Ceramide biosynthesis in mouse brain microsomes: Comparison between C57/BL controls and quaking mutants

The biosynthesis of ceramides by mouse brain microsomes from sphingosine and stearoyl or lignoceroyl CoA was investigated. Microsomes from Quaking and normal mice showed similar activities when the acyl donor was stearate, but the Quaking mice exhibited about 55% less activity than normals when the acyl donor was lignocerate. This is interpreted to support the previous conclusion that two acyl transferases are involved in the synthesis of the nonhydroxy ceramides. It would appear that the lack of the lignoceroyl transferase is a specific aspect of the Quaking disorder. The composition of the components of cerebrosides from the brains of normal and Quaking mice was determined. An increased proportion of dihydrosphingosine and glucocerebroside was observed in the lipid from the mutants. A relative lack of the very long chain nonhydroxy acids was also observed, in confirmation of previous observations. The acyltransferase catalyzing stearoyl sphingosine formation was found to be unstable when incubated without substrates for 30 min, but considerable stabilization by sphingosine was observed.