Modeling Cholesterol in Humans: Update and Dealing with the Problem of Exchange in Vivo Using the Blood Cell-Lipoprotein Paradigm

The cholesterol molecule, like some other lipids, is very weakly soluble in water. It is present in all cells of humans, mainly in membranes and especially in specialized areas of the plasma membrane such as caveolae and rafts. These areas are rich in sphingomye-lin and carry out important functions like signaling. Cholesterol is also present in plasma and bile, but it is nearly absent from normal urine and spinal fluid. In plasma, cholesterol is localized in lipoprotein particles; in bile, it is in vesicles and micelles. The common denominators at these locations are phosphatidylcholine and sphingomyelin. Cholesterol is very mobile in this phospholipid environment; it flip-flops across the bilayer with a t1/2 of seconds, diffuses laterally with similar speed, and exchanges/transfers between membranes in proximity by aqueous diffusion or with the facilitation of soluble lipid transfer proteins. The reasons why lipoproteins, bile vesicles, and areas of the plasma membrane are cholesterol enriched are active areas of investigation.