title: Complementation analysis of fibroblasts from peroxisomal fatty acid oxidation deficient patients shows high frequency of bifunctional enzyme deficiency plus intragenic complementation: unequivocal evidence for differential defects in the same enzyme protein.
abstract: In the last few years many patients have been reported with a defect in peroxisomal fatty acid beta-oxidation of unknown origin. Using a combined approach based on direct activity measurements of straight-chain acyl-CoA oxidase and complementation analysis after somatic cell fusion of fibroblasts, we have now classified 13 patients into 4 distinct groups representing different gene defects. Remarkably, we found intragenic complementation in group 2 so that group 2 is in fact made up of 3 distinct subgroups. The underlying basis for this peculiar phenomenon probably has to do with the fact that bifunctional protein harbors two catalytic activities including enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase. In group 2A enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase are defective whereas in group 2B and 2C either the hydratase or 3-hydroxyacyl-CoA dehydrogenase component of the bifunctional protein is deficient.
authors.affiliation: University Hospital Amsterdam, Academic Medical Center, Division of Clinical Chemistry, The Netherlands.
authors.forename: E G
authors.initials: EG
authors.lastname: van Grunsven
authors.forename: C W
authors.initials: CW
authors.lastname: van Roermund
authors.forename: S
authors.initials: S
authors.lastname: Denis
authors.forename: R J
authors.initials: RJ
authors.lastname: Wanders
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency* / Q000235:genetics*; D002459:Cell Fusion; D002460:Cell Line; D004746:Enoyl-CoA Hydratase / Q000172:deficiency* / Q000235:genetics*; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism; D005347:Fibroblasts; D005816:Genetic Complementation Test; D006801:Humans; D007535:Isomerases; D009097:Multienzyme Complexes / Q000172:deficiency* / Q000235:genetics*; D010084:Oxidation-Reduction; D063994:Peroxisomal Bifunctional Enzyme; D018901:Peroxisomal Disorders / Q000201:enzymology* / Q000235:genetics; D015211:Zellweger Syndrome
chemical_list: D005227:Fatty Acids; D009097:Multienzyme Complexes; C002844:pristanic acid; D015094:3-Hydroxyacyl CoA Dehydrogenases; C576253:EHHADH protein, human; D004746:Enoyl-CoA Hydratase; D063994:Peroxisomal Bifunctional Enzyme; D007535:Isomerases