METABOLISM OF

CHOLESTEROL
Introduction

 Most important animal steroid

 Amphipathic in nature
 Light yellow crystalline solid
 Cholesterol content : 2 gm/kg body weight so, 140 gm in
70 kg man.
 Function

 It is a structural component of cell membrane .

 Cholesterol is a pre cursor for the synthesis of all other steroids in
the body, these includes steroids hormones , vitamin D ,and bile
acids.
 Cholesteryl esters are formed of fatty acids i.e transported to liver
for oxidation.
 BIOSYNTHESIS OF CHOLESTEROL

 About 1 gm of cholesterol is synthesized per day in adults .

 The major sites of synthesis of cholesterol are liver , adrenal cortex ,
testis , ovaries and intestine.
 Liver synthesizes : 50% of total cholesterol - largest contribution
 Intestine synthesizes : 15% of total cholesterol
 All nucleated cells can synthesizes cholesterol including arterial .
 Acetate of acetyl CoA provides all the carbon atoms in
cholesterol .
 The reducing equivalents are supplied by NADPH while ATP
provides energy.
 SYNTHESIS OF CHOLESTEROL

 It includes 5 stages :
1. Synthesis of HMG CoA
2. Formation of mevalonate (6C)
3. Production of isoprenoid units (5C)
4. Synthesis of squalene (30C)
5. Conversion of squalene to cholesterol (27C)
1. SYNTHESIS OF HMG CoA
2) Formation of mevalonate
3) Production of isoprenoid units
4) Synthesis of squalene
 5) Conversion of squalene to
cholesterol

Squalene undergoes hydroxylation and

cyclization utilizing o2 and NADPH and
gets converted to Lanosterol. The
formation of cholesterol form lanosterol is
a multi step process with a series of
about 19 enzymatic reaction.

Those enzymes are associated with

endoplasmic reticulum.
 Regulation of cholesterol synthesis

 Cholesterol bio synthesis is control by the rate limiting enzyme

HMG CoA reductase which is found in association with ER and is
subjected to different metabolic controls.
 1) Feedback Control
 Regulatory enzyme : HMG CoA reductase
 Transcription of enzyme is inversely proportional to concentration
of cholesterol
Regulation of cholesterol synthesis

 2) Hormonal Regulation
 Insulin and Thyroxin increases the activity of HMG CoA reductase.
 Glucagon and glucocorticoids decreases its activity.
 Excretion of cholesterol

 The steroid nucleus (ring structure) of cholesterol can’t be

metabolized in human body. Cholesterol (50%) is converted to bile
acids , excreted in feces .
 The unabsorbed portion is acted upon by intestinal bacteria to
form cholestanol and coprostanol which are excreted as fecal
sterols.
 Liver is the only organ that can excrete cholesterol through bile .
 Clinical significance of cholesterol

 Hypercholesterolemia
Increase in plasma cholesterol concentration (> 200mg/dl)
more common
1. Atherosclerosis – myocardial infarction
2. Diabetes mellitus
3. Hypothyroidism
4. Obstructive jaundice
5. Nephrotic syndrome
Hypocholesterolemia

• Decrease in plasma cholesterol (< 140 mg/dl)

• less common
1. Hyperthyroidism
2. Pernicious anemia
3. Malabsorption syndrome
4. Hemolytic jaundice
Reference

 Biochemistry , Satyanarayan
 Biochemistry , Harper