Lecture PSL302: 67, by French!
Fri. Apr. 1, 2011
Digestion & Absorption
Outline - Review composition of carbohydrates, protein and fat - How and where are carbohydrates/proteins/fats digested and absorbed? - How are vitamins, electrolytes & water absorbed? Textbook reading: 73-708, 715-718 (5E), 693-699, 706-710 (4E) Review composition of carbohydrates, protein and fat Recall: Fxns of digestive system! Recall: Functions of digestive system ! !
Recall: GI secretion and absorption Recall: GI secretion & absorption
carbohydrates, fat, protein, ,p , water, electrolytes vitamins
CIRCULATION
monosaccharides fatty acids monoglycerides cholesterol amino acids water, vitamins, electrolytes waste
CONTROL
- Digestion (breakdown of nutrients) must occur before absorption
Figure 21.3
Figure 21.2
Types of Transport - Transcellular: mvt thru cell; usually requires pump or channel, except lipid solubles - Paracellular: pass btwn cells - Transcytosis: mvt of larger molecules thru cells via vesicle transport Carbohydrates
Types of transport
transcellular transcell lar
paracellular transcytosis
Carbohydrates
Modified Figure 21-14
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PSL302: Lecture 67, by French!
Fri. Apr. 1, 2011
Proteins
Fat
Overview of digestion and absorption
Figure 21-16a
Figure 21-18
Overview of digestion and absorption
Mouth Stomach
Small intestine
Epithelial cell
Blood or lymph
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PSL302: Lecture 67, by French!
Fri. Apr. 1, 2011
How and where are carbohydrates/proteins/fats digested and absorbed?
Carbohydrates -- mouth and stomach
Carbohydrates: mouth & stomach - Mouth: salivary amylase = 5% of starch is broken down to maltose (disaccharides) - Also broken down to maltotriose & limit dextrin (branched glucose chain) - Stomach: digestion continues until amylase is denatured by low pH - 35% of starch broken down to maltose ! : small intestine - Pancreatic amylase more potent than salivary amylase - Principle place of digestion in duodenum - Small carbohydrates still must be broken into monosaccharides - Brush border enzymes: embedded in plasma membranes of intestinal villi epithelial cells - Convert small carbohydrates to monosaccharides - Enzyme specificity: i.e. maltase-glucoamylase cleaves maltose & maltotriose - Some ppl are lactose-intolerant: insufficient lactase lactose remains in lumen of gut = diarrhea b/c lactose is osmotically active - Monosaccharide transporters: i.e. GLUT-5, Na+/glucose-linked transporter (SGLT) - Uniporter: transport only monosaccharides ! : Absorption
salivary amylase Maltotriose
Maltose
Starch
Limit dextrin
Mouth: 5% of starch is broken down to maltose Stomach: Digestion continues until amylase exposed to g y p low pH (35% of starch broken down to maltose)
Carbohydrates -- small intestine
pancreatic amylase Maltotriose
Maltose
Starch
Limit dextrin
Brush border enzymes convert small pancreatic amylase is monosacchrides carbohydrates tomore potent than salivary amylase
Sucrose Lactose
MaltaseDextrinase Sucrase glucoamylase
Lactase
GLUT-5
Sodium glucose-linked transporter
Carbohydrates -- absorption
- At apical side, transport in of: - Glucose & galactose via SGLT - Fructose via GLUT-5 uniporter - At basolateral side, transport out of: - All monosaccharides out by GLUT-2 - Use glucose gradient to move: - SGLT: 2 active transport - GLUT-2 uniporter: passive diffusion Protein digestion begins in the stomach - Acid denatures proteins - Also activates pepsinogen by cleaving it = pepsin - Pepsinogen released from chief cells: endopeptidase - Activated by itself (pepsin) or by acid - Pepsin cleaves proteins at aromatic aas such as Phe, Trp & Tyr
Protein digestion begins in the stomach
Figure 21-15
acid
Protein
Peptides and amino acids
Pepsinogen released from chief cells Pepsin cleaves proteins at aromatic amino acids such as p e y a a e, tryptophan and tyrosine phenylalanine, t yptop a a d ty os e
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PSL302: Lecture 67, by French!
Fri. Apr. 1, 2011
Protein digestion -- small intestine
! : small intestine - Pancreatic enzymes activated by enterokinase/ enteropeptidase (brush border enzymes) - When inactive, called zymogens - Cleaves trypsinogen trypsin - Trypsin activates trypsinogen, chymotrypsinogen, & procarboxypeptidase - Break down proteins even further Details: activation of pancreatic enzymes (1) Pancreatic secretions inactive zymogens - Proteases: chymotrypsinogen, procarboxypeptidase - Trypsinogen: activating factor (2) Trypsinogen activated by enteropeptidase/ enterokinase in brush border = trypsin - Trypsin activates proteases (3) Activated: chymotrypsin, carboxypeptidase - Trypsin & chymotrypsin are endopeptidases - Carboxypeptidase (exopeptidase) removes single aas from COOH end of protein
Enterokinase (Enteropeptidase)
Details: activation of pancreatic enzymes
Protein digestion: brush border enzymes Protein digestion: brush border enzymes - Breakdown of di- & tripeptides into aas Trypsin and chymotrypsin are endopeptidases - Aminopeptidase: remove aas from NH3 end of protein removes single amino acids from the Carboxypeptidase - Dipeptidase: cleave dipeptides into single aas of the protein COOH end Figure 21-29 - Not all peptides broken into aas
Proteins: absorption
Proteins: absorption
Aminopeptidase
Dipeptidase
-PepT-1 co-transporter: uses H+Figure from Interactive Physiology, Pearson to bring di& tripeptides into cell -Na+/amino acid cotransporter -Transcytosis: carried peptides intact w/o breakdown by peptidases inside cell
PepT 1
Figure 21-17
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PSL302: Lecture 67, by French!
Fri. Apr. 1, 2011
Fat digestion: mouth and stomach
Fat digestion: mouth & stomach
triglycerides
linguinal lipase
gastric lipase
monoglycerides free fatty acids
Bile salts emulsify fat in small intestine
Bile - Minimal digestion of triglycerides monoglycerides + free salts are derived from fatty acids - cholesterol Mouth: lingual lipase minimal digestion Large fat droplets - stomach forms smaller lipase agitation inStomach: gastric fat droplets - Agitation = smaller hydrophobic fat droplets - So rely on digestion in small intestine
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Bile salts
Bile salts emulsify fat in small intestine - Bile salts are derived from cholesterol emulsion - Hydrophobic portions coat fat Bile salts help to form micelles - Hydrophilic portions allow dissolution bile salts and thephospholipase phospholipid lecithin from liver emulsify fat Pancreatic - Bile salts & phospholipid lecithin from liver emulsify fatincreases the surface area for further digestion - Emulsion: lg fat droplets smaller fat droplets p pancreatic lipase p - Not digesting fat BUT SA for further digestion
colipase bile salts
- Digestion by pancreatic lipase & colipase (cofactor) + bile salts help to form micelles - Tiny particles of fat coated w/ bile salts - Contain mono- & diglycerides, phospholipids, free fatty acids (FFA), cholesterol
micelles
Figure 21-19
Fat: absorption - In small intestine: Micelles contact the brush border - Transport into cell: Monoglycerides & FFA diffuse into the cell - Cholesterol enters via an energy-dependent transporter (e.g. NPC1L1) Fat -- absorption - Inside cell at smooth ER: Re-esterified (re-synthesized) to triglycerides Fat absorption cont'd
Cholesterol Monoglycerides diffusion Free fatty acids
micelles contact the brush border monoglycerides and free fatty acids diffuse into the cell reesterify to triglycerides in the smooth ER cholesterol enters via an energy dependent transporter (e.g. NPC1L1)
Smooth ER
At Golgi: = chylomicron - Particles of fat & triglycerides w/ protein coat - Packaged into vesicles & secreted from the cell via exyocytosis - Absorbed by lacteal into the lymphatic system - Don't enter bloodstream (can't pass thru endothelial cells)
triglycerides to Golgi assemble with proteins to Smooth ER form chylomicrons chylomicrons packaged into Golgi vesicles and secreted from the cell via exocytosis absorbed by the triglycerides assemble w/ proteins lymphatic system
Golgi chylomicron
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PSL302: Lecture 67, by French!
Fri. Apr. 1, 2011
Summary of fat digestion in small intestine
= emulsion of fat = digestion = form micelles = absorbed into epithelial cells by diffusion
= re-synthesis of triglycerides at smooth ER = package into chylomicrons at Golgi apparatus
Chylomicron
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Chylomicrons travel via lymphatics to the thoracic duct, which drains into the blood at the left subclavian vein.
= absorbed into lacteal lymphatic system drains into bloodstream taken up by liver & repackaged w/ glycoproteins (i.e. LDL, HDL) Chylomicrons
phospholipid cholesterol apoprotein apoprotein cholesterol esters triglycerides
Figure 21-20
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Chylomicrons - Inside: cholesterol esters & triglycerides = hydrophobic - Outside: protein coat (apoproteins & phospholipids) triglycerides in chylomicrons FFA and glycerol by - In capillaries: triglycerides FFA & glycerol by lipoprotein lipase lipoprotein lipase in capillaries used for energy or stored as triglycerides gy gy - Used for energy or stored as triglycerides chylomicron remnants taken up by liver - At liver: chylomicron remnants taken up & repackaged - Can also go to other parts of body How are vitamins, electrolytes & water absorbed? Vitamins - Fat soluble vitamins (vit A, D, E, K): absorbed w/ fat - Water soluble vitamins (vit C and most B): absorbed via transporter - Vitamin B12: made by gut bacteria, but also in seafood, meat & milk - Binds to intrinsic factor (synthesized by parietal cells in stomach) - Absorbed in ileum via transporter
Calcium and iron absorption
Electrolytes: calcium - Enter: via Ca2+ channel in apical membrane (down conc gradient) - Inside cell: binds to calbindin protein - Calcitriol: Ca2+ absorption by calbindin synthesis; derived from vit D - Transported out: via Ca2+ ATPase
Calcium Ca2+ Ca2+ Ca2+ channel Ca2+ ATPase Iron Fe2+ H+ DMT 1 DMT-1 Fe2+ ferroportin (levels decreased by hepcidin h h idi hormone released by the6 of liver) Ca2+ Ca2+ calbindin (levels increased by calcitriol)
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Calcium and iron absorption
Calcium Ca2+ Ca2+ Ca2+ calbindin (levels increased by calcitriol) Fri. Apr. 1, 2011 Ca2+ ATPase
PSL302: Lecture 67, by French!
Ca2+ Ca2+ channel
Electrolytes: iron (Fe2+) - Enter: via divalent metal transporter (DMT-1): symporter uses H+ gradient - Transported out: via ferroportin - Influenced by hepcidin (released by liver) - hepcidin ferroportin absorption
Iron Fe2+ H+ DMT 1 DMT-1 Fe2+ ferroportin (levels decreased by hepcidin h h idi hormone released by the liver)
NaCl absorption
Electrolytes: NaCl absorption - Enter: via multiple pathways Water absorption - Na+ channels, Na+/Cl- symporter (balanced by HCO3-), Na +/H+ antiporter Water moves by: - Transported out: Na+/K+ ATPase Water absorption - Waver moves by: - Osmosis: transcellular or - Creation of osmotic gradients via solute transport: Co transport / e.g. Na+/glucose transport of solutes into intestinal epithelial cell 250 H20 transporter (approx. & molecules) transport of solutes out of the cell on the basolateral side - Co-transport: e.g. Na+/glucose transporter - Also ~250 H2O molecules co-transported = ~50% water (4L) absorbed per day Summary
Osmosis / aided by the transport of solutes into the intestinal epithelial cell and the transport of solutes out of the paracellular cell on the basolateral side transport
Figure 21-21
Loo DDF et al. (2002) J. Physiol. 542.1:53H60
Summary
Figure 21 22
Review: - Most digestion of disaccharides to monosaccharides occurs through the action of digestive enzymes located in the: brush border of the small intestine.
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