Identification of the peroxisomal β-oxidation enzymes involved in the biosynthesis of docosahexaenoic acid

Sacha Ferdinandusse, Simone Denis, Petra A.W. Mooijer, Zhongyi Zhang, Janardan K. Reddy, Arthur A. Spector, Ronald J.A. Wanders*

*Corresponding author for this work

Research output: Contribution to journalArticle

137 Scopus citations

Abstract

DHA (C22:6n-3) is an important PUFA implicated in a number of (patho)physiological processes. For a long time, the exact mechanism of DHA formation has remained unclear, but now it is known that it involves the production of tetracosahexaenoic acid (C24:6n-3) from dietary linolenic acid (C18:3n-3) via a series of elongation and desaturation reactions, followed by β-oxidation of C24:6n-3 to C22:6n-3. Although DHA is deficient in patients lacking peroxisomes, the intracellular site of retroconversion of C24:6n-3 has remained controversial. By making use of fibroblasts from patients with defined mitochondrial and peroxisomal fatty acid oxidation defects, we show in this article that peroxisomes, and not mitochondria, are involved in DHA formation by catalyzing the β-oxidation of C24:6n-3 to C22:6n-3. Additional studies of 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, and of fibroblasts from L-bifunctional protein and sterol carrier protein X (SCPx) knockout mice, show that the main enzymes involved in β-oxidation of C24:6n-3 to C22:6n-3 are SCOX, DBP, and both 3-ketoacyl-CoA thiolase and SCPx. These findings are of importance for the treatment of patients with a defect in peroxisomal β-oxidation.

Original languageEnglish (US)
Pages (from-to)1987-1995
Number of pages9
JournalJournal of lipid research
Volume42
Issue number12
StatePublished - 2001

Keywords

  • 3-ketoacyl-CoA thiolase
  • D-bifunctional protein
  • Linolenic acid
  • Peroxisomal and mitochondrial fatty acid oxidation disorders
  • Polyunsaturated fatty acids
  • Sterol carrier protein X
  • Straight-chain acyl-CoA oxidase
  • Tetracosahexaenoic acid

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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