title: 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.
abstract: 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 human cells with these compounds revealed that the milder clinical phenotypes could be distinguished from the severe cardiomyopathic phenotype. These findings may reflect more effective contributions of alternate pathways in the milder forms of the disease. Incubation of VLCAD-deficient cells with cis-9 or trans-9 unsaturated fatty acids indicate that VLCAD is largely responsible for the 2,3-dehydrogenation of cis-5 or trans-5 intermediates in fibroblasts. The first two cycles of beta-oxidation with oleic and linoleic acids occur in the absence of VLCAD activity suggesting the presence of an additional acyl-CoA dehydrogenase or alternate pathway for the oxidation of these unsaturated fatty acids. These observations have clinical relevance for determining diagnosis, prognosis and strategies for dietary treatment of these patients.
authors.affiliation: The Kimberly S. Courtwright and Joseph W. Summers Institute of Metabolic Disease, Baylor University Medical Center, Dallas, TX 75226, USA. ds.roe@baylordallas.edu
authors.forename: D S
authors.initials: DS
authors.lastname: Roe
authors.forename: C
authors.initials: C
authors.lastname: Vianey-Saban
authors.forename: S
authors.initials: S
authors.lastname: Sharma
authors.forename: M T
authors.initials: MT
authors.lastname: Zabot
authors.forename: C R
authors.initials: CR
authors.lastname: Roe
mesh_terms: D044942:Acyl-CoA Dehydrogenase, Long-Chain; D044944:Acyl-CoA Dehydrogenases / Q000172:deficiency*; D000328:Adult; D002331:Carnitine / Q000031:analogs & derivatives* / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007536:Isomerism; D008052:Lipid Metabolism, Inborn Errors / Q000378:metabolism* / Q000473:pathology; D019301:Oleic Acid / Q000378:metabolism; D009829:Oleic Acids / Q000378:metabolism; D010084:Oxidation-Reduction; D013379:Substrate Specificity
chemical_list: D005231:Fatty Acids, Unsaturated; D009829:Oleic Acids; C116917:acylcarnitine; D019301:Oleic Acid; C011459:elaidic acid; D044944:Acyl-CoA Dehydrogenases; D044942:Acyl-CoA Dehydrogenase, Long-Chain; C050413:11-octadecenoic acid; D002331:Carnitine