Digestion and absorption in GI tract Flashcards
Digestive functions
Localised to different areas of the gut where:
-optimal pH of enzymes differ
-some enzymes may be secreted as inactive precursors, and need enzymatic activation
-some enzymes exist as membrane bound forms
-Objective is to break macromolecules down into monomer or dimer units for absorption
Absorption functions
-Mainly in small intestine, but also water in colon
-Requiring a variety of transport mechanisms specific for particular molecules
-If transport is against a gradient, energy must be used (primary or secondary active transport)
Small intestine villi structure
Membrane pumps, enzymes and transporters in small intestine enterocytes
Enzymes - required for digestion of macromolecules
Transporters - required for absorption of many solutes (products of digestion)
Na pump:
-Maintains Na gradient (low Na inside cell) which is required by many transporters
-Creates osmotic gradient in intracellular space, which drives water absorption from lumen
Protein digestion step 1 (pepsin and HCL)
-Starts with pepsin and HCl in the stomach
Protein digestion step 2 (chyme)
Chyme has a LOW pH and contains:
-Solubilised, slightly digested carbohydrates
-Solubilised, partly digested proteins
-Slightly digested fats
-Intrinsic factor which enables Vit B12 to be absorbed in the small intestine
For further digestion to take place:
-other enzymes are supplied (from pancreas and made by enterocytes)
-pH has to be neutralised
-bile salts needed for fat digestion
Protein digestion step 3 (duodenum)
In duodenum:
-Enterokinase on brush border of duodenal enterocytes activates pancreatic trypsinogen
-This activates proteolytic enzymes of the pancreas
Protein digestion step 4 (duodenum)
-Pancreatic trypsin, elastase & chymotrypsin (endo-peptidases) cleave peptide bonds in protein interior, producing short peptides
-Pancreatic carboxypeptidases (exopeptidase) remove amino acids from the carboxyl ends
-Aminopeptidases (exo-peptidase) on brush border of enterocytes remove amino acids from the amino terminal of peptides
Amino acid and peptide absorption
-Amino acids absorbed via Na+-linked lumenal transporters, then exit on basolateral side
-Di- and tri-peptides absorbed via H+-linked lumenal transporters, then hydrolysed to amino acids before exiting on basolateral side
Why is infant small intestine wall permeable to peptides?
-Allows for absorption of growth factors and antibodies from colostrum (first milk)
Types of carbohydrate in food
Carbohydrate digestion summary
1) Salivary amylase
-optimum pH is 6.8, so some hydrolysis in the mouth
-swallowed bolus then enters acidic stomach
2) Pancreatic amylase
-optimum pH is 7.1
3) Small intestine membrane-bound disaccharidases:
-optimum pH values between 6 and 7
Carbohydrate digestion (molecular level)
Pancreatic amylase:
-Cleaves straight chains but cannot cleave bonds at branch points
-Produces short oligosaccharides, maltose (disaccharide) and maltriose (trisaccharide)
-Further digestion of these and other disaccharides (lactose, sucrose) to monosaccharides by brush border enzymes
Carbohydrate absorption
Apical/lumenal side:
-SGLT (Na-linked transporter) for glucose & galactose, secondary active transport
-Fructose via GLUT5, facilitated diffusion
Basolateral side:
-GLUT2 transport for all three hexoses, facilitated diffusion
-Na pump maintains Na gradient
Fat digestion summary
Enzymes: mainly pancreatic lipase but some gastric lipase
Other requirements:
-Colipase
-Bile salts
-Right pH
=>for digestion in duodenal lumen
-Beta lipoprotein
=>Inside enterocyte, to ‘package’ lipid for export as chylomicrons
4 steps in fat digestion
-Emulsification of fat in lumen (requires bile salts)
-Action of lipase to convert TGs to MGs and FAs
-Formation of micelles (made of MGs, FAs, bile salts, etc)
-Diffusion of micelles to epithelial cell brush border
What is the action of lipase?
-Breaks down triglycerides into 2 fatty acids + monoglyceride
4 steps in fat absorption
-Trans-membrane transport of the free FAs and MGs (by diffusion through the lipid core)
-Intracellular resynthesis of triglyceride (in the SER)
-Incorporation of the TG into chylomicrons, together with beta-lipoprotein, cholesterol, etc
-Efflux of the chylomicrons on the basolateral side of the cell, into nearby lacteals
Enterohepatic recirculation of bile salts
-95% bile salts reabsorbed, mainly in terminal ileum
-Transported back to liver via portal vein, and re-extracted by hepatocytes to be re-exported in bile juice
-Can be turned over 3-4 times during digestion of a single large meal
-Overall loss of 5-10% per day in faeces compensated by de novo synthesis in liver
Water absorption in colon
-Net water absorption (following Na+ down osmotic gradient)
-Water and Na reabsorption stimulated by aldosterone
-Resident microflora are prevented from crossing epithelial barrier, but they help to produce vit. K and folic acid which are absorbed here
Other absorptive functions of GI tract
Minerals
-Specific mechanisms for absorption of mineral ions such as Ca2+, Fe2+ etc
Vitamins
-Specific mechanisms for B & C vitamins
-Fat-soluble vitamins generally absorbed with lipids, in SI
Drugs
-Absorbed best when non-ionised, both in the SI (right pH) and colon
-Limited absorption of a few drugs (e.g. aspirin) across gastric mucosa
Absorption of Vitamin B12
-Haptocorrin protects B12 from acidic stomach
-IF produced in stomach and takes over from Haptocorrin, protecting it and allowing it to be absorbed in intestines
-Vit B12/IF complex binds to cubam receptor, taken up in distal ileum
Absorption of calcium
Calcium is an active signalling molecule so need to stop it acting in the enterocyte - calbindin
-Paracellular route (Claudin 2 +12)
-Enters through TRPV6/Cav1.3, binds to calbindin, exits via Ca ATPase pump and Na/Ca exchanger
Absorption of iron
-Cannot absorb Fe3+ only Fe2+
-Dyctb converts 3+ to 2+, 2+ can be transported
-Fe2+ enters through DMT1
-Heme is converted to Fe2+ by Hemeoxygenase (HO-1)
-Fe2+ can be stored in cell as ferritin or transported into blood via ferroportin transporter
