Ceramidase and Signal Transduction

Abstract

The deacylation of ceramide to form sphingosine in cells is the result of the activity of a group of enzymes referred to as the ceramidases (EC 3.5.1.23). There is a lysosomal form with an acidic pH optimum, a form with an alkaline pH optimum that may be associated with the plasma membrane and a form with a neutral pH optimum with a more limited tissue distribution. These enzymes are important in the degradative pathway of ceramide and are the key enzymes in the formation of sphingosine. The activity of these enzymes therefore are major determinates of the relative concentrations of these two biologically active lipids in the cell. Since the publication of a recent review of ceramidase,1 studies have demonstrated that modulation of ceramidase results in changes in cell growth and apoptosis. Despite the potential importance of ceramidases, there is actually little known about their enzymology, although one acid form and one alkaline form have recently been purified. In addition there is nothing known of the molecular biology of ceramidase. It is the intent of this chapter to briefly review the known enzymology of ceramidases, describe briefly the effect of deficiency of the acid form (Farber’s disease) and then show how inhibitors of ceramidase have begun to demonstrate its biologic importance in the control of cell growth.KeywordsSodium CholateAcid CeramidaseCeramide AnalogCeramidase ActivitySphingomyelin CycleThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.