Autoregulation of cholesterol synthesis: physiologic and pathophysiologic consequences.
Autoregulation of cholesterol synthesis focuses on the 19 metabolic steps from lanosterol to cholesterol. Although synchronization of their rates of synthesis in all tissues was the paradigm, a known exception occurs in the ovary where a local increase in a sterol intermediate, FF-MAS (follicular fluid meiosis activating sterol), activates meiosis during oocyte maturation. Mutations in the genes that govern synchronization cause an increase in sterol intermediates that follow an alternate, oxysterol, pathway of metabolism. Experimental models in animals imply that oxysterol metabolites are determinants of the dysmorphism that occurs during fetal development in these genetic diseases. These few examples may portend a much broader role for sterol intermediates and their novel oxysterol metabolites in physiologic and pathophysiologic processes.
Department of Medicine, NYU School of Medicine, New York, NY 10016, United States.
Robert J
RJ
Fakheri
Norman B
NB
Javitt
D000818:Animals; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics / Q000378:metabolism; D002782:Cholestenes / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis*; D000013:Congenital Abnormalities / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007810:Lanosterol / Q000378:metabolism; D008540:Meiosis; D009865:Oocytes / Q000378:metabolism
D002782:Cholestenes; D007810:Lanosterol; C100324:4,4-dimethylcholesta-8,14,24-trienol; D002784:Cholesterol; D053493:Cholestanetriol 26-Monooxygenase