metabolism of LDL, IDL and HDL
- 1. METABOLISM OF LDL, IDL AND HDL Ashwathi Govind
- 2. content • Structure & function of IDL • Metabolism of IDL • Structure & function of LDL • Metabolism of LDL • Structure & function of HDL • Metabolism of HDL • Reference
- 3. STRUCTURE OF IDL Their size is in general 25 to 35 nm in diameter They contain primarily a range of TAG and cholesterol esters. Contain multiple copies of the receptor ligand ApoE in addition to a single copy of Apo B100.
- 4. METABOLISM OF IDL • Enable fats and cholesterol to move within the water based solution of the bloodstream. • Each native IDL particle consist of protein that encircles various lipids enabling as a water soluble particle these lipids to travel in the aqueous blood environment as part of the fat transport system within the body. • Promote the growth of atheroma.
- 5. IDL has two competing metabolic fates Uptake by the liver Further processing to become LDL
- 6. • Formed from the degradation of VLDL as well as HDL lipoprotein lipase • VLDL IDL LDL TAG TAG + Apo E
- 8. * Bad cholesterol cholesterol * liver peripheral tissue l
- 10. METABOLISM LDL is taken up by peripheral tissue by receptor mediated endocytosis. LDL receptor are present in all tissues. But most abundant in hepatic cells LDL receptors are located in specialized regions called clatherin coated pits. Binding of LDL to receptor is by apo B 100
- 11. LDL RECEPTORS It is a polypeptide consists of 839 amino acids. Contains extracellular and intracellular domains. Extracellular domain is responsible for the clustering of LDL receptors into regions of plasma membrane termed coated pits. Apo B100 binds to Apo B100 receptor, receptor LDL complex is internalized by endocytosis.
- 12. The endosome vesicle fuses with lysosomes. The receptor is recycles and returned to the cell surface. LDL particles, Apo proteins and cholesterol esters are hydrolyzed by hydrolases, forming free amino acids and free cholesterol. 70% of LDL is degraded in the liver and remaining is in extra hepatic tissues. Free cholesterol incorporated into plasma membrane or stored in cells.
- 14. FUNCTION OF LDL 75% of plasma cholesterol is incorporated into LDL particles. LDL transport cholesterol from liver to peripheral tissues. The transported cholesterol has following fates • For synthesis of steroids • May be incorporated into membranes • May be esterified to MUFA and stored.
- 15. Clinical significance of LDL LDL concentration is increased in cardiovascular diseases Small fraction of cholesterol is taken up by macrophages. Increased levels of LDL or modified LDL or oxidized LDL increases the fraction of cholesterol taken by macrophages.
- 16. There is an LDL infiltration through arterial wall and taken up by macrophages or scavenger cells. This is starting event of atherosclerosis leading to MI Defects in LDL receptor synthesis leads to familial hypercholesterolemia.
- 18. Structure of HDL
- 19. FUNCTION OF HDL HDL transport cholesterol from peripheral tissues to liver, called as reverse cholesterol transport Cholesterol is excreted through bile Cholesterol excretion needs prior esterification with PUFA PUFA reduces serum cholesterol levels.
- 20. METABOLISM Intestin al cells synthes is compo nents of HDL and release into blood Nascen t HDL are discoid in shape. Free cholest erol is taken up by the HDL Apo A 1 of HDL activate s LCAT. LCAT binds to HDL disc Cholest erol from cell is transfer red to HDL by cholest erol efflux regular protein, which is an ABC protein
- 21. Lecithin is a compone nt of lipid bilayer of HDL disc. Second carbon of lecithin contains PUFA This PUFA is transferre d to 3rd OH group of cholester ol to form cholester ol esters. Cholester ol esters moves into the interior of HDL disc. HDL become spherical shape with lot of cholester ol are formed This is called as HDL-3
- 22. Mature HDL are taken up by the liver cells by apo A 1 mediated receptor mechanism. HDL is taken up by hepatic scavenger receptor B1 Hepatic lipase hydrolyzes HDL phospholipid and TAG. Cholesterol esters are released into liver cells. These cholesterol esters are used for the synthesis of bile acid or excreted as bile.
- 23. When HDL3 remains in circulation, cholesterol esters from HDL is transferred to VLDL,IDL and LDL by a cholesterol ester transfer protein( CETP) TAG from VLDL,IDL and LDL is transferred to HDL in exchange for cholesterol esters HDL particle rich in TAG and spherical are called as HDL2 These particle are first acted upon by hepatic triglyceride lipase (HTGL) Efflux of cholesterol from peripheral cells to HDL is mediated by ABC transporter protein.
- 25. CLINICAL SIGNIFICANCE Serum HDL levels are inversely related to the incidence of MI HDL levels <35 mg/dl increases risk of CAD,>65mg/dl reduce the risk of CAD
- 27. Reference • Lippincott’s; fifth edition; Richard A Harvey • Biochemistry; debajyothi;13th edition • Vasudevan & Sreekumari, Text book of biochemistry for medical students.(6th Ed.). • Biochemistry; Sathyanarayana,u Chakrapani.