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Pancreatic lipase hydrolyzes TGs to monoglycerides (MG) and FFA; procolipase is also secreted and is activated in the lumen of theduodenum by trypsin, forming colipase, which facilitates the enzymatic action of pancreatic lipase; cholesterol ester hydrolase hydrolyzes cholesterol esters tocholesterol and FFA; phospholipase A2 hydrolyzes PL tolysophospholipids and FFA. These cleavage products areall able to diffuse into the enterocytes; however, theymust first be incorporated into micelles to traverse theunstirred water layer.295and exposed to pancreatic lipases.
However, although thepancreatic lipase can readily hydrolyze triglycerides, lipaseaccess to lipids is blocked by bile. The colipase is critical forlipase action. It displaces the bile from the lipids, allowing thelipase to hydrolyze the lipids.These are the steps for micelle formation (Fig. 25.4):1. The detergent action of bile emulsifies the fat globules,forming smaller fat droplets, which increases the surfacearea for digestion.2. Colipase displaces the bile from the lipids.3.
Pancreatic lipase binds to colipase and hydrolyzes theTGs to monoglycerides and FFA. Cholesterol esterhydrolase and phospholipase A2 hydrolyze cholesterolesters and phospholipids (these enzymes are not affectedby bile).4. When there is a critical amount of bile and digestedlipids, they form a micelle, with the hydrophilic ends ofbile salts on the outside, and lipophilic ends inside surrounding the lipid products.5. The micelles diffuse through the unstirred water layerto the enterocytes, and the lipids are released from themicelle and diffuse through the enterocyte membrane,leaving the bile salts in the lumen.6.
The bile salts continue down the small intestine to theterminal ileum, where most primary bile salts enter theintestinal cells through Na+-dependent transporters.The bile diffuses out of the cell into the portal circulation back to the liver.Intracellular Lipid ProcessingOnce the lipids diffuse into the enterocytes, they are re-esterified with FFA in the smooth endoplasmic reticulum to reformtriglycerides, cholesterol esters, and phospholipids (seeFig. 25.4). The lipids are surrounded by a β-lipoprotein(ApoB) coat forming chylomicrons.
The chylomicrons arepackaged into secretory vesicles and leave the cell by exocytosis. The chylomicrons enter the lymph lacteals; they are toolarge to enter capillaries. They enter the systemic blood inthe large vessels in the thorax, and return to the liver forprocessing through the systemic circulation. A small amountof short-chain fatty acids are not incorporated into chylomicrons and are able to diffuse into the portal blood to the liver.This is a minor pathway.Micelle FormationMicelles are aggregates of bile salts and small lipids. The polar(hydrophilic) ends of the bile are oriented outward, and thehydrophobic core allows incorporation of small lipids.
Themicelles function to move lipids through the unstirred waterlayer, allowing lipids access to the enterocytes.Most lipids are in the last portion of chyme entering the smallintestine. In the duodenum, the lipids are surrounded by bileb-Lipoprotein is critical for chylomicron formation.When it is absent, lipids will not be able to exit theintestinal cells and enter the lymph. Fat builds up in the enterocytes. As the villous cells are replaced and sloughed off into thelumen, the lipid is excreted. This condition of abetalipoproteinemia results in the inability to absorb lipids.296Gastrointestinal PhysiologyKEYTriglycerides (long and short chain)Diglycerides (long and short chain)Monoglycerides (long and short chain)Fatty acids (long and short chain)CholesterolCholesterol estersGlycerolCaroteneNa, KMg, CaPancreasiceatic juIntestinal wallIntestinallipaseGlycocalyxSolubleInsolubleHydrolysis(partial orcomplete)icellesPancreaticlipaseole nCh initokcysinretS ecPancreBileMEmulsionTo liverTo systemiccirculation viathoracic ductLymphaticsPortal veinChylomicronMicrovilliEpithelial cellFigure 25.4 Lipid Digestion and Absorption Although some lipid digestion occurs preduodenallyby lingual and gastric lipases, most digestion occurs in the lumen of the small intestine by pancreatic lipase.The overall process of digestion and absorption is complex, because the lipids must first be incorporatedwith bile into micelles and shuttled through the unstirred water layer to the enterocytes.
The lipids diffuseinto the enterocytes and are re-esterified with free fatty acids in the smooth endoplasmic reticulum andpackaged into chylomicrons for transport into the lymph, eventually passing through the thoracic duct intovenous circulation. Some soluble fats (glycerol and short-chain and medium-chain fatty acids) can accessthe enterocytes without micelles and are small enough to be taken up into the portal circulation.ELECTROLYTE AND WATER ABSORPTIONIn addition to the ∼2 liters (L) of fluid ingested each day,approximately 7 or more additional liters are added to the GItract in various segments to facilitate digestion and absorptionof the nutrients. Absorption of the 9 L of fluid occurs as nutrients and electrolytes are absorbed. Within the small intestine,several mechanisms of absorption occur in various segments(Fig.
25.5):■■Jejunum: The large surface area in the small intestinemakes digestion and absorption extremely efficient.The bulk of the nutrients, fluid, and electrolytes isabsorbed by mid- to late-jejunum, although thereis significant electrolyte and fluid absorption in theileum.Sodium absorption is a driving force for nutrient andwater absorption, and the basolateral Na+/K+ ATPaseDigestion and Absorption297A. JejunumAminoacids,glucose3Na+ATPNa+2K+Na+2Cl–K+Cl–Na+HCO3–+ H+H+H2CO3CO2H2OB.
IleumAminoacids,glucose3Na+ATPNa+2K+Na+Figure 25.5 Electrolyte and Fluid Transport A, Sodiumabsorption in the jejunum and ileum occurs though a variety of mechanisms, with sodium movement facilitating entry of other molecules suchas glucose, galactose, amino acids, and chloride. This also creates anosmotic gradient for water absorption. B, The ileum secretes HCO3− intothe gut lumen in exchange for Cl−, and the Cl− exits through the basolateral membrane by facilitated transport. C, The colon is sensitive tothe effects of aldosterone, which will enhance sodium absorption andpotassium secretion. The water follows the osmotic gradient, dehydrating the chyme and producing feces.2Cl–K+Cl–Na+H+Cl–CO2+H 2OCAHCO3–C. ColonNa+3Na+ATP2K+K+Cl–CO2 + H2OCl–CAHCO3–Na+H+298■■■Gastrointestinal Physiologymaintains the low intracellular concentration necessaryfor the lumenal Na+ to enter the cells.Bicarbonate is formed by the intracellular CO2 metabolism and exits the cell through the basolateral membraneby facilitated transport.
The water follows the osmoticgradient created by the electrolyte movement (seeFig. 25.5A).Ileum: As noted, the Na+-dependent transporters forsugars and amino acids are also present in the ileum, andthis redundancy helps ensure nutrient absorption ifabsorption is reduced in the jejunum. Sodium isabsorbed in the same manner as in the jejunum; however,in the ileum and colon, the bicarbonate formed in thecells is secreted into the lumen via HCO3−/Cl− antiporters, and the chloride leaves the basolateral side via facilitated transport (see Fig.
25.5B).Colon: Aldosterone stimulates lumenal sodium absorption by Na+/K+ and Na+/H+ exchangers. As water followsthe sodium, the chyme is dehydrated, producing feces.The colon usually absorbs ∼400 to 500 milliliters ofwater per day, which follows sodium absorption, andwater absorption in the colon can increase to ∼1 L perday, when aldosterone is elevated (see Fig. 25.5C).A. Ca2+LumenCa2+Ca2+ATPCa2Ca2+Calbindin3Na+VitaminD3B. IronHemin(Fe3+)Hemin (Fe3+)Fe2+Fe3+DIVALENT CATION ABSORPTIONCalcium and iron are absorbed early in the small intestine,from the duodenum through early- to mid-jejunum (first halfof the jejunum).
Because the early part of the small intestinehas a lower pH, it favors the reduced (Fe2+) form of iron andkeeps the cations from forming insoluble salts.Ferritin(storage)Fe3+TFFe2+FRHFe2+Fe2+DMT1Fe3+IREG1CalciumCalcium absorption is regulated by active vitamin D(1,25-dihydroxycholecalciferol), which increases the calciumchannels (TRPV-6) at the lumenal membrane, as well as thecytosolic binding protein calbindin. Calbindin binds Ca2+,keeping the intracellular free Ca2+ levels very low (10−6 M),maintaining a gradient for Ca2+ entry into the cell, and allowing Ca2+-dependent messenger systems to function properly.The Ca2+ exits the basolateral side through active Ca2+ ATPasepumps and Na+/Ca2+ antiporters (Fig. 25.6A).
The activity ofthe Ca2+ ATPase is also increased by vitamin D.Figure 25.6 Calcium and Iron Absorption A, Calcium enteringthe enterocytes through the TRPV-6 Ca2+ channel is bound by cytosoliccalbindin. Transport out of the cell is via Ca2+ ATPase pumps and Na+/Ca2+ exchangers. Active vitamin D enhances Ca2+ absorption by increasing calbindin production and Ca2+ pump activity. B, Ingested iron is inboth organic (heme) and inorganic forms. Heme can enter enterocytes,and intracellular heme oxygenase releases the iron (Fe2+), which is thenbound in ferritin stores or shuttled out of the cell through the transmembrane protein hephaestin (H) and bound to transferrin (TF) in the blood.It is transported to the liver for storage, or the bone marrow for hemoglobin and red blood cell production. Inorganic iron in the ferric form(Fe3+) can be reduced to Fe2+ by ferrireductase (FR) in the lumenal membrane, and then the Fe2+ can enter the enterocytes through the divalentmetal transporter 1 (DMT-1), and be handled as described above.IronFree iron is toxic to cells, and in the body iron is alwaysbound to proteins.
Ingested iron is either in organic (hemoglobin or myoglobin from meats) or free (from vegetables)forms.Organic forms can diffuse into the enterocytes, and intracellular xanthine oxidase frees the iron, which is then bound inferritin in the cell or is transported out of the cell into theblood, where it is bound to transferrin (TF).The lumenal membranes in the jejunum have divalent metaltransport proteins (DMT-1), which transport free Fe2+ intothe cell, where it is bound in ferritin. The iron can also betransported out of the cell into the blood, where it is boundto transferrin (TF) (see Fig.
25.6B).In the blood, the transferrin-bound iron is transported to thebone marrow for hemoglobin and red blood cell synthesis, orDigestion and AbsorptionTable 25.2299Vitamin AbsorptionB12VitaminSite of AbsorptionIFMechanismWATER SOLUBLE VITAMINSB12-IF+Vitamin CIleumNa -coupled/2° activeThiamin (B1)JejunumNa+-coupled/2° activeTCIIB12-IFB12+Riboflavin (B2)JejunumNa -coupled/2° activeBiotinJejunumNa+-coupled/2° activeVitamin B12IleumFacilitated diffusionPyridoxine (B6)Jejunum and ileumPassive diffusionFAT-SOLUBLE VITAMINSB12Vitamin B12Vitamin AJejunum and ileumPassive diffusionVitamin DJejunum and ileumPassive diffusionVitamin EJejunum and ileumPassive diffusionVitamin KJejunum and ileumPassive diffusionFigure 25.7 Vitamin B12 Absorption Vitamin B12 (cobalamin) isprotected from digestion in the small intestine by binding to intrinsicfactor (IF) released from the gastric parietal cells.
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