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Cholesterol biosynthesis, regulation and important compounds
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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