CHOLESTROL SYNTHESIS

Cholesterol Structure?

• Free cholesterol (30%)

• Cholesterol Ester - R-COO (70%)

Sources of cholesterol?

• Endogenous Source: 500-700mg. All nucleated cells can produce cholesterol.

• Exogenous Source: 300-500 mg. Comes from animal food such as lard, egg yolk, meat and etc.

Site of cholesterol synthesis?

body need upto 800mg/day of cholesterol per day.

Site: Cytosol and microsomal fraction of cells.

tissue: skin, ovaries testes, intestine and liver

Key Enzyme?

HMG-CoA Reductase

Role of Key Enzyme?

To convert HMG CoA to Mevalonate.

Starting material?

Acetyl CoA

What i the reaction pathway?

• Biosynthesis of a 6 Carbon Compound Mevalonate

• Formation of Isoprenoid Units.

• 6 Isoprenoid Units condense to form Squalene

• Formation of Lanosterol

• Formation of Cholesterol.

Regulation?

1. Feedback Repression:

• Allosteric Inhibitor: Cholesterol and Mevalonate (negative feedback)

• Allosteric Inhibitor: Acetyl CoA (positive feedback)

• When ↑ in cholesterol , it will inhibit HMG-CoA.

• When ↓ in cholesterol, it will activate HMG-CoA.

Regulation (cont.)

2. Covalent Regulation:

• In dephosphorylated form, HMG CoA Reductase is active by insulin and thyroid hormones stimulate cholesterol synthesis.

• In phosphorylated form, HMG CoA reductase is inactive by glucagon and glucocorticoids.

• In starvation, ↑ of glucagon and glucocorticoids therefore HMG CoA reductase is inactive.

Catabolism (Fate) of Cholesterol

1. Conversion to bile salts: 80% of cholesterol in liver is converted to bile acid or bile salt.

2. Conversion of 4 steroid hormones:

• Glucocorticoids (cortisol)

• Mineralocorticoids (aldosterone)

• Female Sex hormones (Progesterone)

• Male Sex hormones (Testosterone)

  3.Conversion of 7-dehydro cholesterol for the synthesis of Vitamin D.

  4. Conversion to cholestanol and caprostanol through excretion of feces.

  In intestine, cholesterol is converted to cholestanol and caprostanol by intestine bacterial flora, which is then excreted by feces.

Functions of Cholesterol?

• Cholesterol is used by the body to convert to bile salt which is necessary for digestion and absorption.

• Ovaries use cholesterol to form progesterone and oestrogen.

• Testes use cholesterol to form testosterone.

• Cholesterol in skin allows to prevent evaporation of water.

• Adrenal cortex uses cholesterol to form adrenocortical hormones.