Digestion And Transport Of Dietary Lipids

stabilizes the phospholipid bilayer of the membranes
precursor of bile acids, physiological detergents
precursor of steroid hormones
cholesterol structure
very hydrophobic molecule because there is only one hydroxyl group and the rest is a carbon-carbon chain
converted to cholic acid (bile acid); carbon chain is shortened, carboxyl group is added to the end as well as 2 hydroxyls, and 3 beta hydroxyl becomes a 3 alpha hydroxyl
flat structure becomes bent when it is converted to cholic acid; bottom part is very hydrophilic while the top is still very hydrophobic
cholesterol absorption
cholesterol always maintains homeostasis in the body; input always balances the output
people are usually resistant to hyper- and hypocholestemia because it maintains homeostasis
dietary cholesterol transport that allows dietary cholesterol to be absorbed into enterocytes by diffusion
zetia blocks dietary cholesterol absorption in the liver through NPC1L1
combine zetia with a statin to block cholesterol absorption and cholesterol synthesis in order to lower cholesterol levels
cholesteryl ester
has to be formed to carry cholesterol through the body
combines with triacylglycerol, ApoB48, and MTP to form a chylomicron to be transported out through ABCA1 transporter
sitosterol cholesterol
plain sterol; majority of plain sterols absorb and then transport out of the intestine via ABCG5/ABCG8 transporters so we only retain about half of the cholesterol that's taken in
sitosterolemia when a patient accumulates a lot of sitosterol which is toxic; causes arthritis, early artherosclerosis
digestion of triacylglycerides
hydrolysis to fatty acids and 2-monoacylglycerol in the lumen of the intestine
limited digestion of these lipids occurs in the mouth (lingual lipase) and stomach (gastric lipase)
these lipases preferentially hydrolyze short- and medium-chain fatty acids
bile salts
emulsifies dietary fat that leaves the stomach and enters the small intestine
act as detergents, binding to the globules of dietary fat; emulsified fat is attached by digestive enzymes from the pancreas
synthesized in the liver, stored in the gallbladder, and secreted into the intestinal lumen
secreted by the intestine signals the gallbladder to contract and release bile acids and the pancreas to release digestive enzymes
stimulates gallbladder contractions in order to release bile acid (really refers to bile salt as seen in the picture)
pancreatic lipase
activated by bile acid
colipases increase lipase activity to digest triglycerides to monoacylglycerol and free fatty acids
cholesterol esterases hydrolyze cholesterol esters to free cholesterol and fatty acids
phospholipids are hydrolyzed to lysophospholipids and free fatty acids
triglycerides are transported in lipoprotein particles; intestinal cells package triglycerides together with proteins and phospholipids
contain 85% TG, Apo B-48, cholesterol esters (CE) and phospholipids (PL), and also fat-soluble vitamins
chylomicron synthesis
lipoprotein B-58 is synthesized in the RER membrane and triglycerides are synthesized in the SER membrane; combine into golgi body where they are converted into a chylomicron and excreted into lymph
ApoB48 vs. ApoB100
encoded by the same gene (very large gene)
no RNA editing in the liver so mRNA is completely translated into ApoB100
RNA editing during transcription in the intestine changes CAA in the middle of the mRNA to the stop codon (UAA) which produces ApoB48
LDL receptor recognizes ApoB100 because the binding site is towards the end of the sequence; RNA editing in the instestine causes the binding site to not be translated so the LDL receptor does not bind to ApoB48
chylomicron only carries ApoB48
dietary lipid transport
chylomicrons (CM) are triglyceride-rich; nascent CMs are secreted into the lymphatic system, enter the blood through the thoracic duct, and receive ApoCII and ApoE from HDL in blood to form mature CM
ApoE is recognized by membrane receptors, LDL receptor-related proteins (LRPs)
ApoCII activates lipoprotein lipases (LPL) located on the surface of capillary endothelial cells in muscle and adipocytes, and digest triglyceride to release free fatty acids from CM and VLDL