MLAB 2401: Clinical Chemistry Keri Brophy-Martinez

1. MLAB 2401: Clinical ChemistryKeri Brophy-Martinez Lipids and Lipoproteins Overview

2. 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

3. Types of Lipids • Fatty Acids • Triglyceride • Phospholipids • Cholesterol • Cholesteryl esters

4. 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

5. Triglycerides • Composed of 3 fatty acid molecules, which includes glycerol • Hydrophobic =Water insoluble • Comprises 95% of fat stored in tissue Fatty acids + Glycerol Triglycerides

6. Triglycerides • Exogenous • Come from the diet • Plant or animal sources • Endogenous • Synthesized by the body

7. 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

8. 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

9. 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 acetyl-CoA

10. Cholesterol esters • Hydrophobic • Located in the center of lipoproteins

11. 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

12. Classification of Lipoproteins • Five categories: • Chylomicrons • VLDL • IDL • LDL • HDL

13. 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

14. 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

15. Points to Remember: lipoproteins • HDL is helpful • Serves to take cholesterol from the cells • LDL is lethal • Brings cholesterol to the cells

16. Function of Apolipoproteins • Maintain structural integrity • Binding site for cell receptors • Activator/Inhibitor of various enzymes

17. 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

18. Lipoprotein Metabolism Pathways LPL: liprotein lipase

19. 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

20. 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

21. 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

22. Exogenous Pathway • Transport of dietary lipids • Chylomicronremnants 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

24. 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

26. 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

27. 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

28. 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 .