Physiology of Cholesterol

Cholesterol is primarily synthesized from acetyl CoA through the HMG-CoA reductase pathway in many cells/tissues. About 20–25% of total daily production (~1 g/day) occurs in the liver, other sites of higher synthesis rates include the intestines, adrenal glands and reproductive organs.

For a person of about 150 pounds (68 kg), typical total body content is about 35 g, typical daily internal production is about 1 g and typical daily dietary intake is 200 to 300 mg. Of the 1,200 to 1,300 mg input to the intestines (via bile production and food intake), about 50% is typically reabsorbed into the bloodstream.


Cholesterol is minimally soluble in water; it cannot dissolve and travel in the water-based bloodstream. Instead, it is transported in the bloodstream by lipoproteins; protein “molecular-suitcases” which are water soluble and carry cholesterol and fats internally. The proteins forming the surface of the given lipoprotein particle determine from what cells cholesterol will be removed and to where it will be supplied.

The largest lipoproteins, which primarily transport fats from the intestinal mucosa to the liver are called chylomicrons. They carry mostly triglyceride fats and cholesterol (both from food and especially internal cholesterol secreted by the liver into the bile).

In the liver, chylomicron particles give up triglycerides and some cholesterol and are converted into low-density lipoprotein (LDL) particles which carry triglycerides and cholesterol on to other body cells.

In healthy individuals the LDL particles are large and relatively few in number. Conversely, large numbers of small LDL particles are strongly associated with promoting atheromatous disease within the arteries. (Lack of information on LDL particle number and size is one of the major problems of conventional lipid tests.)

High density lipoprotein (HDL) particles transport cholesterol back to the liver for excretion, but vary considerably in their effectiveness for doing this. Having large numbers of large HDL particles correlates with better health outcomes.

Conversely, having small amounts of large HDL particles is strongly associated with atheromatous disease progression within the arteries. (Note that the concentration of total HDL does not indicate the actual number of functional large HDL particles, another of the major problems of conventional lipid tests.)

The cholesterol molecules present in LDL cholesterol and HDL cholesterol are identical. The difference between the two cholesterol derives from the carrier protein molecules; the lipoprotein component.

Top Photo by Ed Uthman