What Is Cholesterol Synthesis?

Every cell in the human body contains cholesterol, which is needed to produce certain hormones, make bile acid and to manufacture vitamin D. To ensure availability, the body makes its own supply in a biochemical process called cholesterol synthesis.

Synthesis Sites

• Approximately half of the cholesterol required by the body is produced via cholesterol synthesis. This process is carried out each day in the intestines and in the liver.

Cholesterol Precursors

• Cholesterol synthesis begins with acetyl-CoA, a byproduct generated when proteins, fats and carbohydrates are broken down to produce fuel for cells. The body is also capable of making acetyl-CoA by using acetyl-CoA synthetase to initiate the oxidation of ethanol.

Enzymatic Activity

• Numerous enzymes take over to create a cascade of reactions to eventually produce cholesterol. The first involves acetoacetyl CoA thiolase to make acetoacetyl CoA.

Reduction Reactions

• Cholesterol synthesis continues with the reduction of acetyl-CoAs to 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) and then to mevalonate. Note that statin drugs, such as Lipitor, interrupt the synthesis of cholesterol at this point.

Final Steps

• If statin drugs are not present, mevalonate is converted into isopentenyl pyrophosphate (IPP), which is then converted into squalene. Finally, squalene is converted into cholesterol.