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Journal of Lipid Research, Vol. 45, 1104-1111, June 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Identification of the peroxisomal ß-oxidation enzymes involved in the degradation of long-chain dicarboxylic acids

Sacha Ferdinandusse^1,*, Simone Denis^*, Carlo W. T. van Roermund^*, Ronald J. A. Wanders^*, and Georges Dacremont

^* Departments of Clinical Chemistry, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Pediatrics, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Department of Pediatrics, University of Ghent, Ghent, Belgium

¹ To whom correspondence should be addressed. e-mail: s.ferdinandusse{at}amc.uva.nl

Dicarboxylic acids (DCAs) are -oxidation products of monocarboxylic acids. After activation by a dicarboxylyl-CoA synthetase, the dicarboxylyl-CoA esters are shortened via ß-oxidation. Although it has been studied extensively where this ß-oxidation process takes place, the intracellular site of DCA oxidation has remained controversial. Making use of fibroblasts from patients with defined mitochondrial and peroxisomal fatty acid oxidation defects, we show in this paper that peroxisomes, and not mitochondria, are involved in the ß-oxidation of C16DCA. Additional studies in fibroblasts from patients with X-linked adrenoleukodystrophy, straight-chain acyl-CoA oxidase (SCOX) deficiency, D-bifunctional protein (DBP) deficiency, and rhizomelic chondrodysplasia punctata type 1, together with direct enzyme measurements with human recombinant L-bifunctional protein (LBP) and DBP expressed in a fox2 deletion mutant of Saccharomyces cerevisiae, show that the main enzymes involved in ß-oxidation of C16DCA are SCOX, both LBP and DBP, and sterol carrier protein X, possibly together with the classic 3-ketoacyl-CoA thiolase.

This is the first indication of a specific function for LBP, which has remained elusive until now.

Abbreviations: ALDP, adrenoleukodystrophy protein; BCOX, branched-chain acyl-CoA oxidase; CACT, carnitine acylcarnitine translocase; CPT, carnitine palmitoyltransferase; DBP, D-bifunctional protein; DCA, dicarboxylic acid; LBP, L-bifunctional protein; MTP, mitochondrial trifunctional protein; PBD, peroxisome biogenesis disorder; RCDP, rhizomelic chondrodysplasia punctata; SCOX, straight-chain acyl-CoA oxidase; SCPx, sterol carrier protein X; VLCAD, very long-chain acyl-CoA dehydrogenase; XALD, X-linked adrenoleukodystrophy

Supplementary key words straight-chain acyl-CoA oxidase • L-bifunctional protein • D-bifunctional protein

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