MLAB 2401: Clinical Chemistry Keri Brophy-Martinez Lipids and Lipoproteins Overview Roles of Lipids • Source of energy • Integral part of cellular membranes that assist in cell structure • Converted to hormones or hormone precursors • Insulators for nerve conduction and heat retention Types of Lipids • • • • • Fatty Acids Triglyceride Phospholipids Cholesterol Cholesteryl esters Fatty Acids • Linear chain of C-H bonds • Terminate with a carboxyl group • Integral part of triglycerides/phospholipids • Body makes most fatty acids • Store large amounts of energy • Essential fatty acids: linolenic and linoleic acid – Acquired by diet Triglycerides – Composed of 3 fatty acid molecules, which includes glycerol – Hydrophobic =Water insoluble – Comprises 95% of fat stored in tissue Fatty acids + Glycerol Triglycerides Triglycerides • Exogenous – Come from the diet – Plant or animal sources • Endogenous – Synthesized by the body Phospholipids • Phospholipids – Composed of 2 fatty acid molecules – Amphipathic • Has both hydrophilic and hydrophobic parts – Found on surfaces of lipid layers. – Synthesized in the liver Cholesterol • Cholesterol – Synthesized in animals, plants, our bodies – Functions • Promotes fat absorption in intestine via bile acids • Produces some hormones • Transforms Vitamin D in the skin • Component of cell membranes – Amphipathic Cholesterol • Exogenous – Originates in animal products – Also absorbed via biliary secretions, intestinal secretions, and turnover of intestinal mucosal cells • Endogenous – Produced in the liver and intestine from acetylCoA Cholesterol esters • Hydrophobic • Located in the center of lipoproteins General Structure of Lipoproteins • Size of the molecule correlates with lipid content • Composed of both lipids and proteins • Outer layer of proteins called the apolipoprotein Classification of Lipoproteins Five categories: • Chylomicrons • VLDL • IDL • LDL • HDL Classification of Lipoproteins • Chylomicron – Largest and least dense of the lipoproteins – Lipid-rich transport vessel that carries triglyceride in circulatory system to cells – Observed as a creamy layer in samples • VLDL: very low density lipoproteins – Carry triglycerides to cells for energy use and storage – Liver-made – Specimen appears turbid in fasting samples Classification of Lipoproteins • HDL: High density lipoproteins – Gather excess cholesterol and return them to liver – Made in liver and intestine • LDL: Low-density lipoproteins – Deliver cholesterol to peripheral cells and liver following triglyceride removal Points to Remember: lipoproteins • HDL is helpful – Serves to take cholesterol from the cells • LDL is lethal – Brings cholesterol to the cells Function of Apolipoproteins • Maintain structural integrity • Binding site for cell receptors • Activator/Inhibitor of various enzymes Types of Apolipoproteins • Apo A-I – Major protein on HDL • Apo B – Principal protein on LDL, VLDL and chylomicrons – Two forms: B-100 and B-48 • Apo C – Activates lipoprotein lipase (LPL) to break down triglycerides • Apo E – Promotes binding of LDL, VLDL Lipoprotein Metabolism Pathways LPL: liprotein lipase Physiology and Metabolism • Three pathways • Lipid absorption • Exogenous • Endogenous – Depend on apo-B lipoprotein particles – Transport dietary lipids and hepatic-derived lipids to peripheral cells – Critical transport mechanism of fatty acids to peripheral cells • The fourth pathway – Reverse cholesterol transport – Maintains cholesterol equilibrium Lipid Absorption • During digestion, pancreatic lipase cuts off fatty acids and converts dietary lipids to compounds with amphipathic properties • Triglycerides, phospholipids and cholesterol esters are also transformed to amphipathic lipids • These lipids form aggregates with bile acids in the intestine-called micelles Lipid Absorption- con’t • Absorption occurs when micelles contact membranes of the intestinal mucosal cells • Short chain fatty acids – Enter circulation, picked up by albumin, taken to liver – Long chain fatty acids, monoglycerides, diglycerides • Re-esterified in intestinal cells to form triglycerides and cholestyl esters Exogenous Pathway • Transport of dietary lipids • Chylomicron remnants are taken up by the liver • Once inside the liver, lysosomal enzymes break down the remnants to release fatty acids, free cholesterol and amino acids • Some cholesterol is converted to bile acids • Bile acids and free cholesterol are directly excreted into the bile, but not all exit the body – Half is reabsorbed by the intestine – Remainder found in stool Endogenous Pathway • Transport of hepatic-derived lipids • VLDL loses core lipids once secreted in the circulation • Loss of core lipids leads to conversion of VLDL to remnants • About half of the remnants are converted to LDL, and half are taken in by the liver Reverse Cholesterol Transport Pathway • Mediated by HDL • Excess cholesterol from peripheral cells is transported back to the liver • HDL serves to taxi cholesteryl esters to chylomicrons/VLDL remnants to liver • Conversion of cholesterol into bile acids for removal Population Distribution of Lipids • Concentration differs between men, women and children due to sex hormone concentration and age – Women: • Higher HDL • Lower Cholesterol, triglyceride – Aging • Men and women increase in total cholesterol, LDL cholesterol and triglyceride References • Bishop, M., Fody, E., & Schoeff, l. (2010). Clinical Chemistry: Techniques, principles, Correlations. Baltimore: Wolters Kluwer Lippincott Williams & Wilkins. • http://www.geekymedics.com/bodysystems/metabolism/cholesterol-metabolism/ • http://jimmysmithtraining.com/six-pack-diet/eggs-andcholesterol-whats-the-truth-about-yolks • http://www.healthcentral.com/diet-exercise/h/how-longdoes-it-take-for-polyunsaturated-fatty-acid-to-work.html • http://www.medicine-raw-materials.com/others/page_8.html • Sunheimer, R., & Graves, L. (2010). Clinical Laboratory Chemistry. Upper Saddle River: Pearson .