Overview

Report
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 .

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