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Correspondence to:
Ronald J. A. Wanders, at the University of Amsterdam Academic Medical Center, Departments of Clinical Chemistry and Pediatrics, Laboratory for Genetic Metabolic Diseases (F0-224), P.O. Box 22700, 1100 DE Amsterdam, The Netherlands., Wanders{at}amc.uva.nl (E-mail)
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 ß-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 ß-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 ß-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 ß-oxidation. — Ferdinandusse, S., S. Denis, P. A. W. Mooijer, Z. Zhang, J. K. Reddy, A. A. Spector, and R. J. A. Wanders. Identification of the peroxisomal ß-oxidation enzymes involved in the biosynthesis of docosahexaenoic acid. J. Lipid Res. 2001. 42: 1987–1995.
Supplementary key words:
D-bifunctional protein, 3-ketoacyl-CoA thiolase, linolenic acid, polyunsaturated fatty acids, straight-chain acyl-CoA oxidase, tetracosahexaenoic acid, peroxisomal and mitochondrial fatty acid oxidation disorders, sterol carrier protein X
Copyright © 2001 by Lipid Research, Inc.
Identification of the peroxisomal ß-oxidation enzymes involved in the biosynthesis of docosahexaenoic acid
Sacha Ferdinandussea,
Simone Denisa,
Petra A. W. Mooijera,
Zhongyi Zhangc,
Janardan K. Reddyc,
Arthur A. Spectord, and
Ronald J. A. Wandersa,b
a Department of Clinical Chemistry, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
b Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
c Department of Pathology, Northwestern University Medical School, Chicago, IL
d Department of Biochemistry, University of Iowa, Iowa City, IA
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