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Lipoproteins metabolism lecture note .pptx
- 2. Lipid has hydrophobic and hydrophilic O H CH3 CH3 CH3 CH3 C H3 H H O H CH3 CH3 CH3 CH3 C H3 H H FA OH
- 4. Lipoproteins Lipoprotein any of a group of soluble proteins that combine with and transport fat or other lipids in the blood plasma. Consist of : Core of TG and CE Surface of phospholipids and some cholesterol Apolipoproteins (regulators of LP metabolism) Types CM, VLDL, IDL, LDL, HDL
- 6. B48 Chylomicron Carry cholesterol esters Lacks LDL recpt binding domain B100 VLDL,IDL,LDL Binds LDL recpt. C-II Chyl. VLDL, IDL, HDL Activates LPL C-III Chyl. VLDL, IDL, HDL Inhibits LPL E Chyl. Remnant, VLDL, IDL Binds LRP HDL A-1 HDL/Chylomicron LCAT activator (lecithin:cholesterol acyltransferase) Type Association Function
- 7. Lipid metabolism occurs in three major areas Intestine Liver Extrahepatic tissues (Muscle and adipose tissue)
- 8. Chylomicron
- 9. Lipolysis is controlled by hormone sensitive lipase:- TAG of adipose tissue is hydrolyzed by a hormone sensitive lipase to give glycerol and free FAs. Glycerol diffuses into the blood, to the liver and kidney which have glycerol kinase enzyme, so they can utilize glycerol. The free FAs can be activated to acyl CoA by acyl CoA synthetase enzyme and re-esterified with glycerol-3-p Thus, there is a continuous cycle of lipolysis and esterification When the rate of lipolysis is greater than the rate of re- esterification, free FAs diffuse into the plasma, and raise the concentration of plasma free FAs
- 10. Questions What are the lipids carried by CM? Where is CM formed? What is the source for lipids in CM? How does the CM release FFA? What is the fate of the FFA and Glycerol? Where is the LPL found? What are the components of Remnant CM?
- 11. TG/CE B48 cholesterol (exogenous) CE/TG B100 Dietary Carbohydrate glucose pyruvate Acetyl CoA mitochondria Acetyl CoA TG FFA FFA TG VLDL LIVER VLDL CMr Cholesterol (endogenous) E LDL receptor Plasma VLDL Assembly
- 13. LDL Lipoprotein lipase Capillary wall (endothelial surface) Tissues This animation shows how VLDL are metabolised once they enter the circulation from the liver VLDL B100 CII E B100 Some LDL taken up by liver (LDL receptors) Some LDL taken up by other tissues (LDL receptors). LDL delivers cholesterol and TAG to the extra hepatic tissues. Having lost TAG to tissues LDL contains a large proportion of cholesterol/cholesterol esters
- 14. QUESTIONS Where is VLDL formed? What are the lipids Carried by VLDL? Which lipid is delivered by VLDL? What is the mechanism of FFA release from VLDL? What is the fate of Remnant VLDL?
- 16. Cholesterol uptake down regulates the cells own production of cholesterol and down regulates LDL receptor synthesis
- 17. Questions How is LDL formed? What is IDL? How is CE transferred from HDL to IDL?
- 18. Dietary Regulation of Lipoprotein Synthesis Intestinal Epithelium Chylomicron Dietary Fat (+) Chylomicron Synthesis VLDL Synthesis (Liver) Glucose VLDL High CARB Insulin (+) Acetyl CoA FA/TG (+)
- 19. HYPERLIPIDEMIA Major CV risk factor - 25% of population LDL, Total Cholesterol., Total Cholesterol/HDL, all predict CVD Reducing LDL with diet or drugs, prevents CVD, saves lives, time and money. Statins, fibrates, niacin, bile acid binding resins
- 21. high density lipoprotein (HDL) Site of synthesis:- liver and intestine Function:- 1- Act as a reservoir of apo CII which is transferred to chylomicrons and VLDL to activate the lipoprotein lipase. 2- Removes free cholesterol from peripheral tissue (reverse cholesterol metabolism) (good cholesterol) and esterifies it using LCAT enzyme. Lecithin + cholesterol 常常常常 Lysolecithin + cholesterol ester 3- It transfers cholesterol to VLDL, LDL and the liver. Structure :- Lipids:- Contains mainly phospholipids together with free or esterified cholesterol. Proteins:- including apo A, apoC and apoE.
- 22. Metabolism:- Nascent HDL is the newly synthesized HDL, it consists of discoid phosoholipid bilayers containing apo A and free cholesterol. Both apo C and apo E are synthesized in the liver and transferred from the hepatic HDL to intestinal HDL when the latter enters the plasma. The transport of cholesterol from tissues to the liver is known as reverse cholesterol transport and is mediated by HDL cycle as follow; The smaller HDL3 accepts cholesterol from the tissues via the ATP binding cassette transporter-1 (ABC-1) (transporter proteins that couples hydrolysis of ATP with transport). HDL is converted to the less dense HDL2 (spherical shape) by accepting free cholesterol and esterifying it by LCAT.
- 23. HDL Metabolism
Editor's Notes
- #13: VLDL synthesised in the liver with apoprotein B100. VLDL receives apoproteins CII and E from HDL. Like chylomicrons, VLDLs travels around the circulatory system until they associate with lipoprotein lipase, an enzyme bound to the endothelial surface. This association is mediated through apoprotein CII. The lipoprotein lipase hydrolyses the triacylglycerol to liberate free fatty acids which diffuse into the local tissues. As triacylglycerol is lost, the VLDL shrinks and forms LDL. The released fatty acids can be reassembled into triacylglycerols for storage as fat or oxidised to produce ATP. The LDL return apoprotein CII and E to HDL and are taken up by receptor mediated endocytosis by the extra hepatic tissues (with some being taken back up by the liver). LDL having lost most of their triacylglycerols are rich in cholesterol and cholesterol esters and represent the route by which cholesterol is transported form the liver to the tissues (although all tissues can make cholesterol to some extent). As VLDL particles are transported in the bloodstream, Lipoprotein Lipase catalyzes triacylglycerols removal by hydrolysis. With removal of triacylglycerols and some proteins, the % weight that is cholesterol esters increases. VLDL are converted to IDL, and eventually to LDL. VLDL IDL LDL The lipid core of LDL is predominantly cholesterol esters. Whereas VLDL contains 5 Apoproteins types (B-100, C-I, C-II, C-III, & E), only one protein, Apoproteins B-100, is associated with the surface monolayer of LDL. Cells take up LDL by receptor-mediated endocytosis. The cholesterol in LDL is then used by cells, e.g., for synthesis of cellular membranes. The LDL receptor was identified by M. Brown & J. Goldstein, who were awarded the Nobel prize. The LDL receptor is a single-pass transmembrane glycoprotein with a modular design. Function is to transport endogenously synthesised TAG to the extra hepatic tissues where it can be stored as fat or to muscles where the constituent fatty acids can be used for energy. The cholesterol is delivered to extra hepatic tissues once VLDL has been metabolised to LDL