Lipids and Lipoproteins

Question 1

What is a lipid

Answer 1

A lipid is a fatty, oily, or wax-like compound that is insoluble in water (hydrophobic). It is a combination of glycerol and fatty acids. When mixed in a watery solution, lipids disperse into tiny droplets to produce an emulsion.

Serve as the precursor to compounds like hormones, prostaglandins, leukotrienes, and lipoxins

Question 2

Roles of lipids in biology

Answer 2

Storage of excess energy

Important part of cell membranes due to physical properties

Question 3

Fatty Acids

Answer 3

Linear chains of C–H bonds that terminate with a carboxyl group (–COOH)

The Carbon can be double bonded to another carbon molecule to form un saturated fatty acids

Monounsaturated fatty acids - have one carbon double bond
Polyunsaturated fatty acids - have 2 or more carbon double bonds

These double bonds give lipids their unique physical properties

Question 4

Majority of plasma fatty acids are instead found as a constituent of ____________

Answer 4

Triglycerides or phospholipids

Question 5

Most fatty acids are synthesized in the body from carbohydrate precursors, except ______ & ______ acids, which are referred to as essential fatty acids

Answer 5

Linoleic and linolenic acids

Question 6

Trans fatty acids

Answer 6

Trans fatty acids are unsaturated fatty acids that go through the hydrogenation process.

Results in margarines and manufactured cooking oils.

Excessive consumption is associated with elevated LDL, decreased HDL, and increased risk for congenital heart disease (CHD)

Question 7

Triglycerides Info

Answer 7

Contain three fatty acid molecules attached to one molecule of glycerol by ester bonds in one of three stereochemically distinct bonding positions

From plant sources, such as corn, sunflower seeds, and safflower seeds, are rich in polyunsaturated fatty acids and are oils at room temperature

Triglycerides from animal sources contain mostly saturated fatty acids and are usually solid at room temperature.

Hydrophobic, making it water insoluble

Uncharged molecule so it is a neutral lipid

Question 8

Phospholipids info

Answer 8

Similar in structure to triglycerides except that they only have two esterified fatty acids

Has a hydrophilic phospholipid head group instead of 3rd fatty acid

Because they contain both hydrophobic fatty acid C–H chains and a hydrophilic head group, they are by definition amphipathic lipid molecules and, as such, are found on the surface of lipid layers or on the surface of lipoprotein particle.

Question 9

Cholesterol

Answer 9

Also an amphipathic lipid and is found on the surface of lipid layers along with phospholipids

Can also exist in an esterified form called cholesteryl ester, with the hydroxyl group conjugated by an ester bond to a fatty acid

Almost exclusively synthesized by animals, but plants do contain other sterols (called phytosterols) similar in structure to cholesterol

Does not serve as fuel source unlike other lipids

Function is being converted to bile acids for fat absorption, conversion to vitamin D3, and conversion to steroid horomones

Question 10

Chylomicrons

Answer 10

Rich in triglycerides

The largest and the least dense of the lipoprotein particles

Turbidity or milky appearance of postprandial plasma specimens

Principal role of chylomicrons is the delivery of dietary lipids to hepatic and peripheral cells

Question 11

Very-Low-Density Lipoprotein

Answer 11

Produced primarily by the liver and like chylomicrons, they are also rich in triglycerides

Like chylomicrons, they also reflect light and account for most of the turbidity observed in fasting hyperlipidemic plasma specimens, although they do not form a creamy top layer like chylomicrons

Carry endogenous triglycerides from the liver to peripheral tissue, mostly during fasting, for energy utilization/storage

Question 12

Intermediate-Density Lipoproteins

Answer 12

Also referred to as VLDL remnants, normally only exist transiently during the conversion of VLDL to LDL

IDLs are not typically present in high quantities in normal plasma due to conversion during overnight fast

In patients with hyperlipoproteinemia type III, elevated levels of IDLs can be found in plasma.

Question 13

Low-Density Lipoproteins

Answer 13

Primarily contains apo B100 and is more cholesterol rich than other apo b–containing lipoproteins

Can exist in various sizes and compositions and have been separated into as many as eight subclasses through density ultracentrifugation or gradient gel electrophoresis

LDL particles have been shown to be more proatherogenic and may be a better marker for CHD risk.

Question 14

Lipoprotein (a)

Answer 14

Are heterogeneous in both size and density as a result of a differing number of repeating peptide sequences, called kringles, in the Apo(a) portion of the molecule

Clinical studies have demonstrated increased risk of both myocardial infarction and stroke with increasing Lp(a) concentration.
- The measurement of Lp(a) is often underutilized in clinical practice

Question 15

High-Density Lipoproteins

Answer 15

Smallest and most dense lipoprotein particle, is synthesized by both the liver and the intestine

Ability of HDL to remove cholesterol from cells, called reverse cholesterol transport, referred to as good cholesterol

Question 16

Lipoprotein X

Answer 16

Abnormal lipoprotein only produced in patients with cholestatic liver disease or in patients with mutations or deficiencies of lecithin–cholesterol acyltransferase (LCAT)

Is mainly removed by the reticuloendothelial system of the liver and the spleen

Question 17

Lipoprotein Physiology & Metabolism …. Pathways

Answer 17

4 major pathways involved in lipoprotein metabolism

3 of the 4 (lipid absorption pathway, exogenous pathway, and endogenous pathway) depend on Apo B containing lipoproteins

The cholesterol transport pathway is responsible for maintain cholesterol equilibrium

Question 18

Lipid Absorption

Answer 18

During the process of digestion, pancreatic lipase first converts dietary lipids into more polar compounds with amphipathic properties by cleaving off fatty acids.

 - Triglycerides are transformed into monoglycerides and diglycerides.

 - Cholesterol esters are transformed into free cholesterol.

 - Phospholipids are transformed into lysophospholipids.

Question 19

Exogenous Pathway

Answer 19

New synthesized chylomicrons are initially secreted into the lac-teals (small intestine lymphatic vessels) and then pass into the lymphatic ducts, eventually entering the circulation by way of the thoracic duct

A key protein in triglyceride metabolism is Apo C2

Once in the liver, lysosomal enzymes break down the remnant particles to release free fatty acids, free cholesterol, and amino acids.

Question 20

Endogenous Pathway

Answer 20

Most triglycerides that are packaged into VLDL are derived from the diet after recirculation from adipose tissue.

IDL is taken up by the liver via Apo E and the LDL receptor, and the triglycerides in IDL are removed by hepatic triglyceride lipase, located on hepatic endothelial cells, ultimately producing LDL.

Abnormalities in LDL receptor function result in elevation of LDL in the circulation and lead to hypercholesterolemia and premature atherosclerosis.

Question 21

Reverse Cholesterol Transport Pathway

Answer 21

One of the major roles of HDL is to maintain the equilibrium of cholesterol in peripheral cells by the reverse cholesterol transport pathway.
- Believed to remove excess cholesterol from cells by multiple pathways
- In the aqueous diffusion pathway acts as a sink

Another pathway in which HDL mediates the removal of cholesterol from cells involves the ABCA1 transporter.
- A member of the ATP-binding cassette transporter family, which pumps various ligands across the plasma membrane
- Defects in the gene for the ABCA1 transporter lead to Tangier disease, a disorder associated with low HDL and a predisposition to pre-mature CHD.

Question 22

Lipid and Lipoprotein Population Distributions

Answer 22

Men and women both show a tendency toward increased total cholesterol, LDL-C, and triglyceride concentrations with increased age.

Incidence of heart disease is strongly associated with serum cholesterol concentration, particularly LDL-C.

Question 23

National Cholesterol Education Program

Answer 23

It is recommended that all adults (20 years and older) have a fasting lipo-protein profile performed (total cholesterol, LDL-C, and HDL-C and triglycerides) once every 5 years.

Question 24

Dyslipidemia and Children

Answer 24

Data collected between 1998 and 2010 estimated that 24.6% of US children aged 9 to 11 had either abnormally low HDL cholesterol or elevated non-HDL cholesterol.

Question 25

Total cholesterol levels

Answer 25

Youth….
Acceptable = < 170
Borderline = 170 - 199
High = > 200

Adults…..
Acceptable = > 190
Borderline = 190 - 225
High = > 200

Should be less than 200 mg/dL

Question 26

Low Density Lipoprotein levels

Answer 26

Youth….
Acceptable = < 110
Borderline = 110 - 129
High = > 130

Adults…..
Acceptable = < 120
Borderline = 120 - 160
High = > 130

Question 27

Non-High Density Lipoprotein levels

Answer 27

Youth….
Acceptable = < 120
Borderline = 120 - 144
High = > 145

Adults…..
Acceptable = < 150
Borderline = 150 - 190
High = > 145

Question 28

Triglyceride levels

Answer 28

0-9 years…..
Acceptable = < 75
Borderline = 75 - 99
High = > 100

10-19 years……
Acceptable = < 90
Borderline = 90 - 129
High = > 130

Question 29

High Density Lipoprotein levels

Answer 29

Youth….
Acceptable = > 45
Borderline = 45 - 40
*Low = < 40

Adults…..
Acceptable = > 45
Borderline = 45 - 40
*Low = < 40

Question 30

Arteriosclerosis

Answer 30

Relationship between heart disease and dyslipidemias (high levels of lipids in the blood) stems from the deposition of lipids, mainly in the form of esterified cholesterol.

Plaque formation involves repeated cycles of cell injury, followed by infiltration and cell proliferation to repair the site. LDL is believed to play a central role in initiating and promoting plaque formation.

Measurement of total cholesterol, HDL-C, LDL-C, and triglyceride levels is key.

Question 31

Hyper/Hypo-lipoproteinemia

Answer 31

Caused by malfunctions in synthesis, transport, or catabolism of lipoproteins

Dyslipidemias can be subdivided into two major categories:
1. Hyperlipoproteinemia
2. Hypolipoproteinemia

Question 32

Hyperlipoproteinemia

Answer 32

Are diseases associated with elevated lipoprotein levels

Question 33

Hypolipoproteinemia

Answer 33

Are diseases associated with decreased lipoprotein levels.

Question 34

Hypercholesterolemia

Answer 34

Studies continue to show a strong correlation with hypercholesterolemia and coronary heart disease mortality.

Associated with genetic abnormalities that predispose affected individuals to elevated cholesterol levels, is called familial hypercholesterolemia (FH).

Question 35

Hypertriglyceridemia

Answer 35

Borderline high triglycerides as levels of 150 to 200 mg/dL.

Very high triglycerides are levels greater than 500 mg/dL.

Severe would be levels triglyceride levels of >880 mg/dL associated with recurrent/acute pancretitis.

Are influenced by hormones like insulin, pituitary growth hormone, adrenocorticotropic hormone (ACTH), etc…

Treatment of hypertriglyceridemia consists of dietary modifications, fish oil, and/or triglyceride-lowering drugs.

Question 36

Combined Hyperlipidemia

Answer 36

Generally defined as the presence of elevated levels of serum total cholesterol and triglycerides

Question 37

Lp(a) Elevation

Answer 37

Elevations in the serum concentration of Lp(a), especially in conjunction with elevations of LDL, increase the risk of CHD and CVD.

Question 38

Non-HDL Cholesterol Elevation

Answer 38

Recent studies have shown that elevated levels of non-HDL-C are associated with increased CVD risk, even if the LDL-C levels are normal.

Question 39

Cholesterol Measurement

Answer 39

Prefer 12 hour fasting sample, stable for several days refrigerated

First part of the lipid panel

Reference method is Gas Chromatography-Mass Spectrometry

Enzyme cholesteryl ester hydrolase reaction sequence is most commonly used to measure cholesterol.

Measured at 500 nm

Vitamin C and bilirubin are reducing agents that interfere with this reaction

Question 40

Triglyceride Measurement

Answer 40

Used in the estimation of LDL-C

Endogenous free glycerol interferes and about 20% of samples have higher glycerol levels

Current reference method is Gas Chromatography-Mass Spectrometry

Question 41

HDL Methods

Answer 41

For many years was separated almost exclusively by chemical precipitation, involving a two-step procedure with manual pretreatment

Been replaced with the development of anew class of direct, sometimes termed homogeneous, methods, which automate the HDL quantification

    - Have been shown to lack specificity for HDL in unusual specimens like patients with kidney/liver conditions

Question 42

LDL Methods

Answer 42

Research method for LDL-C quantitation and the basis for the reference method has been designated β-quantification. Requires ultracentrifugation.

A common approach is using the Friedewald calculation.
- HDL-C is quantified either after precipitation or using one of the direct methods, and total cholesterol and triglycerides are measured in the serum.

LDL-C = Total CHOL – HDL – Trig/5

Question 43

Lipid Panel Sample

Answer 43

Primarily done on fasting samples

Serum is sample of choice

EDTA plasma used to be sample of choice
- Microclots and EDTA dilution were disadvantages
- Use of this sample requires a correction factor of 1.03