HNF 461 1st Edition Lecture 21 Outline of Last Lecture I Lipoprotein System II Structure of VLDL III In the Hepatocyte a Fed State b Fasting State IV Formation of VLDL V LPL Regulation VI Regulation of VLDL VII In the Adipocyte a Fed State b Fasting State VIII Albumin Bound Fatty Acids Outline of Current Lecture I General functions of LDL and HDL II Structure of LDL and HDL III LDL Transport into Cells IV Synthesis of Cholesterol from Acetyl CoA V HDL Synthesis VI Exchange of TG and CE Between VLDL LDL and HDL VII Cholesterol Homeostasis Current Lecture LDL and HDL 1 General functions of LDL and HDL a Transport glycerol around the body 2 Structure of LDL and HDL These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute a LDL apoprotein B100 is the only protein attached to surface contains high proportion of cholesterol b HDL contains high proportions of lipoproteins and phospholipids phospholipids can attract cholesterol from other cell departments 3 LDL Transport into Cells a Receptor mediated Endocytosis LDL molecule binds to receptor on cell surface When bound cell will form invagination to engulf LDL Lysosome in cell will release free amino acids and cholesterol from LDL b If an endocrine cell cholesterol is used to make hormones c Extra amounts of cholesterol will be transported to cell ER and then esterified to cholesterol esters and stored in the cell d If a Liver cell Use cholesterol to make bile acid or bile salt e Cholesterol Homeostasis within cell monitored by HMG CoA Reductase and ACAT i ACAT catalyzes storage of cholesterol in cell 4 Synthesis of Cholesterol from Acetyl CoA a Starts with Acetyl CoA b Requires NADH and ATP c Requires HMG CoA Reductase can be inhibited by cholesterol AMPK phosphorylates inactivates when cell is low in energy 5 HDL Synthesis and Transport a Synthesized in the liver b Once it is made has apoA1 as component critical structural component of HDL without apoA1 HDL cannot be made c Nascent HDL LCAT apoA1 and apoC2 d ABCA1 responsible for transport of cholesterol to HDL e SR B1 transfers lipids to and from HDL f LCAT takes long chain fatty acids and moves them onto the cholesterol molecule to esterify it makes cholesterol more hydrophobic so it moves from the surface of HDL to the core Without apoA1 LCAT cannot esterify cholesterol g HDL3 Particle intermediate between nascent HDL and HDL2 cholesterol poor h HDL2 Particle cholesterol rich once cholesterol has been transported packed into HDL transported to the liver i Once HDL is in the liver cholesterol is used to make bile acids salts cholesterol is excreted via bile 6 Exchange of TG and CE Between VLDL LDL and HDL a CETP protein that facilitates exchange of TG CE between HDL and VLDL LDL i Not all species have protein humans rabbits and mice do b Bidirectional exchange helps to maintain equilibrium between particles i Particles with high TG VLDL LDL give away to particles with low TG ii Particles with high CE HDL give away to particles with low CE c Transport of cholesterol from HDL to LDL can facilitate the formation of plaques 7 Cholesterol Homeostasis a Single Cell Uptake of Cholesterol i Makes it by itself ii Uptake from LDL b Removal of Cholesterol by Single Cell i Transport of cholesterol to HDL ABCA1 protein ii Self regulation c Liver Uptake of Cholesterol i ILD LDL from peripheral tissues ii Dietary cholesterol by chylomicron remnants iii HDL binding to SRB1 receptor d Removal of Cholesterol from Liver i Bile acids salts excreted into the intestine 5 cholesterol will be excreted via feces
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