mlab 2401: clinical chemistry keri brophy-martinez lipids and lipoproteins overview
TRANSCRIPT
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
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 acetyl-CoA
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• 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
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 .