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 Endogenous 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 Endogenous 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 acetyl-CoA

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/body-systems/metabolism/cholesterol-metabolism/ http://jimmysmithtraining.com/six-pack-diet/eggs-and-cholesterol-whats-the-truth-about-yolks http://www.healthcentral.com/diet-exercise/h/how-long-does-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 .