1. MLAB 2401: Clinical Chemistry Keri 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 Endogenous 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 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

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
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

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.
Sunheimer, R., & Graves, L. (2010). Clinical Laboratory Chemistry. Upper Saddle River: Pearson .