farnesyl-pyrophosphate and Peroxisomal-Disorders

Topics: Acetyl Coenzyme A; Animals; Cholesterol; Humans; Liver; Mice; Mice, Knockout; Peroxisomal Disorders; Peroxisomes; Polyisoprenyl Phosphates; Rats; Sesquiterpenes; Terpenes

Peroxisomes contain enzymes catalyzing a number of indispensable metabolic functions mainly related to lipid metabolism. The importance of peroxisomes in man is stressed by the existence of genetic disorders in which the biogenesis of the organelle is defective, leading to complex developmental and metabolic phenotypes. The purpose of this review is to emphasize some of the recent findings related to the localization of cholesterol biosynthetic enzymes in peroxisomes and to discuss the impairment of cholesterol biosynthesis in peroxisomal deficiency diseases.

Topics: Acyl Coenzyme A; Cholesterol; Disease Models, Animal; Embryonic and Fetal Development; Humans; Peroxisomal Disorders; Peroxisomes; Polyisoprenyl Phosphates; Sesquiterpenes

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.

Topics: Acetyl-CoA C-Acyltransferase; Animals; Carboxy-Lyases; Carrier Proteins; Cell Compartmentation; Cholesterol; Farnesyl-Diphosphate Farnesyltransferase; Humans; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Synthase; Lanosterol; Liver; Mevalonic Acid; Microbodies; Peroxisomal Disorders; Phosphotransferases (Alcohol Group Acceptor); Phosphotransferases (Phosphate Group Acceptor); Plant Proteins; Polyisoprenyl Phosphates; Rats; Sesquiterpenes; Squalene