Cholesterol is an animal sterol which occurs either free or as fatty esters. As it was first isolated from human gallstones deposited in the bile duct, it is named as cholesterol (Greek word chole means – bile, sterol). Cholesterol is composed of 1,2-cyclopentanoperhydrophenanthrene ring system. Although cholesterol is an essential compound for life for the synthesis of hormones, bile acids and vitamin D, it is not necessary to supply it in the diet because it can be synthesised in the cell from acetyl CoA Carbohydrates, amino acids, fatty acids and glycerol which gets converted to Acetyl CoA can also serve as a source for cholesterol synthesis. The liver plays a decisive role in the cholesterol metabolism which accounts for 90% of the overall endogenic cholesterol and its esters.
A man weighing 70 kg contains about 140 grams of cholesterol. The cholesterol concentration of blood in human is between 150 to 250 mg per 100 ml, being distributed equally between the cells and the plasma. The half life of cholesterol is about 8 to 12 days.
Important intermediates of cholesterol Biosynthesis and enzymes involved.
A molecule of acetic acid combines with coenzyme A (CoA) to produce Acetyl CoA in the presence of an enzyme Acetyl CoA synthetase.
Two molecules of acetyl-CoA condense to form an acetoacetyl-CoA molecule, catalyzed by the enzyme “thiolase”.
The acetoacetyl-CoA further undergoes condensation with one more molecule of acetyl-CoA to form HMG-CoA (3-Hydroxy 3-Methyl Glutaryl-CoA). The enzyme which mediates this reaction is called HMG-CoA synthetase.
The HMG-CoA is reduced to form mevalonate by NADPH + H+ dependent reductase (HMG-CoA reductase). This is the rate limiting enzyme in the pathway of cholesterol biosynthesis.
5. Mevalonate thus formed is then converted to squalene through various steps.
6. Squalene, with the formation of various intermediates finally give rise to the end product cholesterol.
In the body cholesterol is converted into several other types of biologically important steroids, viz. bile acids, bile salts and Vitamin D.
Bile acids are of two types namely primary and secondary bile acids. Primary bile acids include cholic acid and chenodeoxy cholic acid and secondary bile acids include deoxycholic acid and lithocholic acid.
Bile acids are C24 steroids, detergent like compounds that are responsible for the emulsification and absorption of lipids in the intestine.
Cholic acid is conjugated in the liver with either glycine or taurine through peptide linkages forming the bile salts glycocholic acid and taurocholic acid respectively. They combine with sodium and potassium present in the bile and form water soluble alkaline bile salts, namely sodium glycocholate and sodium taurocholate respectively.
· Bile salts are the digestion promoting constituents of bile.
· They lower surface tension and thus can emulsify fats.
· They also activate lipases.
Vitamin D is produced by irradiation of 7-dehydrocholesterol in the skin and in the kidney.
Vitamin D is a derivative of cholesterol and the precursor of para thyroid hormone which regulates calcium and phosphate metabolism in vertebrates.
Phospholipids are so designated because they contain phosphoric acid. They are present in all cells, plants as well as animals. They are present both in cytoplasm as well as in the cell membranes and serve important functions in both cell activity and cell permeability. Phospholipids are made up of fatty acids, nitrogenous base, phosphoric acid and glycerol or other alcohol. Phospholipids can be classified based on the alcohol moiety of the phospholipid as follows.
Glycerol is the alcohol moiety in this group. This include lecithins, cephalins, phosphatidyl serine, plasmalogens and diphosphatidyl glycerols.
In this the cyclic hexahydric alcohol “inositol” replaces the nitrogenous base.
In this group of substances, glycerol is replaced by a complex amino alcohol “Sphingosine”. These are clinically important phospholipids in human.