What Is Cholesterol Biosynthesis?

B. Chisholm

The process within the body to produce cholesterol is called cholesterol biosynthesis. It consists of a number of steps which rely on numerous enzymes and processes to reach the final product. Cholesterol is essential for normal functioning of the body, in the right amount. It is used for manufacture of cell walls and hormones, amongst other functions. Too much cholesterol, however, can cause atherosclerosis, or narrowing of the blood vessels, and result in cardiac disease, heart attacks or stroke.

Cholesterol is produced through a process called cholesterol biosynthesis.
Cholesterol is produced through a process called cholesterol biosynthesis.

Cholesterol biosynthesis occurs mainly in the liver and starts with the raw product from food eaten by the person - carbohydrates, fats and proteins. These are metabolized in the body to a product called Acetyl CoA which is then further metabolized through a number of stages by the enzymes acetoacetyl CoA Thiolase, HMG CoA Synthase and HMG CoA Reductase to a product called mevalonate. It is at this point in cholesterol biosynthesis that the statins, one of the most widely used drugs for high cholesterol, act.

Statins are commonly used to treat high blood pressure.
Statins are commonly used to treat high blood pressure.

Mevalonate is further processed through a number of products by the enzymes Mevalonate Kinase, Phosphomevalonate Kinase, Phosphomevalonate Decarboxylase and Prenyltransferase to produce isoprenes. These then undergo further metabolism to either squalene or Coenzyme Q10, or ubiquinone. Coenzyme Q10 is an antioxidant.

High levels of low-density lipoprotein cholesterol in the blood may lead to clogged arteries.
High levels of low-density lipoprotein cholesterol in the blood may lead to clogged arteries.

Squalene is converted by Squalene Epoxidase and Oxidosqualene cyclase to lanosterol. The lanosterol undergoes various further processes to result in the final product of cholesterol. This is a highly simplified explanation of cholesterol biosynthesis and each step may include a number of processes, each one requiring specific enzymes. This, again, highlights the complexity of the systems of the body.

As mentioned earlier, too much cholesterol is not good and high cholesterol levels need to be treated, firstly with lifestyle changes such as diet and exercise and then, where necessary, by treatment with medications. The most well-known class of drugs used to treat high cholesterol is the HMG CoA Reductase inhibitors, or statins. These include atorvastatin, pravastatin and rosuvastatin, which are available by different trade names in different countries, usually by prescription only.

The statins work by inhibiting the action of the enzyme, HMG Co A Reductase, which forms part of cholesterol biosynthesis in the step that produces mevalonate. By inhibiting the enzyme, the conversion to mevalonate is decreased and therefore cholesterol is lowered. As with any medication, statins may interact with other drugs, be contraindicated in certain conditions and cause adverse side effects in some people. They should only be used under supervision of a medical professional.

Cholesterol biosynthesis starts with the raw product from food eaten by a person.
Cholesterol biosynthesis starts with the raw product from food eaten by a person.

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