase, which is produced by -is some cases there are increased glands under the circuvallate papillae of thelevels of the ion transport proteins tongue.DCT1 and IREG1.Absorption of Magnesium Digestion of lipids in the duodenum and jejunum Absorbed in the entire length of intestine butthe largest Magnesium absorption takes place in the Pancreatic lipolytic enzymes.ileum. Pancreatic juice contains the major lipolytic enzyme responsible for digestion of lipids.Absorption of Phosphate The most important digestive enzyme are glycerol ester hydrolase ,colipase ,cholesterolJejunum is responsible for the largest ester hydrolase and phospholipase A, How is it absorb?? The arrival of lipids in the duodenum causes *phosphate crosses the brush border secretion of bile and fat is emulsified by bile saltplasma membrane by Na+-powered secondary active micelles.transport. Then it leaves the cell by moving down to its Pancreatic lipase hydrolyzes triglycerides to freeelectrochemical potential gradient across a basolateral fatty acids and monoglycerides.membrane by means of facilitated transport. Phosphate A breaks down phospholipids into fatty acids and lysolecithin.Absorption of Copper Then free faty acids, monoglycerides, and lysolecithin leaves micelles and enter theWhen dietary copper is low the ingested copper that is epithelial cells then they are resynthesized intoabsorbed increases. triglycerides and phospholipids. These combine to form chylomicrons. ThenIndividuals who fail to secrete sufficient amounts of when the combine into the blood, they becomecopper in the bile, the body’s copper pool grows and apolipoprotein, which allow them to bind tocooper accumulates in certain tissues. receptors on capillaries in muscle and fat.Digestion and absorption of lipids Cytosilic lipid transport protein The primary lipids of a normal diet are triglycerides. The diet contains smaller amount Handling of lipids inside the intestinal epithelial of sterol, esters, and phospholipids. Because Proteins bind cholesterol and other sterols.
Two classes of fatty acid-binding proteins exist in the cytosol of epithelial cells of upper intestine I-FABP & L-FABP Two isoforms of sterol carrier protein SCP-1 & SCP-2Resynthesis of lipids in the smooth endoplasmicreticulum The products of lipid digestion are carried by the binding proteins to the smooth endoplasmic reticulum The intestinal epithelial cells are also capable of some synthesis of new lipids.Absorption of bile acids Bile is a complex fluid containing water, electrolytes and a battery of organic molecules including bile acids, cholesterol, phospholipids and bilirubin that flows through the biliary tract into the small intestine These are absorbed largely in the terminal part of the ileum.Malabsorption of lipids Malabsorption is a clinical term that encompasses defects occurring during the digestion and absorption of food nutrients by and infections of the gastrointestinal tract. Among the general causes of lipid Malabsorption are bile deficiency, pancreatic insufficiency, and the intestinal mucosal atrophy that occurs in some disease states.