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Learning outcomes
 at the end of this lecture , students should be able to:
• 1.Discuss the metabolism of cholesterol and
triglyceride and state the reference interval of each for
apparently healthy subjects.
• 2.Compare and contrast the five lipoprotein classes
based on chemical makeup and clinical significance.
• 3.List the hyperlipoproteinemias and state the
laboratory findings associated with each.
• 4.Discuss hyperlipidemia and its relation to atheroma
and coronary artery disease.
• 5.List the hypolipoproteinemias and state the
laboratory findings associated with each.

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 phospholipids
cholesterol Triglyceride FFA

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 Triglycerides

• A triglyceride: is an ester derived from glycerol and

three fatty acids.

• Fatty acids are saturated or unsaturated.

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 TAG Levels
Normal less than 150 (mg/dL)
Increase in :
1. Cirrhosis or liver damage
2. Diet low in protein and high in carbohydrates
3. Hypothyroidism
4. Nephrotic syndrome
5. Poorly controlled diabetes

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 TAG Levels cont.
Decrease in :
1. Low fat diet
2. Hyperthyroidism
3. Malabsorption syndrome (conditions in which
the small intestine does not absorb fats well)
4. Malnutrition

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 Cholesterol
• Cholesterol is an extremely important
biological molecule that has roles in
membrane structure as well as being a
precursor for the synthesis of the steroid
hormones, bile acids and vitamin D.
• Cholesterol synthesis occurs in the cytoplasm
and microsomes (ER) from acetyl-CoA

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 Cholesterol level
Normal: less than 5mmol/l
Increased with other diseases such as:
• Reduced metabolism due to thyroid problems
• Kidney diseases
• Diabetes particularly when poorly controlled
• Alcohol abuse
• Overweight – this is probably the commonest
cause of high cholesterol levels.
• Smoking, and high blood pressure.
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 Cholesterol level cont.

Decreased levels in:

• Hyperthyroidism
• Liver disease
• Malnutrition
• Cancer
• Chronic infections or inflammation

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 Metabolism TAG & Cholesterol

 TAG is metaboized to glycerol & FFA:

1. in mouth : by lingual lipase
2. in stomach: by heat of stomach important in
emulsification
3. in small intestine: begin in duodenum acted
upon by bile salts & pancreatic lipase

 Cholesterol metabolized to FFA + free

cholestrol by Cholesterol ester enzyme that
hydrolysis ester bound.
 Phospholipids
• A class of lipids that are a major component
of all cells membranes as they canform lipid
bilayers .
• Most phospholipids contain : a diglyceride,
a phosphate group, and a simple organic
molecule such as choline .
• Amphipathic character :
• The 'head' is hydrophilic (attracted to water),
while the hydrophobic 'tails' are repelled by
water and are forced to aggregate.

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Lipoproteins

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 Lipoproteins
lipoprotein is a biochemical assembly that contains •
both protein and lipids.
Core : •
TG, cholesterol ester. •
Surface: •
Phospholipids, free cholesterol, & •
Apo-proteins

Chylomicrons, VLDL & IDL are TG rich. •

LDL & HDL are cholesterol rich •
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Lipoproteins

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Type Source density Size Function
Transport of dietary TAG
CM Intestine (mainly), cholesterol &
cholesterol esters from the
lowest largest
intestine to the tissues.

VLDL Liver low Transport of endogenous TAG

from the liver to the
peripheral tissues

LDL VLDL low transport endogenous fats

and cholesterol to tissues

HDL Liver highest small Transport of cholesterol from

& intestine peripheral tissues to the liver
for elimination
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 Apoprotein
 It is the protein part of lipoproteins.
 It constituting nearly 60% of some HDL and as
little as 1% of chylomicrons.
 Apo CII: activator for lipoprotein lipase.
 Apo AI: activator for Lecithin cholesterol acyl-
transferase (LCAT).
 Apo E:
ligand for chylomicron and VLDL remnant
receptors.
 Apo B100 : ligand for LDL receptors.
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 Reference Of Plasma Lipids
• LDL • HDL
– < 100 →Optimal < 40 → Low
– 160-189→ High ≥ 60 → High
– ≥ 190 → Very High

• Serum Triglycerides
• Total Cholesterol < 150 → normal
– < 200 → normale 200-499 → High
– 200-239 → Borderline ≥ 500 → Very High
– ≥240 → High

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 Laboratory Testing
Electrophoresis :

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ultracentrifugation:

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 Metabolism Of Chylomicrons
1- Chylomicrons synthesized in intestine as nascent
chylomicrons. Main components TAG.
2- Take from HDL (apoCII & apoE) to become
mature chylomicrons.
3- In blood vessels, apoCII activate lipoprotein lipase to
hydrolyze TG to FFA go to tissues & glycerol.
4- Chylomicrons become smaller in size and known as
by chylomicron remnants
5- apoE make receptors of liver identifies chylomicron
remnants to be taken up & metabolized to its
comonents.
Metabolism of chylomicrons
 Metabolism of VLDL
 Synthesized in liver
 Nacsnt VLDL (TAG, apo B100) in live
Take from HDL ( apoCII, apo2424E , chlestrol ester).
 Mature VLDL (apoCII, apoE, cholesterol ester) in blood
vessels.
 In capillaries, apoCII activates lipoprotein lipase to
metabolyze TG to FFA go to tissue & glycerol.
VLDL remnants, (apo B100 ,cholesterol ester) will make
LDL and other part go to liver by apoB100 for compleet
metabolism.
Metabolism of VLDL
 LDL Metabolism

• LDL formed from VLDL metabolism.

 Its main components: cholesterol ester, cholesterol &
apoB100 )
About 25-30% of LDL is taken up by non hepatic
tissues lead to atherosclrosis or familial
hypercholestremia.
The remaining LDL (70-75%) are taken up by the
liver by receptors specific to apoB100 to be
completely metabolized to its different components.
 LDL Metabolism

LDL is removed by
apoB100 receptors
which are mainly
expressed in the liver

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 Metabolism of HDL
Lipoprotein
HDL is secreted in a discoidal
form from the liver and gut.

As it acquires cholesterol from

tissues in the circulation, it
matures into a spherical form
HDL3 through the action of
lecithin:cholesterol acyl
transferase.

Cholesterol and
Atherosclerosis, Grundy)
 Metabolism of HDL (cont.)
• Excess cholesterol is changed to CE by LCAT and
is taken up by HDL3 that is increased in size to
form HDL2.
• HDL2 carries these CE to the liver.
• The cycle is completed by the re-formation
of HDL3, either after selective delivery of
cholesteryl ester to the liver or by hydrolysis
of HDL2 to phospholipids and TG by hepatic
lipase.
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 Metabolism of HDL (cont.)

• Transport of cholesterol from the tissues

to the liver by HDL is known as reverse
cholesterol transport.

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Metabolism of HDL
 Checking lipids
• Nonfasting lipid panel
• measures HDL and total cholesterol
• Fasting lipid panel
• Measures HDL, total cholesterol and TG.
• LDL cholesterol is calculated: LDL cholesterol =
total cholesterol – (HDL + triglycerides/5)
 Dyslipoproteinemias
Definition:
Hyperlipoproteinemias: Presence of raised levels of lipids and/or
lipoproteins in the blood.
Hypolipoproteinemias: Presence of decreased levels of lipids
and/or lipoproteins in the blood.
Common Causes may be:
• Genetic or
• Acquired or secondary.
 1-Hyperlipoproteinemias
• Classified according to the “Fredrickson
Classification”.
• Based on the pattern of lipoproteins on
electrophoresis or ultracentrifugation into 5
types
 Hyperlipoproteinemia Type I
• has a pure elevation of TAG in chylomicrons.
• exists in two forms:
• Type IA(Familial LPL deficiency)
due to deficiency or abnormal form of LPL
• Type Ib (Familial apoCII deficiency)

• Character:
 Increase serum TAG, due to slow clearance of chylomicrons
& VLDL.
 Low level of LDL & HDL.
 Increase serum Chylomicrons.
 No increased risk of coronary heart disease
• Serum appearance: creamy top layer.
 Hyperlipoproteinemia type II
It is the most common. Autosomal dominant defect.

• typeIIA (Familial hypercholesterolemia).

• Cause: Autosomal dominant defect. Defective LDL receptors

or mutation in ligand region of ApoB100.
• Character
 Increase serum LDL.
 Increase serum Cholesterol.
 Atherosclerosis & Coronary disease

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 Hyperlipoproteinemia type II

• The familial form is characterized by: tendon xanthoma,

xanthelasma and premature cardiovascular disease
• Type IIb: Familial Combined Hyperlipo-proteinemia (FCH) or
Secondary combined hyperlipoproteinemia.
 Involve one or multiple genetic defects
high VLDL levels are due to overproduction of substrates,
including TG, acetyl CoA, and an increase in B-100 synthesis
 Hyperlipoproteinemia Type III
Or Familial Dysbetalipoproteinemia
• The most common cause for this form is
mutation in ApoE.
• causing deficiency of chylomicron & IDL
clearance by the liver
• Character
Increase serum IDL (VLDL remnants)
Increased chylomicrons remnants .
Increase serum Cholesterol & TAG
 Hyperlipoproteinemia Type IV
(Familial Hyper-triglycerolemia)

• Autosomal dominant condition due to:

Over production of VLDL or due to mutation in LPL, ApoCII or
Apo B.
• It is commonly associated with type II DM, Coronary artery
disease, obesity, alcohol and progesterone therapy.
• Characters:
 Increase serum TAG.
 Cholesterol levels with the VLDL concentration.
 LDL & HDL tend to be subnormal
 Hyperlipoproteinemia Type V

• It is due to mutation in LPL, ApoCII, Apo B or

Apo E genotypes.
• Character:
Increase serum TAG.
Increase serum chylomicrons & VLDL.
• It is also associated with impaired glucose
intolerance and hyperuricemia.
 Summary Of Hyperlipoproteinemias:
Cause Lipid Lipoprotein Plasma Treat.
appearance

Type I: Ia LPL, TG Chylomicron creamy top Diet control

Ib Apo CII

Type II A Apo B C. LDL Clear hypolipidemic

drugs
Apo B C, TG LDL, VLDL Clear hypolipidemic
B drugs
Type III Apo EII C, TG IDL turbid hypolipidemic
drugs
Type IV Overprod. VLDL TG VLDL turbid hypolipidemic
LPL, drugs
CII,
Apo B
Type V Overprod. VLDL& TG Chylomicron Turbid hypolipidemic
Chylomicron VLDL bottom drugs
LPL, Creamy top
Apo CII,
 Acquired “Secondary” Dyslipoproteinemias

• Diabetes mellitus.
• Use of drugs such as diuretics, beta blockers and
estrogens.
• Hypothyroidism.
• Renal failure.
• Nephrotic syndrome.
• Alcohol.
• Some rare endocrine disorders and metabolic
disorders.
 Hypolipoproteinemias
• Definition: a lack of lipoprotein in the blood
due to genetic or other diseases.
.
Relationship Between Hyperlipidemia & Coronary
Heart Disease

 Relationship:
• The higher the levels of blood LDLs, the higher
the risk for coronary heart disease.
• Conversely, the higher the levels of blood HDLs
in, the lower the risk for coronary heart
disease.

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 Hyperlipdemia and Atheroma
Definition:
 Atheroma is an accumulation of inflammatory cells
(like macrophages), cholesterol, and other lipids in
the inner wall of arteries.
 An atheroma can grow to the point where it
narrows or completely occludes a vessel.
 This can restrict blood, O2, and other nutrients
needed by tissues and organs of the body to
perform important functions in the body.
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 Hyperlipidemia Must be
Remembered as a Controllable
Cause of Coronary Heart Disease,
Especially in The Young