This document discusses cholesterol, including that it is a major sterol in animal tissues, is both obtained through diet and synthesized in the body, and serves various structural and metabolic functions. It describes cholesterol biosynthesis occurring primarily in the liver, intestine, and other tissues, requiring acetyl-CoA, ATP, and NADPH. The rate-limiting enzyme HMG-CoA reductase is regulated by feedback and hormones. Factors like genetics, diet, lifestyle, and drugs can affect serum cholesterol levels. Disorders like familial hypercholesterolemia involve inherited defects in lipid metabolism and LDL receptors, elevating LDL and total cholesterol and increasing atherosclerosis risk.

2. CHOLESTEROL
No vegetable oil contains any cholesterol
Cholesterol is the major sterol in animal tissues
Total cholesterol in a 70 kg man: 140 gm (2gm/kg)
A portion of the body cholesterol is derived from diet (egg yolk,
meat, liver brain)
A little more than half of it is synthesized in the body (700 mg/d)

3. Structural component of cell membrane
Steroid hormone (Progesterone, estrogens, glucocorticoid,
mineralocorticoids)
Vitamin D (from 7-dehydrocholesterol)
Bile acids (Cholic acid, Chenodeoxycholic acid)
Transport of fatty acid to liver as cholesteryl esters (plasma
lipoproteins)

5. CHOLESTEROL BIOSYNTHESIS
• Virtually all tissues containing nucleated cells are capable
• Occurs in ER and cytosol
• Site: Liver (10%), Intestine (10%), Adrenal cortex,
Reproductive tissues, Skin
• All the carbon atoms of cholesterol are derived from acetyl
CoA
• Requirements: Acetyl CoA- 18 moles
ATP- 36 moles
NADPH- 16 moles

6. STEPS OF DE NOVO CHOLESTEROL SYNTHESIS
• Step 1—Biosynthesis of Mevalonate (6C)
• Step 2—Formation of Isoprenoid Units (5C)
• Step 3—Six Isoprenoid Units Form Squalene (30C)
• Step 4—Formation of Lanosterol (30C)
• Step 5—Formation of Cholesterol (27C)

7. Acetoacetyl-CoA
HMG-CoA
Several steps
Cholesterol
• First 2 steps are similar
as ketone body synthesis
• But KB synthesis occurs
in mitochondria

8. HMG-COA REDUCTASE
 Rate limiting enzyme
 Present in endoplasmic reticulum
Regulated by-
• Feedback control (mevalonate, cholesterol)
• Hormonal regulation Insulin, thyroxin (+)
• Drugs (Statins) Glucagon, glucocorticoid (-)
• Bile acids, fasting

9. 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
+
+
+
-
REGULATION
OF
DE
NOVO
SYNTHESIS
OF
CHOLESTEROL

10. EXCRETION OF CHOLESTEROL
• Cannot be destroyed by oxidation to CO2 and H2O,
because of absence of enzyme capable of catabolising the
steroid nucleus
• 50% is converted to bile acid
• Cholesterol is excreted in faeces
• About 1gm of cholesterol is eliminated from the body
per day (C-0.6g/d; bile acid-0.4 g/d)

11. BLOOD CHOLESTEROL
Plasma cholesterol is associated with different lipoprotein fraction (LDL, HDL, VLDL)
Free cholesterol -30%; Ester with long chain FA as cholesteryl ester- 70%
Major constituent of gall stone; correlated with atherosclerosis & CHD
Blood levels are influenced by both genetic and environmental factors

12. FACTORS AFFECTING SERUM
CHOLESTEROL LEVEL
• Hereditary factors
• Diet
• Beneficial- Unsaturated fats (ω₆, ω₃ FA)
• Harmful- Saturated fat, sucrose, fructose
• Lifestyle- High blood pressure, smoking, male gender,
obesity, lack of exercise, soft drinks, emotional stress
• Hypolipidemic drug (atorvastatin, simvastatin,
Fluvastatin)- when diet change fail

13. DISORDER OF CHOLESTEROL METABOLISM
Familial
Hypercholesterolemia
Inherited defects in LP
metabolism
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

14. Thank You