High metabolism and subsequent elongation of 3-hydroxyeicosanoyl-CoA in very-long-chain fatty acid deficient PNS of Trembler mice

The developmental patterns of the overall fatty acid elongation and of the last two partial activities of microsomal elongase (dehydration and reducti on of 3-hydroxyacyl-CoA) were investigated in the PNS of normal and Tremble r mice. Unexpectedly, Trembler microsomes synthesized norm al C22-CoA amoun ts from 3-hydroxyeicosanoyl-CoA (3-OHC20-CoA), a C18-CoA elongation interme diate. Hydroxy-acyl-CoA dehydrase and enoyl-CoA reductase activities were f ound to be higher in the mutant than in the control, whatever the stage of development. Moreover, C20-CoA elongation led to normal C22-CoA and C24-CoA formation in the mutant whereas C20-CoA formation from C18-CoA was always far lower in Trembler than in control. C18-CoA condensing enzyme emerges as the only elongation step involved in the VLCFA deficit evidenced in Trembl er PNS. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.