MLAB 2401: Clinical Chemistry Keri Brophy-Martinez Lipids and Lipoproteins Overview.

MLAB 2401: Clinical ChemistryKeri Brophy-Martinez

Lipids and LipoproteinsOverview

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 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 .