Nutrient Assimilation

Nutrient Assimilation

Nutrient Assimilation

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Assimilation = digestion + absorption

  • Digestion
    • physical reduction of food (chewing, grinding)
    • chemical reduction of complex nutrients into constituent monomers, dimers or trimers by enzymatic hydrolysis
    • luminal phase and membranous phase
  • Absorption
    • transport of products of digestion from gut lumen, across mucous membrane, into blood
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Carbohydrate Digestion

  • Complex sugars - polysaccharides (starch)
  • Simple sugars - mono and disaccharides
  • Common dietary sugars (disaccharides)
    • sucrose - glucose and fructose
    • lactose - glucose and galactose
    • maltose - glucose and glucose
  • Cellulose
    • plant material, indigestible, fibre - helps with propulsion through GI tract
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Glycosidic Bond Digestion

  • alpha-amylases cleave alpha-1,4-glycosidic linkages in polysaccharides (starch)
  • dextrinase cleaves 1,6-glycosidic bonds

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Carbohydrate Digestion

  • Salivary amylase
    • begins the 'luminal phase' digestion of starches action continues in stomach
  • Pancreatic amylase
    • continues 'luminal phase' digestion of starches in small intestine
    • structurally different from salivary amylase but identical catalytic action
  • Brush border enzymes
    • membranous phase of digestion
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Carbohydrate Digestion

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Absorption of Monosaccharides

  • Principal monosaccharide products of carbohydrate digestion are hexoses
  • Hexose absorption occurs by three mechanisms:
    • passive diffusion (slow and limited)
    • Na+/glucose symport
    • Na+-independent facilitative transpot

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Absorption of Monosaccharides

  • Na+/glucose symport mechanism
    • glucose and galactose are transported from the lumen into epithelial enterocytes by a Na+/glucose co-transporter SGLT-1 (sodium dependent glucose transporter)
  • Facilitated transport of hexoses
    • glucose transporter proteins expressed in all cell types
    • GLUT-1, GLUT-2 and GLUT-5 expressed in enterocytes
    • Fructose is absorbed from lumen by GLUT-5 on apical membrane
    • GLUT-2 on basal membrane transports hexoses from enterocyte cytosol to extracellular space
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Absorption of Monosaccharides

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Protein Digestion

  • 20 different amino acids may be joined by peptide linkaeges
  • Forms many thousands of known proteins and polypeptides

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Protein Digestion

  • Proteases cleave peptide linkages by hydrolysis
  • Three origins for gut proteases:
    • Gastric protease (pepsins)
    • Pancreatic protease
    • Brush border protease
  • endopeptidases - hydrolyse peptide bonds in middle of polypeptide
    • trypsin
    • chymotrypsin
  • exopeptidases - hydrolyse peptide bonds at end of polypeptide
    • carboxypeptidases
    • aminopeptidases
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Protein Digestion

  • Gastric protease (pepsin)
    • endopeptidases
    • secreted by chief cells as pepsinogen (activated by H+ and pepsin autocatalysis)
    • have acidic pH optimum
    • initiates luminal phase of protein hydrolysis
  • Pancreatic protease
    • secreted from acinar cells in response to neural and hormonal stimuli
    • secreted as inactive zymogens
    • trypsinogen, chymotrypsinogen, procarboxypeptidase
    • activated by enterokinase in small intestine
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Protein Digestion

  • Intestinal brush border protease
    • situated on apical surface of epithelial enterocytes in duodenum, jejunum and proximal ileum
    • enterokinase, oligopeptidase, aminopeptidase
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Absorption and Transport of Amino Acids

  • Products of protein digestion are:
    • tripeptides, dipeptides and amino acids
  • Further hydrolysis of tripeptides and dipeptides occurs by cytosolic peptidases within enterocytes
  • Absorption from lumen across brush-border occurs by three main mechanisms:
    • passive diffusion
    • Na+/amino acid symport
      • similar to SGLT-1 mechanism for glucose
    • Na+-independent facilitated diffusion
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Absorption and Transport of Amino Acids

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Lipids

  • Animal/dairy fats and vegetable oils
  • Most dietary fat in the form of triacylglycerols (fatty acids condensed with glycerol)
  • Fatty acids
    • Saturated (C-C single bonds) - stearic acid
    • Unsaturated (one or more C=C double bonds)
      • monounsaturated - oleic acid
      • polyunsaturated - arachidonic, linoleic, eicosapentaenoic (EPA)
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Acylglycerols

  • Monoacylglycerols (monoglycerides)
  • Diacylglycerols (diglycerides)
  • Triacylglycerols (triglycerides) - majority of dietary fat

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Phospholipids

  • Vital component of cell membranes
  • Similar in structure to triglyceride but have one fatty acid chain replaced by a phosphate group
  • Phosphate group has a substituted group attached (X), e.g. ethanolamine, choline, serine
  • Key for cell apoptosis signalling and blood clotting response
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Digestive Lipases

  • Hydrolyse triacylglycerols to fatty acids, monoacylglycerols, diacyglycerols and glycerol
  • Acidic lipases
    • gastric and lingual
  • Pancreatic lipases

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Digestive Lipases (Acidic Lipases)

  • Gastric lipase produced by peptic (chief) cells of fundus
  • Lingual lipase from serous glands of tongue (not secreted by salivary glands, but present in saliva)
  • Potent and rapidly acting lipases, pH optima 4.0-5.5
  • Initiate lipid hydrolysis in stomach (independent of bile) forming fatty acids and diacylglycerols)
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Digestive Lipases (Pancreatic Lipase)

  • Acts on diacyl- and triacylglycerols in duodenum; neutral pH optimum
  • Major hydrolysis products are fatty acids and monoacylglycerols
  • Responsible for the majority of lipid hydrolysis in adults; completes hydrolysis initiated by the acidic lipases
  • Optimal activity requires bile acids
  • Bile acids emulsify fat into small droplets maximising exposure of the glycerol 'head' structure to the enzyme
  • Colipase, a peptide co-factor, produced by pancreas
    • essential for optimum pancreatic lipase activity
    • prevents bile acids from inhibiting lipase activity
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Pancreatic Lipase

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Lipid Absorption

  • Formation of mixed micelle (mainly monoacylglycerol, free fatty acids, bile acids and cholesterol)
  • Diffusion across apical membrane of monoacylglycerol, free fatty acids and glycerol
  • Binding to fatty acid binding protein in the cytosol for transport to smooth endoplasmic reticulum
  • Re-synthesis of triacylglycerol
  • Packaging of triacylglycerol with cholesterol, apoproteins and phospholipids to form chylomicrons
  • Transport of chylomicrons across basal membrane into lacteals
  • Lipids are re-processed within enterocyte cell, unlike carbohydrate and amino acids
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Lipid Absorption

Electrolyte and Fluid Balance

  • Major regulation of fluid balance is via kidneys, GI tract, breathing and skin
  • Electrolytes have chemical bonds that allow dissociation into ions, which carry an electrical charge
  • Electrolytes are of critical importance in fluid balance, i.e. fluid balance and electrolyte balance are interdependent
  • Fluid balance can be maintained only if intake equals output

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Bidirectional Fluid Flux in the GI Tract

  • Water movement into lumen (secretion)
  • Water recovery from lumen (absorption)
  • Net absorption of water by passive movement
    • response to osmotic and hydrostatic pressures
  • Luminal fluid generally remains isotonic with plasma
  • Most solutes and water are re-absorbed in the ileum, some in the colon
  • Major mechanism is Na+-glucose co-transporter (SGLT)
    • some transcellular or paracellular passive transport
  • Malabsorption of solutes and water by ileum may overwhelm the colon's absorptove capacity
    • leads to diarrhoea and electrolyte loss
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Bidirectional Fluid Flux in the GI Tract

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Passive Electrolyte Transport

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Mechanisms of Na+ Reabsorption in Ileum

  • Most efficient absorption in the distal ileum coupled with water
  • Co-transporter mechanisms
    • glucose/galactose
    • amino acids
  • Coupling to Na+/H+ exhange
  • Passive transcellular/paracellular diffusion
  • Cl- absorption is coupled to Na+ absorption
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Absorption of Minerals

  • Divalent cations (e.g. Ca2+ and Mg2+) are poorly absorbed
    • osmotic laxactive effect - milk of magnesia
  • Ca2+ absorption by enterocytes is tightly regulated to maintain total body Ca2+ stores
  • 1,25-dihydroxy-vitamin D3 stimulates synthesis in enterocytes of Ca2+ binding protein which transports Ca2+ across the apical membrane
  • Inorganic Fe2+ is complexed with transferrin in the lumen and absorbed into enterocytes by a receptor mechanism
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Absorption of Vitamins

  • Water-soluble vitamins
    • most are absorbed by simple passive diffusion
      • vitamin C (ascorbic acid)
    • some are absorbed by specialised mechanisms
      • vitamin B12 (cobalamins) absorbed by ileal enterocyte receptors for vitamin B12-intrinsic factor complex
  • Fat-soluble vitamins
    • vitamins A, D, E depend on solubilisation by bile salts for intestinal absorption
    • dietary vitamin K (phytomenadione, vitamin K1) absorbed by active transport in ileum)
    • bacterially-synthesised vitamin K2 absorbed passively in colon
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Absorption of Water

  • Approximately 9L of fluid enter the small intestine each day
  • Approximately 2.3L are ingested in foods and beverages
    • rest is from GI secretions
  • 90% of this water is absorbed in the small intestine
  • Water absorption is driven by the concentration gradient of the water
    • concentration of water is higher in chyme than in epithelial cells
    • water moves down its concentration gradient from the chyme into cells
    • remaining water is then absorbed in the colon
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