W7 L16: GI Tract pt5

Digestion & Absorption Protein & Lipids

Amino acids are building blocks of protein

Proteolytic enzymes

  • Exopeptidase enzymes
    • Carboxy- or amino-peptidases
    • liberate free individual amino acids
  • Endopeptidases
    • liberate smaller peptide chains

 

Digestion of proteins

  • Mechanical disruption by chewing and gastric motility
  • Protein denaturation by HCl
  • Combined effect of chemical and enzymatic digestion

Stomach

  • Enzymatic digestion of proteins begins
  • Pepsin
    • secreted by chief cells
    • most effective in v. acidic environment of stomach (pH2)
    • becomes inactive at higher pH
  • Cleaves certain peptide bonds b/w amino acids
    • smaller peptide fragments (polypeptides)
    • breaks peptide bonds adjacent to phe, tyr, aps, glu, leu, met

What prevents pepsin from digesting the protein in stomach cells?

  1. Pepsin is secreted in an inactive form → pepsinogen
    • pepsinogen is converted into active pepsin when it comes in contact w/
      • HCl secreted by parietal cells
      • active pepsin mols.
  2. Stomach epithelial cells protected from gastric juices
    • layer 1-3 mm thick alkaline mucus
    • secreted by surface mucous cells & mucous neck cells

Small intestine

  • Pancreatic juice

    • trypsin
    • chymotrypsin
    • carboxypeptidase
    • elastase

  • Produces in an inactive form to protect pancreas

  • Trypsin secreted in inactive form → trypsinogen

  • Pancreatic acinar cells secrete trypsin inhibitor - to protect itself

    • blocks enzyme of any trypsin formed accidentally in pancreas or in pancreatic juice

  • Trypsinogen reaches lumen of SI

    • activating brush-border enzyme → enterokinase
    • splits off part of trypsinogen → trypsin

  • Trypsin acts on other inactive precursors

    • chymotrypsinogen → chymotrypsin
    • procarboxypeptidase → carboxypeptidase
    • proelastase → elastase

Endopeptidases

  • trypsinogen
  • chymotrypsinogen
  • proelastase

Exopeptidases

  • procarboxypeptidase A
  • procarboxypeptidase B

 

Protein digestion completion
  • 2 peptidases in the bush border
  • Aminopeptidase
    • cleaves off amino acid at amino end of peptide
  • Dipeptidase
    • splits dipeptides (2 amino acids joined by a peptide) into single amino acids

 

Absorption of proteins
  • most proteins absorbed as amino acids via active transport processes
    • duodenum & jejunum
  • 50% of absorbed AA are present in food
  • 50% from the body
    • protein in digestive juices
    • dead cells sloughed off mucosal surface
  • 95% - 98% of protein present in SI is digested & absorbed
  1. Na+ dependant AA transport - individual AA
  2. H+ co-transport w/ small peptides
    • dipeptides & tripeptides
    • hydrolysed to single AA inside absorptive cells
    • AA move out of absorptive cells via diffusion
  3. Larger peptides moved by transcytosis

 

Absorption R of proteins

  • AA transported in blood to liver (hepatic portal system)
  • Hepatocytes deaminate (remove NH2) AA
  • AA
    • ATP production
    • converted to carbohydrates of fats
  • Toxic ammonia (NH3) converted into much less toxic urea (excreted in urine)
  • Hepatocytes synthesised most plasma proteins
    • α & β globulins, albumin, prothrombin & fibrinogen

Summary of proteins:

  • Protein digestion begins in stomach
    • HCl denatures proteins
    • pepsin begins enzymatic digestion
  • Pancreatic juice secreted into SI
    • pro-enzymes are activated
    • peptidases in brush border
  • AA & peptides are absorbed by 3 mech. of active transport
  • AA are processed by the liver

Lipids

What fat enters the GI tract

Triglycerides

  • Most abundant lipids in the diet
  • Molecule of glycerol bonded to 3 fatty acid mols.

Dietary:

  • 100 g/day (RNI 70 g/day)
  • 90 % triacylglycerol
  • 5 % phospholipids
  • 0.5 % cholesterol ester

Endogenous (make):

  • bile 10 – 15 g
  • phospholipid
  • 1 – 2 g cholesterol
  • ester 6 g
  • intestinal cells
  • 10 g dead bacteria

Mouth

  • Lingual glands in lamina propria of the tongue
  • Secrete mucus & lingual lipase
  • Acts on ~30% of dietary triglycerides (fats & oils)
  • Converts them to simpler FAs & diglycerides

Stomach

  • Chief cells
  • Gastric lipase
    • operates best at pH 5-6
  • Splits triglycerides into FA & monoglycerides
    • monoglycerides → glycerol mol. + 1 FA mol.

Small intestine

  • Most lipid digestion occurs here
  • Pancreatic juice - pancreatic lipase
  • Bile salts - emulsification
  • Triglycerides broken down into FAs & monoglycerides
  • Short chain FAs
    • fewer than 10-12 carbons
    • hydrophobic - more water-soluble than longer FAs
  • Long chain FAs
    • Large short-chain FAs (w/ more than 10-12 carbon atoms)
    • Hydrophobic - not water-sol.

Pancreatic lipase is made up of 3 separate enzymes

 

Action of pancreatic enzyme

  • Triacylglycerol hydrolase
  • Specific for first and third ester bonds
  • Maximal enzymatic efficiency requires:
    • colipase (stabilises active catalytic site), prevents inactivation by bile salts
    • alkaline pH
    • bile salts for emulsification

 

Bile salts
  • Na+ salts & K+ salts of bile acids
  • Amphipathic
    • hydrophobic (nonpolar) region
    • hydrophilic (polar) region
  • Emulsification
    • hydrophobic region interacts w/ large lipid globule
    • hydrophilic region interact w/ watery intestinal chyme
    • large lipid globule is broken down into several small lipid globules (1μm in diameter)
    • Breakdown of large lipid globules into suspension of small lipid globules
    • Crucial in ↑ SA for lipase action

 

Micelles

  • ↑ solubility (2-10nm diameter)
  • 20-50 bile salts mol.
  • Hydrophobic regions of bile salts interact w/ FAs & monoglycerides
  • Hydrophilic regions of bile salts interact w/ watery intestinal chyme
Lipid digestion

  • Emulsification by bile salts

  • Formation of mixed micelles

  • Micelle breaks down close to luminal surface

    • low pH of acid microclimate zone

  • Fatty acids are released to be absorbed by epithelial cells

  • All dietary lipids are absorbed via simple diffusion

  • Adults absorb about 95% of lipids present in SI

  • Small short-chain FAs

    • dissolved in watery intestinal chyme
    • pass through absorptive cells via simple diffusion
    • into blood capillary of a villus

  • Micelles move to bush border of absorptive cells

  • Large short chain and long chain FAs, & monoglycerides diffuse out of micelles into absorptive cells

  • Micelles remain in chyme

  • Micelles continually repeat ferrying function

  • Move back to interior of small intestinal lumen

  • Pick up more of large short chain and long chain FAs, & monoglycerides

  • Micelles also solubilise other large hydrophobic molecules en

    • fat-sol. vits (A, D, E & k)
    • cholesterol

  • Inside absorptive cells

    • long chain FAs & monoglycerides are recombined to form triglycerides
    • aggregate into globules along w/ phospholipids & cholesterol & cholesterol and become coated w/ proteins (chylomicrons)

Chylomicrons

  • large spherical masses
  • ~80nm in diameter
  • Leave absorptive cells via exocytosis
    • cannot enter blood capillaries
  • Absorbed into lymphatic system and into lacteal
  • Too large to enter capillary directly
  • Transported by lymphatic vessels to thoratic duct

   

  Intestinal villus

  • Enter the blood at the junction of the left internal jugular & left subclavian veins
  • Hydrophilic protein coat
    • keeps chylomicrons suspended in blood
    • prevents them from sticking to each other

Lipid absorption

  • Within 10 mins ~50% chylomicrons have been removed from blood
  • Enzyme attached to apical surface capillary endothelial cells
    • Lipoprotein lipase → breaks down triglycerides in chylomicrons & other lipoproteins into FAs & glycerol
    • FAs diffuse into hepatocytes & adipose cells & combine w/ glycerol during re-synthesis of triglycerides
  • 2-3 hours after a meal, few chylomicrons remain in blood

Enterohepatic circulation

  • Most bile salts are reabsorbed by active transport in ileum
  • Returned by blood to liver through hepatic portal system
  • Re-secreted into bile
  • Insufficient bile salts
    • obstruction of bile ducts
    • removal of gallbladder
    • diminished lipid absorption
    • loss of up to 40% of dietary lipids in faeces

Lipid metabolism in liver

  • Hepatocytes store some triglycerides
  • Break down FAs to generate ATP
  • Synthesise lipoproteins
    • transport FAs, triglycerides & cholesterol to & from body cells
  • Synthesise cholesterol
  • Use cholesterol to make bile salts