Physiology - GI - DIGESTION AND ABSORPTION - LIPIDS

  1. _______ are the most abundant dietary fat.
    Triglycerides
  2. Lipid digestion is promoted in the GI lumen primarily through the combined efforts of ______, the solubilizing properties of ____ and the enzymatic activity of _______.
    • GI motility
    • bile
    • pancreatic lipases
  3. Lipid digestion products become incorporated into _______ that transport them along the small intestine and to the intestinal ______.
    • micelles
    • brush border
  4. lipid digestion products ____ from the _____ and are transported across the apical membrane by _______ through the _______ or by ________.
    • diffuse
    • micelles
    • passive diffusion
    • lipid matrix
    • specialized membrane transporters
  5. The most active sites for lipid absorption are _________. Most lipid digestion products are absorbed by the time they reach _______.
    • duodenum and jejunum
    • mid jejunum
  6. In the cytosol the products are _________ and transported across the basolateral membrane. They subsequently enter the _____ and ultimately the circulatory system.
    • reprocessed, repackaged
    • lymph
  7. Compare lipid digestion in the mouth and stomach and discuss the importance of the primitive and fine emulsions.
    • mouth:
    • crude emulsification
    • mechanical: chewing -> reduce particle size
    • lingual lipase

    • stomach:
    • lingual+gastric lipase (still minor)
    • mixing churning: reduce droplet size to 1um

    • high surface area for enzymatic digestion
    • solubility
  8. Discuss lipid digestion in the small intestine by pancreatic lipase (glycerol ester hydrolase) and colipase. List the major digestion products.
    lipase: active when secreted; ineffective along; blocked by bile salts; needs colipase

    colipase: inactive when secreted by pancreas; converted by trypsin; replaces bile salt at the droplet surface and binds lipase; the complex cleaves off FA from droplet

    2FAs, monoglyceride
  9. Identify the intestinal absorption sites for final lipid digestion products and describe the mechanisms of transport across the brush border. Describe the unstirred layer and explain its influence on lipid absorption.
    mid jejunum

    glycerol - free, diffusion across tight junction into cytosol

    short/mid chain FAs - protonated at unstirred layer; released from mixed micelle; passively diffuse across membrane.

    longer chains - MVM-FABP actively transport across; down Na gradient

    cholesterol - NPC1L1
  10. Discuss the importance of fatty acid binding (FAB) proteins, β-lipoproteins and chylomicrons in lipid absorption. Describe the transport of reprocessed lipids across the basolateral membrane and their entry into the blood.
    • FAB transport FA to desired reprocessing location: ER
    • FA reesterfied at ER to triglycerides and reassembled to droplets, prechylomicron.
    • prechylomicron diffuse to golgi, receives apoB coating from β-lipoproteins, becomes chylomicron
    • exocytosis->lateral space-> lymph->->thoracic duct-> blood
  11. Discuss general causes of lipid malabsorption. Define steatorrhea and describe its symptoms and causes.
    • high duodenal pH
    • low pancreatic lipase
    • low pancreatic lipase activity
    • inadequate micelle caused by insufficient bile salts
    • damage to absorptive surfaces (Celiac desease)
    • bacteria overgrowth-deconjugation of bile salt
    • failure to synthesize apoB, no chylomicron

    • fat in stool
    • malnutrition
  12. Lipids
    - Sources
    - composition
    - diet (plants and animals), internal cholesterol synthesis, dead bacteria

    • - 95% (of the dietary intake) triglycerides
    • - 5% phospholipids (glycerol phospholipids)
    • - sterols, cholesterol, cholesterol esters
    •     - NOT fatty acids but derived from and metabolized like fats
  13. Lipids digestion - Mouth
    - function
    - types
    - end products
    - crude emulsification

    • - chewing – particle size reduction
    • - mixes fats with lingual lipase (Ebner’s glands (tongue) > hydrolysis
    •     - activity continues into stomach

    - glycerol and fatty acids (10%)
  14. Lipids digestion - Stomach
    - first chemical digestion of triglycerides (lingual lipase?)

    • - primitive emulsion – mixing churning - suspension small droplets in water
    •     - increases surface area - oil-water interface
    • - digestion
    •     - lingual lipase - triglycerides
    •     - gastric lipase (from chief cells) - triglycerides - attack droplet surface
    •         – fragments smaller but droplets still large
    •     - gastric acidity – inhibits optimal emulsion
    •     - gastric motility - continues to reduce droplet size and increase the surface area
    •         - final size about 1 um - can be digested by pancreatic enzymes
    •              - oil-water interface

    • - gastric emptying – carefully regulated
    •     - prevent dumping syndrome [rapidly loading small intestine w/ hypertonic contents]
    •     - slowed by CCK - duodenum
    •     - CCK increases motility
    •     - More time for mixing, emulsion formation, and lipid digestion
    •          - Cooperation between stomach, motility, and duodenum
    •          - Slowing prevents duodenum from being overwhelmed with undigested fats
  15. Lipid droplets of the crude emulsion are emptied into the ________. In the small intestine, they are emulsified by the combined activity of ________ and _______.

    Further digestion with _______ produce ______________, which are incorporated into the .
    • duodenum
    • bile salts
    • intestinal motility

    • pancreatic lipases
    • free fatty acids and monoglycerides
    • mixed micelle
  16. major site for lipids digestion - ______   
    - lingual and gastric lipases ________
    • duodenum and jejunum
    • degraded by duodenal alkalinity
  17. Digestion in the Small Intestine
    • - fat droplets enter small intestine as crude emulsion
    • - crude emulsion - converted to fine suspension, essential for water soluble pancreatic enzymes
    •     - Bile salt micelles - prevent aggregation
    •          - decrease surface tension - emulsify droplet
    •          - increase surface area for pancreatic enzyme attack
    •     - Motility: reduces fragments to 1 um
    • - bile and pancreatic lipases - complete digestion process
    • - final products are free fatty acids and monoglycerides
    •       - incorporated into mixed micelle
  18. The major dietary intake of lipids consists of __________.

    Primary pancreatic lipases, _________, digest the lipids by ________.
    triglycerides, phospholipids, cholesterol and cholesterol esters

    • lipase
    • phospholipase A2
    • cholesterol esterase
    • cleaving off 1-2 fatty acid per lipid molecule
  19. Pancreatic Lipase for tryglyceride
    - Glycerol Ester Hydrolase or Glycerol Ester Lipase

    • - secreted into duodenum in active form - active pH 5-8
    •     - produces 2-monoglycerides and FAs

    • - alone is ineffective emulsifier
    •     - bile salts bind to droplet surface
    •         - prevents lipase binding and digestion
    •     - enzyme needs helper - Colipase
  20. Colipase
    • - helper of lipase
    • - secreted as proenzyme (procolipase) from pancreas
    •     - activated by trysin

    •                                   trypsin
    • Procolipase (pancreas) -----------> Colipase
  21. Actions of Colipase
    • - displaces bile acids from droplet surface
    • - becomes an anchor to bind pancreatic lipase
    •     - colipase-lipase complex cleaves fatty acids from droplet
    •     - final products - 2 FAs 1 monoglyceride
    • - binds to micelle
    •     - keeps it near droplet
    •     - facilitates removal and solubilization of digested fat (only need to diffuse over a short distance, come off droplet -> absorbed into miscelle)

    • - complex - specific for triglycerides
    •     - enzyme works fast can digest fat in 1-2 minutes

    • - end products – 2 free fatty acids, 1 monoglyceride
    •     - products enter micells
  22. Phospholipase A2
    - secretion
    - substrate
    - specificity
    - final products
    • - secreted as proenzyme, activated by trypsin
    • - major enzyme for digestion of phospholipids
    • - nonspecific
    • - FAs, glycerols, monoglycerides formed, become soluble in the micelle
  23. Cholesterol Esterase
    • - secreted as active enzyme
    • - nonspecific, less active than lipase
    • - dietary cholesterol - present as a cholesterol ester
    • - cholesterol only absorbed as free sterol
    • - final products - fatty acids, cholesterol
  24. Micelles
    • - intestinal lumen carriers
    • - incorporate digestion products
    • - no glycerol and water soluble lipids

    • - very small - 5 nm diameter
    • - mixed micelle - 20-30 molecules
    • - lipid core
    • - surface lined with bile salts
  25. Lipids digestion complete by _______.
    mid jejunum
  26. Motility for FA absorption
    • brings mixed micelles near membrane
    •     - Diffuse down concentration through the unstirred layer
  27. FA absorption at Apical Membrane
    • - micelle encounters unstirred layer (boundary condition; border between well-mixed lumen and brush border)
    •     - 40 - 200 μm thick
    •     - slightly acidic layer
    •         - protonates fatty acid
    •         - micelles release fatty acid products
    •         - area saturated with fats
    •         - released products diffuse to brush border - absorbed
    • - bile salts - remain behind
    •     - absorbed by special transporters at terminal ileum
    •     - reenter circulation
  28. Apical membrane absorption
    • - glycerol, short and medium chain fatty acids (<= C12) – water soluble -
    •     - passive absorption through tight junctions -> -> portal circulation
    • - Longer chains: require transport proteins
    •     - MVM-FABP - Microvillous Membrane Fatty Acid Binding Protein
    •         - actively transports - down Na+ gradient
    •     - cholesterol - bind to FABP protein
    •         - (NPC1L1) - Niemann Pick-1-like 1
    •         - site of pharmacological blocking; Used to treat hypercholesterolemia
  29. Cytosolic Reprocessing and trafficking - Problems
    • Product Problems
    • - lipid droplet formation in cytosol
    • - some forms cell toxic
    •     - back diffusion across apical membrane
  30. Cytosolic Trafficking
    • (FAB) proteins - Primary cytosolic transporters
    • - I - FAB Proteins – nonspecific
    •     - high affinity - long chain FAs
    •     - concentrated in proximal jejunum cytosol 
    • - SCP - sterol carrier proteins
    •     - bind cholesterol and sterols
  31. Cytosolic Processing/Packaging - Endoplasmic Reticulum
    • - receives some lipids from carrier proteins
    • - lipids re-esterified to triglycerides
    • - reassembled as droplets = prechylomicrons
    • - diffuse to Golgi
  32. Cytosolic Packaging - Golgi - further packaging
    • prechylomicron
    • - receives Apo β protein coating (essential for absorption)
    • - coated droplet - chylomicron
    • - like very low density lipoprotein (VLDL)
    • - primary and last cytosolic lipid transporter
    •     - contains triglycerides, phospholipids, cholesterol
  33. Chylomicrons - Basolateral Transport
    • - large particles - 60 - 750 nm diameter
    • - fuse with basolateral membrane and exocytosed -> lateral interstitial space -> lymphatics (too big to enter capillary; lacteals permeable) -> venous circulation via thoracic duct
    • - largest particle in blood
  34. Steatorrhea
    • fat in stool; multiple causes
    • 1) increased duodenal acidity
    • 2) inadequate pancreatic lipase – major
    •     - pancreatitis, cystic fibrosis
    • 3) inadequate pancreatic lipase activity - acid pH
    •     - ZES (Zollinger-Ellinger Syndrome) - gastrin secreting gastrinoma
    • 4) inadequate micelles - insufficient bile salts
    •     - ileal resection – lack of bile recycling
    • 5) damage to absorptive surfaces
    •     - Celiac disease
    • 6) bacterial overgrowth - deconjugation
    • 7) abetalipoptrotenemia - failure to synthesize apoB (covers chylomicron)
    •     - Chylomicrons do not form or get transported out of cell

    • consequences
    • - nutritional deficiencies

    • treatment
    • - feed medium and short chain fatty acids
Author
akhan
ID
315942
Card Set
Physiology - GI - DIGESTION AND ABSORPTION - LIPIDS
Description
Physiology - GI - DIGESTION AND ABSORPTION - LIPIDS M Stout
Updated