Oxidation of unsaturated fatty acids by human fibroblasts with very-long-chain acyl-CoA dehydrogenase deficiency: aspects of substrate specificity and correlation with clinical phenotype

The degradation of unsaturated fatty acids was examined in fibroblasts from 16 patients with very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency . Analysis of acylcarnitine intermediates following incubation of intact hu man cells with these compounds revealed that the milder clinical phenotypes could be distinguished from the severe cardiomyopathic phenotype, These fi ndings, may reflect more effective contributions of alternate pathways in t he milder forms of the disease. Incubation of VI-CAD-deficient cells with c is-9 or trans-9 unsaturated fatty acids indicate that VLCAD is largely resp onsible for the 2,3-dehydrogenation of cis-5 or trans-5 intermediates in fi broblasts. The first two cycles of P-oxidation with oleic and linoleic acid s occur in the absence of VLCAD activity suggesting the presence of an addi tional acyl-CoA dehydrogenase or alternate pathway for the oxidation of the se unsaturated fatty acids. These observations have clinical relevance for determining diagnosis, prognosis and strategies for dietary treatment of th ese patients. (C) 2001 Elsevier Science BN, All rights reserved.