CHOLESTEROL SYNTHESIS

I. Synthesized by virtually all tissues but primarily by:

Liver
Intestine
Adrenal cortex
Reproductive Tissue
(Testes, ovaries, placenta)

II. Cholesterol is a component of all cell membranes & is a precursor of

Bile acids (in liver)

Steroid hormones (endocrine tissues)
Vitamin D (by a series of tissues)

III. The liver plays a central role in cholesterol regulation

Sources of cholesterol into the liver:
1. Dietary-chylomicron remnants from the small intestine
2. Extra hepatic cholesterol-reaches liver carried in HDL
3. Synthesized De Novo

Cholesterol leaves the liver

1. Secretion of HDL & VLDL

2. Free cholesterol secreted in bile
3. Conversion to bile acids/salts

Cholesterol 4 ring hydrophobic compound

IV. All the carbon atoms in cholesterol come from:

Acetyl CoA (Major carbon source is glucose)

(a) 2 acetyl CoA molecules condense to form = Acetoacetyl CoA
(b) 3 acetyl CoA is added forming = HMG CoA

NOTE: ****HMG CoA is a key intermediate in cholesterol biosynthesis. In the

endoplasmic reticulum, its reduced to mevalonic acid by the regulatory enzyme HMG CoA
reductase. HMG CoA reductase is by cholesterol & bile salts in the liver & is induced when
blood insulin levels are elevated.

V. Mevalonic Acid is phosphorylated & decarboxylated to form isopentenyl pyrophosphate.

VI: Thru a series of steps, cholesterol is formed.

(A) Glucosan favors the production of an inactive form of HMG CoA reductase.

(B) Cholesterol synthesis is also regulated by the amount of cholesterol taken up by the
cells. Chylomicron remnants internalized by liver cells & LDL internalized by cells of
the liver & peripheral tissues provide cholesterol with De Novo synthesis.