Cholesterol - CAS 57-88-5

Cholesterol homeostasis is vital for proper cellular and systemic functions. Disturbed cholesterol balance underlies not only cardiovascular disease but also an increasing number of other diseases such as neurodegenerative diseases and cancers. The cellular cholesterol level reflects the dynamic balance between biosynthesis, uptake, export and esterification - a process in which cholesterol is converted to neutral cholesteryl esters either for storage in lipid droplets or for secretion as constituents of lipoproteins. In this Review, we discuss the latest advances regarding how each of the four parts of cholesterol metabolism is executed and regulated. The key factors governing these pathways and the major mechanisms by which they respond to varying sterol levels are described. Finally, we discuss how these pathways function in a concerted manner to maintain cholesterol homeostasis.

Cholesterol has evolved to fulfill sophisticated biophysical, cell signaling and endocrine requirements of animal systems. At a cellular level, cholesterol is found in membranes, where it increases both bilayer stiffness and impermeability to water and ions. Furthermore, cholesterol is integrated into specialized lipid-protein membrane microdomains with critical topographical and signaling functions. At an organismal level, cholesterol is the precursor for all steroid hormones, including gluco- and mineralo-corticoids, sex hormones and vitamin D, all of which regulate carbohydrate, sodium, reproductive and bone homeostasis, respectively. This sterol is also the precursor for bile acids, which are important for intestinal absorption of dietary lipids as well as energy and glucose metabolic regulation. Importantly, complex mechanisms maintain cholesterol within physiological ranges and the disregulation of these mechanisms results in embryonic or adult diseases, caused by either excessive or reduced tissue cholesterol levels. The causative role of cholesterol in these diseases has been demonstrated by diverse genetic and pharmacologic animal models that are commented in this review.

Cholesterol is an important molecule in humans and both its excess and its deficiency cause disease. Most clinicians appreciate its role in stabilizing cellular plasma membranes but are unaware of its myriad other functions. This review highlights cholesterol's newly recognized important roles in human physiology and pathophysiology. The basis for cholesterol's ubiquitous presence in eukaryote organisms is its three part structure involving hydrophilic, hydrophobic, and rigid domains. This structure permits cholesterol to regulate multiple cellular processes ranging from membrane fluidity and permeability to gene transcription. Cholesterol not only serves as a molecule of regulation itself, but also forms the backbone of all steroid hormones and vitamin D analogs. Cholesterol is responsible for growth and development throughout life and may be useful as an anticancer facilitator. Because humans have a limited ability to catabolize cholesterol, it readily accumulates in the body when an excess from the diet or a genetic abnormality occurs. This accumulation results in the foremost cause of death and disease (atherosclerosis) in the Western world. Identification of cholesterol's disease-producing capabilities dates back 5,000 years to the Tyrolean iceman and more recently to ancient mummies from many cultures throughout the world. In contrast, a deficiency of cholesterol in the circulation may result in an inability to distribute vitamins K and E to vital organs with serious consequences. Understanding the benefits and hazards of cholesterol in the clinical setting will improve the endocrinologist's ability to control diseases associated with this unique molecule.