LIPIDS AND LIPOPROTEINS Dr. Gamal Gabr

Lecture Outline What are lipoproteins? What do they do? Basic structure of lipoproteins Hyperlipoproteinemia Role of lipoproteins in atherosclerosis

What are lipoproteins and why do we need them? Lipoproteins are a handful of different molecules that interact with water insoluble fat molecules, and transports those fats in the plasma Different lipoproteins are responsible for the transportation of different fats Lipoproteins allow fat to be dissolved into the plasma

What are lipoproteins? Molecular complexes that consist of lipids and proteins. They function as transport vehicles for lipids in blood plasma. Lipoproteins deliver the lipid components (cholesterol and triglyceride etc.) to various tissues for utilization. Inner droplet of neutral (water-insoluble core lipids); primarily triglycerides and cholesteryl esters A solubilizing surface layer of phospholipids and unesterified cholesterol Specific proteins (apolipoproteins) attached to the outer lipid layer through their specific lipophilic domains

There are 4 types of lipoproteins Chylomicrons Transport of dietary triglycerides from the GI tract to the liver Very Low Density Lipoproteins ( VLDL ) Transport of triglycerides from the liver to tissues for storage and energy Low Density Lipoproteins ( LDL ) Transports cholesterol to peripheral tissues High Density Lipoproteins ( HDL ) Transports cholesterol away from the peripheral tissues to the liver

Triglycerides Glycerol with 3 attached fatty acids Exogenesis source : Dietary Endogeneous : Liver and tissue storage 95 % of body fat is triglycerides Energy source when plasma glucose is decreased Triglyceride catabolism is regulated by lipase, epinephrine and cortisol Triglycerides transported by Chylomicrons ( exogeneous ) and VLDL ( endogenous )

Transported by HDL and LDL Cholesterol Found only in animals Important component of membranes, steroid hormones, bile and Vitamin D Exogeneous cholesterol comes from diet Endogeneous cholesterol is synthesized by the liver 70 % of cholesterol associated with cellular components 30 % is in the plasma ( ⅓ free form , ⅔ esterfied ) Transported by HDL and LDL

Phospholipids Important components of cell membranes Lecithin and sphingomyelin are utilized to determine fetal lung maturity from amniotic fluid ( L / S Ratio ) Glycolipids Lipids with a carbohydrate component ABO antigen are glycolipids

Structure of lipoprotein Hydrophobic lipids (TG, CE) in the core Amphiphilic lipids (C, PL) and proteins on the surface

Classification of plasma lipoproteins according to their density Chylomicron (CM) Very low density lipoprotein (VLDL) Intermediate density lipoprotein (IDL) Low density lipoprotein (LDL) High density lipoprotein (HDL)

Apoliproproteins Outer protein “shell” of the lipoprotein molecule The protein – lipid interaction allows the water insoluble lipid to become soluble in plasma The apolipoprotein is responsible for the interactions with cell membranes and enzymes to transport lipids to specific locations Lipoproteins Classified according to density and electrophoresis migration Lipoproteins differ in their sizes, weights, chemical composition and artherogenicity ( association with heart disease ) There are four main types of lipoproteins CHYLOMICRONS VLDL LDL HDL

Chylomicrons Transports exogeneous ( dietary ) triglycerides 90 - 95 % by weight is triglycerides Absent from fasting plasma Removed from the plasma within 6 hours by the liver Inadequate clearance produces a creamy layer on the plasma VLDL ( Very Low Density Lipoproteins ) Transports endogeneous triglycerides from liver to tissues 50 - 65 % by weight is triglycerides Excess dietary carbohydrates are converted to triglycerides by the liver LDL ( Low Density Lipoproteins ) Transports cholesterol from liver to the tissues Synthesized in the liver Approximately 50 % by weight cholesterol Most atherogenic lipoprotein … “ Bad Cholesterol “

HDL ( High Density Lipoprotein ) Transports excess cholesterol from the tissues back to the liver ( reverse transport ) Synthesized in the liver and intestines Composition 30% PHOSPHOLIPIDS 20% CHOLESTEROL 50% APOPROTEIN The “good “ cholesterol

Characteristics of human plasma lipoproteins CM VLDL LDL HDL Density (g/mL) <0.96 0.96-1.006 1.006-1.063 1.063-1.21 Diameter (nm) 100-1000 30-90 20-25 10-20 Apolipoprotein A,C,E,B48 A,C,E,B100 B100 A,C,D,E Composition (%) Proteins 2 10 20 40 Lipids 98 90 80 60 Lipid composition (%) TG 88 55 12 12 CE+C 4 24 59 40 PL 8 20 28 47 Free fatty acid - 1 1 1

Lipoprotein physiology and metabolism Water insoluble lipids are digested unto more water soluble ( polar ) compounds in the GI tract Triglycerides are digested into fatty acids Cholesterol – esters are converted into free cholesterol Fatty acids are converted into triglycerides by the liver anf adipose tissues ( fat ) Most cholesterol synthesis occurs in the liver - Most cholesterol lowering drugs target this synthesis Cholesterol is a main component of bile ( needed for dietary absorption of fat )

Exogeneous Pathway Transport of dietary lipids, mostly the chylomicrons transportation of triglycerides to the liver Endogeneous Pathway Transportation of lipids from the liver to the tissues ( VLDL & LDL )

Effects of hormones Insulin Remember, insulin always decreases plasma glucose Inactivates lipase … decreases lipolysis and the catabolism of triglycerides to fatty acids / glucose Stimulates lipogenesis ( fatty acid conversion to triglycerides ) Insulin helps make fat In diabetes mellitus, insulin deficiency promotes the release of fatty acids and their conversion to triglycerides by the liver

Apolipoproteins Act as structural components of lipoproteins Recognize the lipoprotein receptors on cell membrane surface as ligand Activate/inhibit enzymes involved in lipoprotein metabolism

Apo AI: Activator LCAT Apo AII: Inhibitor of hepatic lipase (HL) Apo A-IV: Activator of LCAT Apo B-100 (liver, 4564 Aa): structure, ligand Apo B-48 (intestine, 2152Aa): structure Apo C-I : Activator of LCAT Apo C-II: Activator of LPL Apo C-III: Inhibitor of LPL Apo D: Function unknown Apo E: Ligand

What do lipoproteins do? Serve to transport lipids and lipid-soluble compounds between tissues and organs Substrates for energy metabolism (TG) Essential components for cells (PL, C) Precursors for hormones (C) Lipid soluble vitamins Precursors for bile acids (C)

Lipoprotein Top 10 Lipoproteins transport various lipids ( fats ) thru plasma to different locations High relationship between specific lipoproteins and CAD Apolioproteins are the protein “shells” that interact with lipids and allow them to be water soluble HDL ( Good Cholesterol ) transports cholesterol away from tissues to the liver LDL ( Bad Cholesterol ) transports cholesterol to the tissues from the liver VLDL transports endogenous triglycerides from liver to tissues Chylomicrons transport exogenous triglycerides from GI tract to liver