GI lipid digestion
Terms
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- physiological function of lipids
-
membrane material
energy source & insulation
hormones
fat soluble vitamins
taste - problems with lipid digestion
-
poor water solubility- enzymes
aggregate into large complex-
contact digestive surface - flow of lipid
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chylomicrons formed in intestines
enter circ thru lymph
travel in blood vessels
deliver to tissues
return to liver
process & repackage
recirc as VLDL - lipoprotein structure
-
(to increase solubil in plasma)
cholesterol esters & triacyl glycerols in center (hydrophobic)
phospholipid outer layer
cholesterol within phospholipid (polar end out)
proteins bind PL layer for recognition - lipid transport molecules
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Chylomicrons
VLDL
LDL
HDL - characteristics of chylomicrons
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BIG
formed in intestine
transport of dietary TAG
associated with apo A, B48, C I,II,III & E - characteristics of VLDL
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formed in liver
transport of endogenous TAG
short lived (6-8 hr)
apo B100, C I,II,III & E - characteristics of LDL
-
formed in circulation (breakdown IDL)
delivers cholesterol to tissues
apo B100 - characteristics of HDL
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smallest (dense)
cholesterol "mop"
returns extra chol to liver
apo A, C I,II,III, D & E - steps in absorption of fats
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Minor digestion of TAG in mouth/stomach
Majority in duodenum/jejunum- panc enzymes
micelle formation (bile acids)-lipolytic enzymes can work
Absorption lipolytic products from the micelle into the intestinal
epithelial cell
Re-esterification to form triacylglycerols and cholesterol esters
Assembly and export of chylomicrons to lymphatics - enzymes in lipid digestion
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Pancreatic Lipase (major)
lingual & gastric lipase
(infants use gastric)
colipase
cholesterol esterase (activated by bile)
phospholipase (activated by trypsin) - pancreatic lipase
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major enzyme for lipid digestion
needs COLIPASE to activate
not zymogen in pancreas - cholesterol esterase
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activated by bile
secreted by pancreas
acts on chol esters - phospholipase
-
activated by trypsin
cleaves phospholipids
secreted by pancreas (PLA2)
hydrolize ester linkage at C2
form lysophospholipids - lysophospholipid
-
powerful detergent
product of phospholipase
aid digestion
also secreted by liver (lecithin/phosphotidylcholine) aids PLA2
in bee & cobra venom- destroy cells - product of cholesterol esterase
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1 FA and 1 cholesterol
from cholesterol ester
(have to get chol out to sfc 1st) - product of pancreatic lipase
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1st- diacyl glycerol + FA
2nd- 2 free FAs + monoglyceride
(from TAG) - mechanism of colipase
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embeds into PL surface
facilitate transfer of TG units
(knockout mouse dies) - products of linual & gastric lipase
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FFA + DAG
(from TAGs w/med chain FAs) - product of milk lipase
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FFA + glycerol
(from TAGs w/med chain FAs in SI)
regulated by bile acids - product of PLA2
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unsat FFA
lysolecithin
(from PLs w/unsat FA on pos 2- in SI)
regulated by bile salt & Ca++ - product of lipoprotein lipase
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FFA + Glycerol
(from TAGs in chylomicron or VLDL in capillaries)
regulated by apo CII & insulin - properties of olestra
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from cotton seed & soybean oils
sucrose in middle
can't be hydrolyzed
not digestible
steatorrhea, impaired vitamin uptake - properties of orlistat
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(Xenical)
lipase inhibitor
forms covalent bond (irreversible) w/serine active site
lowers LDL better
improved diabetes control (free FAs decrease ins sens)
decreased vit uptake
very effective wt loss for morbid obese - transport of FAs across membrane
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short chains diffuse b/c solubility ok
LCFAs have transporters
Acyl CoA synthetase attaches CoA to prevent rediffuse
transfer to FA Bind Protein (chaperone)
deliver to ER for resynth of chylomicrons
lacteal
capillary - LCFA membrane transporters
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CD36 (MPs & HDL R)
FATP- unknown mechanism - properties of FABP
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multiple Beta sheets
form hydrophobic pocket
delivers to smooth ER
resynth - resynthesis of cholesterol esters
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cholesterol diffuses thru membrane
ACAT (acyl chol acyl transferase)
FACoA - ACAT
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acyl cholesterol acyl transferase
re-esterifies cholesterol after absorption
uses FA CoA (to CoASH)