digestion and absorption of lipids Flashcards
Types of cholesterol
esterified cholesterol only found in liver and blood foods; unesterified cholesterol in everything else
emulsification
Formation of oil droplets in water
How does emulsification happen?
Chewing, gastric churning, intestinal peristalsis between pyloric sphincter and duodenum
With each mechanical process size of oil droplet decreases
With decrease in size comes increase in surface area
How are emulsions stabilized?
Emulsions are stabilized by a monolayer at the interface formed by dietary and secreted lipids.
Lipases
Enzymes responsible for hydrolysis of lipids
Present in aqueous lumen at oil-water interfaces
Gastric lipase- when active? resistance/ inactivation?
Only active and stable at approx. pH 4
Resistant to Pepsin
Inactivated by Pancreatic Proteases in bile salts in small intestine
(Pancreatic deficiency would result in extended activity into duodenum)
gastric lipase action
Cleaves a fatty acid from TAGs
Results in:
- one protonated FFA (free fatty acid)
(Those that are medium and short chain move into portal blood through gastric mucosa)
- one diacylglycerolpancreatic lipase- where secreted, what dependent upon?
Major lypolytic enzyme of pancreatic secretions
Secreted into duodenum
Secreted in huge excess
Dependent on:
Presence of Colipase, Alkaline pH of small intestine, Calcium, Bile Salts, Fatty acid substrate
Action of pancreatic lipase
At Oil-Water interface colipase necessary here to reduce inhibition from phospholipids or proteins on micelle surface Hydrolyze all TAGs Results in: 2 FFA 1 MAG
dietary lipids
Most dietary lipids are ingested as triglycerides
Must be degraded into FFA and MAGs to be taken up
Xenical and Alli (orlistat)
inhibit degradation of lipids by inhibiting Pancreatic Lipase.
Phospholipase A2
Pancreatic-Secreted as proenzyme
Requires: bile salts, alkaline pH
Action: Cleaves a FFA from a glycerophospholipid, Leaves a lysophospholipid , no middle fatty acid
In small intestine
In large intestine all from bacteria
Carboxyl Ester Hydrolase
Not substrate specific
Hydrolyzes all esters
Releases free: Cholesterol, Glycerol
Same action as bile-salt stimulated milk lipase
Bile-salt Stimulated Milk Lipase
In human milk for infant fat digestion
Stable through gastric acidity but not active
Active at alkaline pH of duodenum and jejunum
Action:
Hydrolyzes:
DAGs, MAGs, TAGs, fatty esters
CCK
Stimulated release by free fatty acids in duodenum
Stimulates bile flow into duodenum
Stimulates secretion of pancreatic enzymes
pancreatic lipase
pancreatic esterase
Lipids in stools
Intact acylglycerols rarely found in stools Even in severe cases of malabsorption Due to bacterial digestion in colon Sudan III Staining Chemical test for stool fat
How are medium chain fatty acids absorbed?
Medium-chain fatty acids are absorbed independently of micelles or bile salts
Once inside the enterocyte they are directly transferred into blood
Important fat substitute for patients with related malabsorption
Emulsion Droplets
Absorb products and components of lipid digestion
Multilamellar until budding of mixed micelles.
Multilamellar
multiple lipid bilayers
unilamellar
one lipid bilayer
micelle
lipid monolayer with tails facing the hydrophobic core
Surface components of emulsion droplets
cholesterol
MAGs
lecithins
pancreatic lipases
bile salts
Built up around surface, assist in formation of the unilamellar vesicle
Liquid crystalline layer made of bile salts, surface components and Ca2+ rich fatty soaps.
core lipids of emulsion droplets
undigested lipids:
DAGs
TAGs
cholesterol esters
What happens to emulsion droplets as they move through digestion
MAGs are hydrolyzed on the surface by lipases and free fatty acids are released.
DAGs and TAGs from the core replace the surface MAGs.
The droplet decreases in size, thereby increasing its surface area and facilitating more hydrolytic digestion by surface lipases.
Micelle formation
Increased deposition of the liquid crystalline layer causes budding of multilamellar vesicles from the emulsion droplet.
Bile salts convert the multilamellar vesicle to unilamellar.
The addition of more bile salts assists micelle formation.
Microclimates of the intestine
bulk water layer
mucous gel layer
unstirred water layer
enterocyte apical membrane
Bulk water phase of the lumen
where hydrolysis and micelle formation take place
Mucous gel layer
lines the epithelial surface
provides a barrier to diffusion by proteins called mucins
Unstirred water layer
juxtaposed to cell membranes
in disequilibrium with bulk water phase due to mucous gel
allows for diffusion of short and medium chain fatty acid monomers directly into enterocytes
larger fatty acids are partitioned back into micelles present
micelles present maintain high concentrations of lipids in unstirred layer because lipids diffuse from micelles in this protonated environment
enterocyte apical membrane
micelles do not diffuse across membrane therefore lipids must leave micelle
Na/H exchangers maintain a protonated microenvironment in unstirred layer
Fatty acid translocases and fatty acid binding proteins enhance translocation and preferentially bind long-chain fatty acids which do not easily diffuse
What happens inside the enterocyte
Re-esterification
Packaging into lipoprotein particles
Re-esterification
Smooth Endoplasmic Reticulum (SER)
long chain fatty acids are assembled back into TAGs and phospholipids
Packaging into lipoprotein particles
Rough Endoplasmic Reticulum (RER)
Apolipoproteins are synthesized and trafficked to SER and Golgi
What happens in the smooth endoplasmic reticulum
Apolipoproteins encounter TAGS, phospholipids and cholesterol esters in SER and form
Chylomicrons
The largest lipoprotein made primarily of TAGs
Surface coated with lecithin and phospholipids
Very-low-density lipoproteins (VLDLs)
Carry mainly endogenous lipids during both fed and fasting states
Trafficking of lipoprotein particles
SER:
Vesicles carry chylomicrons and VLDLs to Golgi cis face
Golgi Apparatus:
Apolipoprotein A-I associates with them here
Glycosylation of Apolipoproteins occurs
Vesicles carry chylomicrons and VLDLs from Golgi trans face to the basolateral membrane
What happens in the lymph
Secreted chylomicrons and VLDLs enter lymph through lymphatic capillaries
They are too large to pass through fenestrae
Through lymph capillaries they enter the cisternae chyli
Through the cisternae chyli they enter the thoracic duct
Through the thoracic duct they enter the blood via the left subclavian vein
Water Soluble vitamins
Absorbed in small intestine
Have specific carriers and/or brush border and luminal enzymes for deconjugation or phosphorylation
Many Na+ dependent
Many utilize GPCR and cAMP
Fat-soluble vitamins
Called so because of chemical structure and storage in fat deposits
Rely on the lipid absorption process because of chemical structure
Digested from protein carriers by proteolysis of gastric juices
incorporate into emulsion droplets in small intestine
Taken up by enterocytes via simple diffusion or through transporters
What happens with vitamins in the enterocyte
Diffuse to SER
Can occur through specific carrier proteins
Ex. Retinol-binding protein
Associate with lipid droplets to form chylomicrons or VLDLs
Translocate to Golgi
Translocate into lymph
What happens with vitamins in the lymph
Enter systemic blood
Enter the liver through receptor mediated endocytosis of chylomicrons
Fat-soluble vitamin deficiencies
Can occur from malabsorption Bariatric surgery drugs that impair hydrolysis drugs that impair bile acids impaired hepatobiliary function unabsorbable fat substrates Treatment: Water-miscible emulsions of the vitamins
Folate
Deficiency can cause neural tube defects in developing fetus
Spina bifida and anencephaly
Tetrahydrafolate
Reduced form of folate
Biochemically active form
Cofactor
Synthesis of thymine and purines
Deficiency of tetrahydrafolate results in…
Inhibited DNA synthesis
Megaloblastic Anemia
Red blood cells in bone marrow become large due to uninhibited protein and RNA synthesis
treatment of tetrahydrafolate deficiency
pteroylmonoglutamate (PteGlu1)
Digestion of folate
Folate exists in food as folate polyglutamate (PteGlu7)
Folate conjugase
Removes glutamate residues one by one to PteGlu1
Transported into enterocytes by PteGlu1 Carrier
Occurs in small intestine
Mechanism of movement through basolateral membrane unknown
In liver:
enzymatically change it to THF
Vitamin B12 (Cobalamin)
Only synthesized by microbes
Found in animal products
vegetarians at risk
Coenzyme
transfers a methyl group onto homocysteine to create methionine
Methionine an essential aa
During deficiency of methionine the body uses intracellular stores of folate
Folate and B12 deficiencies cause same megaloblastic anemia
Absorption of vitamin b12
Released from protein carriers in stomach via pepsin and low pH
Bound by haptocorrin in stomach
Intrinsic factor
Also secreted in stomach
Does not interact with cobalamin until it reaches small intestine
HCO-3 secreted by pancreas induces release of cobalamin from haptocorrin
cobalamin binds to IF
Cobalamin-IF binds receptors on apical surface of enterocytes in ileum
Once in the enterocyte
Cobalamin and IF dissociate
Binds transcobalamin II
Required for basolateral exit
Delivered through hepatic circulation to liver
The liver secretes excess cobalamin into bile
The dietary intake is so low the bile and diet cobalamin in small intestine is equal
Vitamin B12 Deficiency
Can occur from a vegetarian diet
Pernicious anemia
in elderly, caused by lack of parietal cells
can be due to atrophy or Ab-mediated immune response against parietal cells or IF
no IF secretion
no absorption without IF
Bacteria in small intestine can bind and metabolize it
Crohn disease
Ileal resection
