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Section 10 2. Digestion & absorption of lipids 1/6/06.

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Presentation on theme: "Section 10 2. Digestion & absorption of lipids 1/6/06."— Presentation transcript:

1 Section Digestion & absorption of lipids 1/6/06

2 Brief review of some basics digestion role: convert foods into absorbable form digestion role: convert foods into absorbable form catalysts: hydrolases, usually requiring activation catalysts: hydrolases, usually requiring activation absorption role: transfer nutrients from lumen to blood/lymph absorption role: transfer nutrients from lumen to blood/lymph cotransport (symport), facilitated transport, diffusion cotransport (symport), facilitated transport, diffusion

3 Digestion of fats only fatty acids & monoglycerides are absorbable only fatty acids & monoglycerides are absorbable products of lipase action on main dietary lipids, triglycerides* nonpolarity of lipids results in large particles with most molecules not on surface: oil phase nonpolarity of lipids results in large particles with most molecules not on surface: oil phase examples:particle size fraction of molecules on surface 1 mm ~ 4/10 6 (~ 4 ppm) 1 μm ~ 4000 ppm 1 μm ~ 4000 ppm result: most molecules inaccessible to digestive enzyme, lipase result: most molecules inaccessible to digestive enzyme, lipase effective digestion produced by effective digestion produced by dispersion of particles: peristalsis, surfactants dispersion of particles: peristalsis, surfactants anchoring of enzyme to particles anchoring of enzyme to particles *aka triacylglycerols 1 slide 9

4 Lipids & amphiphiles lipids: organic substances not soluble in H 2 O lipids: organic substances not soluble in H 2 O structurally largely or completely hydrocarbons, therefore mainly nonpolar structurally largely or completely hydrocarbons, therefore mainly nonpolar amphiphiles (amphipaths): lipids with both polar & nonpolar parts amphiphiles (amphipaths): lipids with both polar & nonpolar parts more polar amphiphiles are surfactants (detergents) more polar amphiphiles are surfactants (detergents) interact with polar (e.g., H 2 O) & nonpolar structures interact with polar (e.g., H 2 O) & nonpolar structures bind at H 2 O-oil interface bind at H 2 O-oil interface results of binding: surface of particles (e.g., oil drops) made more polar surface of particles (e.g., oil drops) made more polar oil phase dispersed into emulsion droplets oil phase dispersed into emulsion droplets 2

5 Summary of lipid digestion & absorption TG MG FA MG FA (>10C) FA (<12C) chylomicron TG BILE SALTS chylomicron mixed micelle albumin BILE SALTS FA lipase- colipase apolipoproteins phospholipids emulsion droplet adapted from Devlin, 5th ed. pp BILE SALTS oil drop 18 4ATPs/TG enterocyte

6 Micelles important type of emulsion droplet important type of emulsion droplet essential component: amphiphilic molecules essential component: amphiphilic molecules two molecules thick (bilayer) two molecules thick (bilayer) other dimensions can vary widely in numbers of molecules other dimensions can vary widely in numbers of molecules polar nonpolar examples: examples: monomer unit: soluble monomers in rapid equilibrium with units in micelles soluble monomers in rapid equilibrium with units in micelles simple micelle: contains only one substance simple micelle: contains only one substance mixed micelle: more than one substance mixed micelle: more than one substance 3

7 key amphiphilic components of intestinal mixed micelles key amphiphilic components of intestinal mixed micelles structure: a bile acid (a 24-C steroid) linked (amide) to an amino acid structure: a bile acid (a 24-C steroid) linked (amide) to an amino acid aka conjugated bile acids aka conjugated bile acids most common bile salt in humans: glycocholate (cholate + glycine) most common bile salt in humans: glycocholate (cholate + glycine) other bile salts other bile salts taurocholate glycine replaced by taurine: H 2 NCH 2 CH 2 SO 3 – taurocholate glycine replaced by taurine: H 2 NCH 2 CH 2 SO 3 – glycochendeoxycholate differs from glycocholate by having no OH group on C12 glycochendeoxycholate differs from glycocholate by having no OH group on C12 Bile salts 4

8 Glycocholate structure polar functional groups grouped on 1 side, forming a polar face polar functional groups grouped on 1 side, forming a polar face 4-ring part is rigid, directing 3 OH's to point same way 4-ring part is rigid, directing 3 OH's to point same way side chain is flexible, allowing amide & COO – adjustment side chain is flexible, allowing amide & COO – adjustment away from the polar face are hydrocarbon atoms, forming nonpolar faces away from the polar face are hydrocarbon atoms, forming nonpolar faces – 5

9 Bile salt function stabilize mixed micelles stabilize mixed micelles bile salts amphiphilic structure suited for interfacing lipid surfaces & H 2 O bile salts amphiphilic structure suited for interfacing lipid surfaces & H 2 O form amphiphilic rim on bilayer sheets & disc-shaped micelles so that exposed nonpolar surfaces are form amphiphilic rim on bilayer sheets & disc-shaped micelles so that exposed nonpolar surfaces are shielded from H 2 O (covered up) shielded from H 2 O (covered up) unable to aggregate unable to aggregate N P N N P P N P N N P N N P N N P N N P P N P P N P P bilayer fragment with exposed nonpolar (N) surface bound bile salts interface with nonpolar surface & H 2 O 6

10 Bile salts: synthesis, secretion synthesized in the liver cholesterol synthesized in the liver cholesterol bile acid bile acyl-CoA + amino acid bile salt secreted as a component of bile secreted as a component of bile bile secretion stimulated by bile secretion stimulated by secretin (target: liver) secretin (target: liver) CCK (target: liver & gall bladder) CCK (target: liver & gall bladder) absorbed bile salts absorbed bile salts cylindrical micelle bile salt bile salt chol- esterol fatty acid monoglyceride phos- pholipid nonpolar surfaces polar face OH groups amide group carboxyl group mixed micelle cross-section Adapted from Physiology (Berne & Levy), Fig

11 Enterohepatic circulation (bile salt recycling) bile salts absorbed toward end of ileum bile salts absorbed toward end of ileum absorption by Na + – driven cotransport absorption by Na + – driven cotransport Na + –bile salt symport Na + –bile salt symport carried in portal blood bound to albumin carried in portal blood bound to albumin added to bile again by liver & secreted again added to bile again by liver & secreted again typically make 3-4 roundtrips during average meal typically make 3-4 roundtrips during average meal cholesterolbile salts Sherwood, Fig

12 Digestion of lipids: hydrolysis triglycerides (TG) triglycerides (TG) TG + H 2 O diglyceride + fatty acid (FA) diglyceride + H 2 O monoglyceride (MG) + FA Sum: cholesterol esters & phospholipids* (PL) esterase phospholipases cholesterol esters & phospholipids* (PL) esterase phospholipases FA + cholesterol (chol) FA + lysoPL FA + cholesterol (chol) FA + lysoPL in all cases, products are more polar than reactants in all cases, products are more polar than reactants reactions generate surfactants reactions generate surfactants + 2 H + 9 * biliary & dietary

13 Digestion of fats: lipase & colipase lipase: a globular protein unable to penetrate surface of lipid particles (can only reach surface molecules) lipase: a globular protein unable to penetrate surface of lipid particles (can only reach surface molecules) salivary lipase: active at low pH salivary lipase: active at low pH pancreatic lipase: active at pH >7 pancreatic lipase: active at pH >7 hydrolyzes >80% of dietary fat hydrolyzes >80% of dietary fat colipase colipase required cofactor anchors lipase to lipid particles required cofactor anchors lipase to lipid particles nonpolar domain (tail) binds to lipid particle nonpolar domain (tail) binds to lipid particle polar domain binds & activates lipase polar domain binds & activates lipase TG particle colipase lipase 10

14 Particle transitions: formation of mixed micelles initial hydrolysis & dispersion initial hydrolysis & dispersion oil phase emulsion droplets oil phase emulsion droplets average particle size: 1000 μm 10 μm average particle size: 1000 μm 10 μm dispersion to emulsion droplets due to hydrolysis products (e.g., MG & FA) being amphiphiles dispersion to emulsion droplets due to hydrolysis products (e.g., MG & FA) being amphiphiles bile salts & phospholipids also contribute to dispersing of oil drops bile salts & phospholipids also contribute to dispersing of oil drops additional hydrolysis & mixed micelle formation additional hydrolysis & mixed micelle formation emulsion droplets mixed micelles emulsion droplets mixed micelles as [FA] & [MG], they leave droplets & combine with bile salts to form mixed micelles as [FA] & [MG], they leave droplets & combine with bile salts to form mixed micelles average particle size reduced from 10 μm to 10 –2 μm average particle size reduced from 10 μm to 10 –2 μm 11

15 Lipid particle summary particle size range,surfacemolecular components type μ m area, cm 2 /g surfaceinside* oil drop 10 2 – – 100TG TG emulsion 1 – – 10 4 FA, MG, PL, TG droplet bile salts, TG mixed 10 – 3 – 10 – – 10 7 bile salts, FA, – micelle MG, PL chylo- 10 – 1 – – 10 5 apolipo- TG micron proteins, PL * all contain chol, chol esters & fat-soluble vitamins relative diameters of small circle & large (part) circle is

16 Lipid particles TG, DG MG, FA, etc. MG, FA, etc. TG emulsion droplet mixed micelle

17 Absorption from lumen brush border membrane microvillus diffusion of micelles through unstirred layer well-mixed luminal contents monoglycerides lysophos- pholipids chol fatty acids unstirred layer cytosol u movement of lipid digestion products (FA, MG, etc) across mucosal plasma membrane by simple diffusion of monomers u absorption also occurs via fatty acid transfer protein (FATP) u microvilli provide very large absorbing surface, but convolutions & glycocalyx produce unstirred layer Adapted from Fig (B & L) FATP 13

18 Absorption: role of micelles unstirred layer unstirred layer μm thick μm thick prevents peristaltic mixing from moving luminal contents close to cell surface prevents peristaltic mixing from moving luminal contents close to cell surface crossed by micelle diffusion crossed by micelle diffusion because of very low solubility of lipid molecules & very large distance, absorption would be very slow without micelles mixed micelles act as: mixed micelles act as: carriers of lipid monomers (FA, MG, chol, vit. A, D, E, K) carriers of lipid monomers (FA, MG, chol, vit. A, D, E, K) reservoirs: as monomers absorbed, they are rapidly replaced by dissociation from micelles reservoirs: as monomers absorbed, they are rapidly replaced by dissociation from micelles 14

19 After absorption FAs (>10Cs) & MGs converted into TGs FAs (>10Cs) & MGs converted into TGs after diffusion into smooth ER, FAs activated, forming acyl-CoAs ( 2 ATPs used/FA ): after diffusion into smooth ER, FAs activated, forming acyl-CoAs ( 2 ATPs used/FA ): FA + CoA acyl-CoA FA + CoA acyl-CoA from these, TGs synthesized: from these, TGs synthesized: 2 acyl-CoA + MG TG PL & chol esters (cholE) also resynthesized PL & chol esters (cholE) also resynthesized products packaged into chylomicrons products packaged into chylomicrons Adapted from Fig (B & L) MG+ 2FA lysoPL +FA chol +FA TG PLcholE chylomicron lipopro- tein coat exocytosis MG+FA lysoPL chol smooth ER lacteal 15 for WebPage

20 Packaging for transport chylomicrons chylomicrons particles for transport of lipids to liver & adipocytes particles for transport of lipids to liver & adipocytes size: 0.1–1 µm size: 0.1–1 µm average composition: average composition: TG (84%) chol (2%) cholE (4%) PL (8%) apolipoproteins (2%) apolipo- proteins cholE, TG chol PL Lehninger et al., 2nd ed., Fig PL Lehninger et al., 3rd ed., Fig

21 Export of chylomicrons exocytosis exocytosis chylomicrons enclosed in secretory vesicles in Golgi complex chylomicrons enclosed in secretory vesicles in Golgi complex vesicles diffuse to basolateral membrane vesicles diffuse to basolateral membrane via fusion, chylomicrons released into interstitial space via fusion, chylomicrons released into interstitial space chylomicrons enter chylomicrons enter lymphatic system (lacteals) by diffusion lymphatic system (lacteals) by diffusion blood at thoracic duct from lymphatics blood at thoracic duct from lymphatics FAs with <12 Cs FAs with <12 Cs diffuse through cell & basolateral membrane, into blood diffuse through cell & basolateral membrane, into blood transported in blood bound to albumin transported in blood bound to albumin vesicle membrane lacteal 17

22 Summary of lipid digestion & absorption TG MG FA MG FA (>10C) FA (<12C) chylomicron TG BILE SALTS chylomicron mixed micelle albumin BILE SALTS FA lipase- colipase apolipoproteins phospholipids emulsion droplet adapted from Devlin, 5th ed. pp BILE SALTS oil drop 18 4ATPs/TG enterocyte

23 Next: 3. Distribution of absorbed nutrients


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