cholesterol metabolism

1. Prof. Dr.
Essam Hammouda

2. Cholesterol Metabolism II
• OBJECTIVES:
I - Transport of cholesterol.
II - Normal plasma cholesterol levels.
III - Hypercholesterolemia (definition and causes).
IV - Hypercholesterolemia and cardiovascular
diseases and Hypocholesterolemia.
V - Excretion.

3. I. Transport of cholesterol:
A. Cholesterol is hydrophobic. It travels through
the blood attached to a protein. The combination
protein and cholesterol is called Lipoprotein. It is
transported in plasma in the more soluble
lipoprotein forms: LDL, VLDL and HDL (see
plasma lipoproteins).

4. B. Free cholesterol is removed from tissues by
HDL and transported to be excreted by the liver.
HDL removes cholesterol from arteries and
plaques and transport it to the liver, so it slows
atherosclerosis.
C. Cholesterol ester is the storage form of
cholesterol, It is formed in both tissues and
plasma.

5. 1. In tissues (liver),
cholesterol is esterified by ACAT enzyme
(acyl CoA cholesterol acyl transferase):
Cholesterol + Acyl CoA  Cholesteryl ester + CoASH
2. In plasma,
cholesterol is esterified by LCAT enzyme
(Lecithin cholesterol acyl transferase).
LCAT is associated with HDL.
Cholesterol + lecithin  Cholesteryl ester+ lysolecithin

9. II. Normal Plasma cholesterol levels:
 Cholesterol present in plasma is either free or
esterified (cholesteryl ester).
1. Total plasma cholesterol: 140 -220 mg/dl.
2. Free plasma cholesterol: 26 - 126 mg/dl.
 The body needs only a limited amount of
cholesterol. When there is too much, health
problems such as heart disease may develop.

10. III. Hypercholesterolemia:
1. Definition: It is increased plasma cholesterol
concentration above 220 mg/dl.
Hypercholesterolemia is a major risk factor for
heart diseases.
2. Causes:
a) Diet rich in carbohydrate, cholesterol and
saturated fatty acids.
b) Hypothyroidism as thyroxin stimulates
conversion of cholesterol to bile acids.
c) Diabetes mellitus.

11. d) Kidney affection (nephrotic syndrome).
e) Obesity.
f) Obstructive jaundice due to decreased
excretion of cholesterol and bile acids.
g) Familial hypercholesterolemia.

16. Hypocholesterolemia:
1. Definition: It is decreased plasma cholesterol
concentration below 140 mg/dl.
2. Causes :
a) Prolonged fasting which causes decreased secretion
of Insulin (decreased activation of HMG-CoA
reductase).
b) Diet rich in unsaturated fatty acids and poor in
saturated fatty acids, carbohydrate and cholesterol.
c) Liver diseases, as liver is the site where most plasma
cholesterol is synthesized.
d) Hyperthyroidism.
e) Chronic Infection as tuberculosis.

17. V. Excretion of cholesterol:
About one gram of cholesterol is excreted daily. It is
secreted as cholesterol, bile acids and coprostanol:
A. 1/2 Gram cholesterol is excreted as such with bile,
which transports it to the intestine for elimination.
B. 1/2 Gram cholesterol is converted to bile acids,
which is excreted in the feces.
C. Some cholesterol is synthesized by intestinal cells
and modified by bacteria before excretion. Bacterial
enzymes reduce cholesterol into coprostanol, which is
excreted into feces.

19. The linking factor: insulin resistance when cells no
longer respond appropriately to the hormone insulin.
As a result, a person may develop an abnormal
cholesterol profile—low high-density lipoprotein (HDL,
or "good cholesterol"), high low-density lipoprotein
(LDL, or "bad cholesterol"), and high triglycerides.
These cholesterol abnormalities then increase a
person's risk for heart disease and stroke.

20. Insulin Resistance and Cholesterol Changes
After eating a meal, carbohydrates are broken down into
glucose by your digestive system. This glucose is then
absorbed through the wall of your intestines into your
bloodstream.
Once there, insulin brings glucose into various cells, so
they have the energy to function and do their jobs. Insulin
also blocks the breakdown of fat into fatty acids (lipolysis)
within your body.

21. Insulin resistance is when the cells become less responsive
to this process. As a result, blood sugar eventually
increases, which is why it's considered a precursor to pre-
diabetes and type 2 diabetes.
Fats are also broken down within the body at an increased
rate, and this ultimately leads to various cholesterol
changes. Specifically, insulin resistance lowers HDL and
raises triglycerides and LDL.
A low HDL level or a high LDL level paired with a high
triglyceride level is linked to the buildup of plaque (fatty
deposits) in the walls of arteries. This condition is
called atherosclerosis and it increases your risk of
developing a heart attack and stroke.