Cholesterol metabolism

CHOLESTEROL METABOLISM

Dr. Vijay Marakala, MBBS, MD.

Senior LecturerBIOCHEMISTRY

IMS, MSU.

CHOLESTEROLNo vegetable oil contains any

cholesterol.

Cholesterol is the major sterol in animal tissues.

Only a little portion of the body cholesterol is derived from diet.

The bulk of it is synthesized in the body.

CHOLESTEROL

FUNCTIONS OF CHOLESTEROL

CHOLESTEROL BIOSYNTHESIS

•All the carbon atoms of cholesterol are derived from acetyl CoA

•Liver and Intestine are major sites of cholesterol

STEPS OF DE NOVO CHOLESTEROL SYNTHESIS

•Step 1—Biosynthesis of Mevalonate

•Step 2—Formation of Isoprenoid Units

•Step 3—Six Isoprenoid Units Form

Squalene

•Step 4—Formation of Lanosterol

•Step 5—Formation of Cholesterol

2 Acetyl-CoA

Acetoacetyl-CoA

HMG-CoA

Mevalonate Several steps

3 Acetyl-CoA

HMG-CoA

Mevalonate

Isopentenyl pyrophosphate X6

Squalene

Lanosterol

Cholesterol

C6

C5

C30

C30

C27

Regulation of de novo synthesis of cholesterol

HMG-CoA reductase

Feedback regulation

Hormonal regulation

Nutritional regulation

HMG-CoA reductase (active)

HMG-CoA reductase (Inactive)

Acetyl-CoA

HMG-CoA

Mevalonate

CHOLESTEROL

Insulin

Glucagon

Increased caloric intake, Thyroid hormone

Bile acids, glucocorticoids, Dietary cholesterol

P

Dephosphorylation

Phosphorylation

+

+

+

-

Competitive inhibitor drugs of HMG-CoA REDUCTASE

PARVASTATIN

LOVASTATIN

MEVASTATIN

SIMVASTATIN

FLUVASTATIN

IMPORTANT COMPUNDS SYNTHESIZED FROM CHOLESTEROL

CHOLESTEROL-BIOLOGICAL IMPORTANT COMPONDS

CHOLESTEROL

BILE ACIDS

STEROID HORMONESVITAMIN D

FORMATION OF BILE ACIDS

• Bile acids are synthesized in the liver from cholesterol.• They contain 24 carbon atoms

Cholic acid

Chenodeoxycholic acid

Cholesterol

7-α- hydroxyl cholesterol

Bile acids

Vitamin C

O2

H2O

7-α- hydroxylase

FORMATION OF STEROID HORMONES

Cholesterol

Progesterone

Androgens

Estrogens

Glucocorticoids Mineralocorticoids

Cholesterol

7-dehydrocholesterol

CHOLECALCIFEROL[Vitamin D3]

UV light

Dehydrogenase

FORMATION OF VITAMIN D

BLOOD CHOLESTEROL

Free cholesterol about 30%

Ester form(cholesterol

ester) is about 70%Blood levels are influenced by

both genetic and environmental factors

EXCRETION OF CHOLESTREROL

•Cholesterol is excreted in faeces

•Cannot be destroyed by oxidation to CO2 and H2O, because of absence of enzyme capable of catabolising the steroid nucleus

•About 1gm of cholesterol is eliminated from the body per day

DISORDER OF CHOLESTEROL METABOLISM

FAMILIAL HYPERCHOLESTEROLAEMI

A

Deficiency or malfunction of LDL

receptors

Plasma LDL & cholesterol level are

elevated

ATHEROSCLEROSIS

Deposition of cholesterol and other lipids in the arterial

wall

Leads to formation of plaque→endothelial

damage→IHD