Regulation of Cholesterol

The synthesis and utilization of cholesterol must be tightly regulated in order to prevent over-accumulation and abnormal deposition within the body.

Biological

HMG-CoA Reductase: http://www.macchess.cornell.edu/MacCHESS_publications/Deisenhofer_Istvan_01.html

HMG-CoA Reductase, the rate-determining step on the pathway for synthesis of cholesterol, is a major control point.

Short-term regulation

HMG-CoA Reductase is inhibited by phosphorylation, catalyzed by AMP-Dependent Protein Kinase. This kinase is active when cellular AMP (adenosine monophosphate) is high, corresponding to when ATP (adenosine triphosphate) is low. Thus, when cellular ATP is low, energy is not expended in synthesizing cholesterol.

Long-term regulation of cholesterol synthesis is by varied formation and degradation of HMG-CoA Reductase and other enzymes of the pathway for synthesis of cholesterol.

Medical

http://atkins.com/Archive/2001/12/13-350452.html

Changes in diet, lifestyle and exercise can help lower and maintain levels of LDL blood cholesterol. However, in some cases other factors such as genetics make the use of drugs necessary to treat the problem.

The statins work within the liver to directly prevent the formation of cholesterol by inhibiting HMG-CoA reductase.

The resins bind bile acids, causing the liver to produce more of them and metabolising cholesterol in the process.

The fibrates lower triglycerides and LDL levels and can increase HDL levels. They have been found to reduce the risk of a second heart attack

The disadvantages of these drugs are that they can be fairly expensive and are often required for many years or even a whole lifetime. Liver damage can also be caused by some of the pharmaceuticals used.