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Lecture 31

MCB 2000 Lecture 31: LDL and Cholesterol

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University of Connecticut
Molecular and Cell Biology
MCB 2000

Wednesday, April 19, 2017 MCB 2000 Lecture - Dietary and newly synthesized triglycerides transported to adipose tissue for storage packaged as lipoprotein particles • • lipoproteins are the carriers of most lipids in the body • lipoprotein - a cluster of lipids, often with a monolayer membrane, together with an apolipoprotein - cholesterol will not be on this exam - triglycerides made in liver - where most fatty acid synthesis after a meal happens - adipose tissue does some, mostly in the liver - liver is not a storage place - must be transported to adipose tissue - triglycerides are very hydrophobic -> must be packaged in lipoproteins - cholesterol is amphipathic -> will be used by many tissues - chylomicron -> small intestine makes this - very low density lipoprotein (VLDL) will transfer newly synthesized triglycerides, is made in the liver - fat in the diet is packaged as a triglyceride - lipoprotein lipase -> activated by insulin, in capillary walls - fatty acids will be split off glycerol backbone -> will be taken up by skeletal muscle and oxidized for energy, or will be reesterified in the adipose (will link fatty acids back to glycerol backbone) - glycerol will recycle back to the liver, liver has glycerol kinase, will add a phosphate, glycerol phosphate will be used for attaching fatty acid after cleaving phosphate or will keep phosphate 1 Wednesday, April 19, 2017 - insulin will stimulate lipoprotein lipase -> either release of fatty acid from dietary triglycerides (chylomicrons) or newly synthesized from VLDL - fatty acid goes to adipose cell, gets CoA attached to them, becomes triglyceride - VLDL becomes a more dense particle after unloading of TG, intermediate density lipoprotein -> low density lipoprotein -> transports cholesterol, is the bad cholesterol - cholesterol synthesis -> occurs in the liver - cholesterol precursor for steroid hormones, bile salts, vitamin D, component of membranes - requirements for cholesterol biosynthesis in fed state: • acetyl CoA - hydrolysis of high energy thioester bonds • ATP - needed for activation step, formation of activated isoprene units • NADPH - begins in the cytosol with the synthesis of mevalonate from acetyl-CoA - thiolase, HMG-CoA synthase makes HMG-CoA - reduce carbonyl to hydroxyl - HMG-CoA reductase is rate limiting step - statin drugs are competitive inhibitor
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