Cell compartmentalization of cholesterol biosynthesis.

Thus, the results showing the presence of cholesterol synthetic enzymes in peroxisomes (see references 1, 4, 5, 6, 7, 8, 12, 13, 20, 21, 22, 24, 25, and 26), the reduced levels of cholesterol synthesis enzymes and cholesterol synthetic capacity of cells and tissues lacking peroxisomes, 26, 37, 39 and the low serum cholesterol levels in patients suffering from peroxisomal deficiency diseases40-43 demonstrate that peroxisomes are essential for normal cholesterol synthesis. A number of metabolic pathways require co-participation of enzymes located in both peroxisomes as well as enzymes found in other intracellular compartments. For example, the first steps of plasmalogen synthesis occur in the peroxisomes, while the terminal reactions are completed in the endoplasmic reticulum. Similarly, the oxidation of cholesterol to bile acids requires the participation of enzymes localized in the endoplasmic reticulum as well as peroxisomes. Little is known about the regulation of such pathways or about the shuttling of intermediates between compartments. The physiological importance of peroxisomal enzymes in the regulation of sterol metabolism remains to be clarified.