title: Biochemical characterization of two functional human liver acyl-CoA oxidase isoforms 1a and 1b encoded by a single gene.
abstract: Human acyl-CoA oxidase 1 (ACOX1) is a rate-limiting enzyme in peroxisomal fatty acids beta-oxidation and its deficiency is associated with a lethal, autosomal recessive disease, called pseudoneonatal-adrenoleukodystrophy. Two mRNA variants, transcribed from a single gene encode ACOX1a or ACOX1b isoforms, respectively. Recently, a mutation in a splice site has been reported [H. Rosewich, H.R. Waterham, R.J. Wanders, S. Ferdinandusse, M. Henneke, D. Hunneman, J. Gartner, Pitfall in metabolic screening in a patient with fatal peroxisomal beta-oxidation defect, Neuropediatrics 37 (2006) 95-98.], which results in the defective peroxisomal fatty acids beta-oxidation. Here, we show that these mRNA splice variants are expressed differentially in human liver. We investigated the biochemical role of the two human ACOX1 isoforms by heterologous expression of the catalytically active ACOX1a and ACOX1b enzymes in Escherichia coli. ACOX1a seems to be more labile and exhibits only 50% specific activity toward palmitoyl-CoA as compared to ACOX1b.
authors.affiliation: INSERM, U866, Dijon F-21000, France.
authors.forename: David
authors.initials: D
authors.lastname: Oaxaca-Castillo
authors.forename: Pierre
authors.initials: P
authors.lastname: Andreoletti
authors.forename: Aurore
authors.initials: A
authors.lastname: Vluggens
authors.forename: Sangtao
authors.initials: S
authors.lastname: Yu
authors.forename: Paul P
authors.initials: PP
authors.lastname: van Veldhoven
authors.forename: Janardan K
authors.initials: JK
authors.lastname: Reddy
authors.forename: Mustapha
authors.initials: M
authors.lastname: Cherkaoui-Malki
mesh_terms: D042962:Acyl-CoA Oxidase / Q000737:chemistry* / Q000235:genetics*; D004789:Enzyme Activation; D004795:Enzyme Stability; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics; D008099:Liver / Q000201:enzymology*; D008970:Molecular Weight
chemical_list: D007527:Isoenzymes; D042962:Acyl-CoA Oxidase