1. PLASMA LIPOPROTEINSDR MUHAMMAD MUSTANSAR

2. Plasma LipidsPlasma lipids are usually measured after 12 hoursfasting. The mean value of plasma lipids is 470 mg/dl.The different types of Plasma lipids are : Triglyceride normal range 50 150 (mean value 100 mg/dl)Cholesterol normal range 100 200(mean value 150 mg/dl)Phospholipids normal range 150 250 (mean value 200 mg/dl)Free fatty acids normal range 10 30 (mean value 20 mg/dl)2 3. Lipid transport in the circulationLipids are insoluble in plasma. In order to be transported they are combinedwith specific proteins to form lipoproteins: Proteins (apoproteins)HOO Non polar lipids in coreCholesterolR(TAG and cholesterol esters)ORHOH HOApoproteins are only weakly associated with a particular lipoprotein and areeasily transferred to another lipoprotein of a different class. Apoproteins havevarious functions including: Structural role Binding sites for receptors Activators or co-enzymes for enzymes involved with lipid metabolism 4. Plasma LipoproteinsAll Lipids in plasma are transported in the form lipoproteins.Any lipoprotein has: central core: formed of non-polar lipids (triglycerids &cholesterol esters). outer layer: formed of themore polar lipids(phospholipids & non-esterified cholesterol), andproteins (apoproteins) 5 5. Structure of lipoprotein INTEGRAL APOPROTEINS MONOLAYER OF PHOSPHOLIPIDCHOLESTEROLAND CHOLESTERLOL COREESTERSTRIGLYCERIDES PERIPHERAL APOPROTEINS 6. ApoproteinsAre either peripheral (can be transferred) or integral (cannot be transferred).Function:Theyact as activator for the enzymes that act on lipoproteinsThey are important for receptor recognition to uptake the lipoproteins by certain tissues.7 7. General Functions of Lipoproteins1. Keep lipids soluble as they transport them in plasma2. Provide an efficient mechanism for delivering their lipid content to tissues8 8. Plasma lipoproteins can be separated into differentfractions by two methods, electrophoresis andultracentrifugation.Ultracentrifugation ElectrophoresisNon-mobile Chylomicrons fraction VLDL -lipoproteins LDLPre - lipoproteinsHDL - lipoproteinsFree FA Albumin (+) 9 9. 10 10. The five classes of lipoprotein (all contain characteristic amounts TAG, cholesterol, cholesterol esters, phospholipids and apoproteins) DiameterMajor apoliproteinsClass(nm)Source and functionChylomicrons 500Intestine. Transport of A, B48, C(I,II,III) E(CM) dietary TAG Very low density43Liver. Transport ofB100, C(I,II,III) , EIncreasing density lipoproteins endogenously synthesised(VLDL) TAG Low density lipoproteins22 Formed in circulation by B100 (LDL)partial breakdown of IDL. Delivers cholesterol to peripheral tissues High density lipoproteins8 Liver. Removes usedA, C(I,II,III), D, E(HDL)cholesterol from tissuesand takes it to liver.Donates apolipoproteins to CM and VLDL 11. &% Types ofLipoproteinsLipid ContentOriginapoproteins2% TAG 90% (Main lipid) Chylomicrons A, B48, C-II Cholesterol (free & esters) 5% Intestine&E Phospholipids 3%VLDL TAG 60% (Main lipid)(very low % 10B100, C, E Phospholipids 15%Liver density Cholesterol ( free & esters)15%lipoproteins)IDL Cholesterol (free & esters)(intermediate % 11 45% (Main lipid)Breakdown densityB100, E Phospholipids 25 % of VLDLlipoproteins) TAG 30 % Cholesterol (free & esters) Breakdown LDL 20 %50% (Main lipid)(low densityB100 Phospholipids 22 % of VLDL via lipoproteins) TAG 8 % IDL Cholesterol (free & esters) 15%HDL50 % Phospholipids 30% (Main(high density Liver A,C,D,E lipid) 13 12. LipoproteinFunctionsClinicalsignificanceTransport dietary TAG Increased inChylomicron (mainly), cholesterol &deficiency ofcholesterol esters from thelipoprotein lipase sintestine to the peripheral tissuesTransport endogenous TAG Defect in theirVLDLfrom the liver to the peripheral synthesis leads totissues (Mobilize fat from fatty liver liver)LDL Transport cholesterol from the Their increaseliver to the peripheral tissues leads toatherosclerosis.Remove free cholesterol from Their decreaseperipheral tissues & esterifies leads to 14 HDL 13. 15 14. Uptake of LDL & its regulation The uptake of LDL occurs mainly in the liver(75%), adrenals and adipose tissue. LDL are taken up by cells by LDL receptor-mediated endocytosis. The interaction of LDL with LDL receptorsrequires the presence of apoB100 which is foundonly on LDL). Theendocytosedmembrane vesicles(endosomes) fuse with lysosomes, in which theapoproteins are degraded and the cholesterolesters are hydrolyzed to yield free cholesterol.