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• 1 NBA1 (molecular aspects of) protein digestion and absorption

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• Which proteins can be found in our GI tract?

  Dietary proteins 
  
  

  • different sources (meat, dairy, legumes, nuts etc)

  
  Endogenous proteins 
  

  • salivary and gastric secretions 
  • pancreatic and bile secretions 
  • small intestinal secretions 
  • sloughed epithelial cells 
  • mucus 
  • microbial protein 

  
  

• Which enzymes are there for the protein digestion

  Endopeptidases - internal bonds 
  Exopeptidases - amino acid from the carboxy- or amino- terminus 
  
  

  • Pepsin - endo
  • Trypsin - endo 
  • Chymotrypsin - endo 
  • Elastase - endo
  • Carboxypeptidase A - exo
  • carboxypeptidase B - exo
  • Aminopeptidases - exo

• But .... Enzyme digestion is not exactly straight forward, why?

  • Specificity for a cleavage site 
    
  • but not all cleavage sites on a protein are always utilised by an enzyme 
  • peptide composition from hydrolysis is difficult to predict, it depends on selectivity of enzyme towards cleavage site 

  
  
  spontaneous non-enzymatic breakdown 
  

  • whey protein hydrolysate: 13/77 identified peptides from a-specific cleavage, even in mild conditions 

• What is the rol of PEPT1 in the protein absorption?

  Peptide transport protein PEPT1
  
  

  • Transport/absorption of di- & tri-peptides
  • Very broad substrate specificity
  • >400 dipeptides and >8000 tripeptides
  • Low affinity
  • Secondary active transport (no direct ATP)

  
  
  NHE3 is important for the proton gradient --> Na+ wil go into the cell and H+ will go out of the cell
  

• What is the role of the AA transport system for protein absorption?

  • Many different transporters
    
  • Transporters have:
  • stereospecificity --> L-amino acids
  • substrate specificity --> multiple amino acids
  • overlap in specificity --> multiple transporters per AA
  • Mechanism:
  • facilitated diffusion
  • secondary active transport

  
  

• Which inherited diseases influence the absorption?

  Hartnup disorder:
  

  • Defective intestinal transport: B0AT1 (neutral AA)
  • Effect: poor nutrition results in pellagra-like skin changes, cerebellar ataxia, and psychiatric abnormalities
  • Treatment: sometimes only a high protein diet!

  
  Cystinuria:
  

  • Defective intestinal transport: rBAT/b0,+AT (cationic AA)
  • Effect: kidney stones made of Sistine (transporter also absent in kidneys for reabsorption)
  • Treatment: multiple options to prevent kidney stones

• Which parts of the intestine are involved in the absorption (along the intestine)

  Duodenum  (4)
  Jejunum  (1)
  Ileum (2) 
  Proximal colon (5)
  Distal colon  (3)

• What happens in the after protein absorption - in enterocytes?

  Di & tripeptides --> AA
  

  • by intracellular peptidases

  
  Free amino acids (AA)
  

  • metabolism (in enterocyte)
  • glutamine, glutamate and aspartate oxidised
  • protein synthesis
  • transport over basolateral membrane --> blood

  
  

• What happens after protein absorption in the circulation?

  • Release of dietary protein-derived amino acids in circulation
    
  • From intestinal capillaries to peripheral circulation
  • via portaal vein to liver
  • first pass metabolism - splanchnic amino acid extraction ± gut + liver

  
  

  • Fast vs. Slow protein concept
  • whey vs casein
  • whey has a high increase and after that a decrease
  • casein stays 'stable' 
  • whey is better than casein

  • influence anabolic effect

• What are the key points in the fast vs slow protein concept

  • Speed of protein digestion depends not only on proteins sources, but also on food matrix, texture, technological processes and associated calories
    
  • Fast digestive proteins are efficient for improving muscle mass and muscle function in older individuals through the postprandial changes in amino acid availability
  • The anabolic effect of fast digestive proteins, especially whey protein, is amplified by physical exercise