THE IN-SITU DEGRADATION OF CERAMIDE, A POTENTIAL LIPID MEDIATOR, IS NOT COMPLETELY IMPAIRED IN FARBER-DISEASE

The time course of degradation of a radiolabelled natural ceramide has been studied in intact, living lymphoid cells and skin fibroblasts fr om normal individuals and from patients affected with Farber disease, an inborn disorder of ceramide metabolism due to deficient activity of lysosomal ceramidase. The hydrolysis of ceramide in lysosomes was sel ectively followed by examining the turnover of an LDL-associated radio active sphingomyelin. This permitted to estimate accurately the effect ive lysosomal ceramidase activity and to demonstrate: (i) a very activ e catabolism of ceramide in normal cells; and (ii) the absence of a co mplete block of ceramide degradation in Farber cells. The possible imp lication of ceramide as a lipid mediator of the pathogenesis of Farber disease is discussed.