LACK OF INVITRO CERAMIDE FORMATION IN THE PNS OF TREMBLER MICE

The amidification of sphingosine by acyl donors has been investigated in a microsomal fraction prepared from sciatic nerves of normal and Trembler mice. In the control, a ceramide synthesis is observed in the presence of acyl-CoAs and not with free fatty acids. The synthesis increases as a function of the protein amount and the time and is dependent on acyl-CoA concentration. The level of synthesis is highly similar to that observed in vivo after palmitate injection into the sciatic nerves of normal mice. In the mutant, there is a major abnormality because a weak synthesis (20% of the control) is observed only with high acyl-CoA concentration (>200-mu-M), whereas in the range of the physiological acyl-CoA concentrations (<20-mu-M), there is no ceramide formation from stearoyl-CoA or lignoceroyl-CoA.