title: Impaired mitochondrial fatty acid oxidative flux in fibroblasts from a patient with malonyl-CoA decarboxylase deficiency.
abstract: Malonyl-CoA decarboxylase deficiency is a rare inborn error of metabolism. It has been suggested but never demonstrated that many of the clinical features arise due to inhibition of mitochondrial fatty acid oxidation by accumulated malonyl-CoA. We studied the oxidation of fatty acids in cultured skin fibroblasts from a recently described patient with malonyl-CoA decarboxylase deficiency. There was a marked reduction in the oxidation of palmitic and myristic acids both under baseline conditions and when the cells were cultured in the presence of high concentrations of acetate, a malonyl-CoA precursor. These results suggest that there is inhibition of fatty acid oxidation in malonyl-CoA decarboxylase deficiency and that this inhibition may be related to some of the clinical phenotypes.
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center at Dallas, USA. michaelj.bennett@email.swmed.edu
authors.forename: M J
authors.initials: MJ
authors.lastname: Bennett
authors.forename: P A
authors.initials: PA
authors.lastname: Harthcock
authors.forename: R L
authors.initials: RL
authors.lastname: Boriack
authors.forename: J C
authors.initials: JC
authors.lastname: Cohen
mesh_terms: D002262:Carboxy-Lyases / Q000172:deficiency*; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D018076:DNA, Complementary / Q000378:metabolism; D005091:Exons; D005227:Fatty Acids / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009227:Myristic Acids / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D019308:Palmitic Acid / Q000378:metabolism; D010641:Phenotype; D012867:Skin / Q000166:cytology
chemical_list: D018076:DNA, Complementary; D005227:Fatty Acids; D009227:Myristic Acids; D019308:Palmitic Acid; D002334:Carnitine O-Palmitoyltransferase; D002262:Carboxy-Lyases; C021532:malonyl-CoA decarboxylase; D010100:Oxygen