1.7. Cholesterol metabolism

Steroids of human tissues form four groups:

1. Sterines with eight-carbon branch (the basic representative is cholesterol);

2. Bile acids the branch of which contains five carbon atoms;

3. Corticosteroids and progesterone with two-carbon branch;

4. Female and male gonadal hormones (estrogens and androgens) the branch of which in position 17 is not present at all.

Distribution and functions of cholesterol

In human tissues there are about 140 g of cholesterol; the amount of bile acids is about 5 g, other steroids are founded in small amounts. Part of cholesterol is esterified, it is done more often by oleic or linoleic acids. Cholesterol esters are generally in transport form (in blood lipoproteins) or the deposited form (for example, in cells of adrenal glands as lipid drops in cytoplasm). In erythrocytes there is only free cholesterol, and only in membranes.

Cholesterol Cholesterol ether

Cholesterol is a part of cellular membranes; it serves as the precursor in the synthesis of other steroids: bile acids, steroid hormones, vitamin D₃.

The average concentration of cholesterol in an organism is 0,2%, the same concentration of cholesterol is in blood. In the nervous system the amount of cholesterol is 2%, in cells of adrenal glands is 10%. Cholesterol in adrenal glands is used for synthesis of steroid hormones.

Cholesterol is synthesized in the organism. The organism of an adult receives daily 300-500 mg of cholesterol with nutrition, partially in the form of esters. Esters break down by the enzyme cholesterol esterase, which is contained in pancreatic and intestinal juices. Cholesterol is absorbed in small intestine mainly as a part of mixed micelles consisting of bile acids, fatty acids, monoglycerides, phospholipids, lysophospholipids.

Cholesterol biosynthesis

All carbon atoms of cholesterol are from acetate. Synthesis of cholesterol includes more than 35 enzymatic reactions. Most of cholesterol - about 80% - is synthesized in liver (in microsomes), in small intestines cells there are about 10%, in skin cells there are 5%. 1,3 g of cholesterol is formed daily in a human body in total.

1. Conversion of active acetate into mevalonic acid.

Acetoacetyl-CoA is formed as a result of 2 molecules of acetyl-CoA condensation. It reacts with the third molecule of acetyl-CoA and forms β-hydroxy-β-methylglutaryl-CоА.

Then in HMG-CoA-reductase reaction under the action of the enzyme HMG-CoA reductase it is reduced to mevalonic acid. This irreversible reaction is a rate-limiting in cholesterol biosynthesis.

2. Squalene formation from mevalonic acid.

Mevalonic acid is phosphorylated by ATP and participates in a series of reactions. Farnesylpyrophosphate (С₁₅) is formed as a result. Then 2 molecules of farnesylpyrophosphate condense and are reduced with NADPН, forming squalene (С₃₀).

3. Conversion of squalene to cholesterol. First lanosterol is formed which then turns to cholesterol.