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Identification of the Enzymic Defect in X-Linked Adrenoleukodystrophy: Oxidation of Very Long Chain Fatty Acids is Deficient Due to an Impaired Ability of Peroxisomes to Activate Very Long Chain Fatty Acids

  • Conference paper
Lipid Storage Disorders

Part of the book series: NATO ASI Series ((NSSA,volume 150))

Abstract

Mitochondria were long thought to be the sole site of fatty acid β-oxidation. Following the discovery by Cooper and Beevers1 that castor bean endosperm glyoxysomes, organelles closely related to peroxisomes, contain a fatty acid β-oxidation system, peroxisomes from rat liver2 and various other mammalian tissues were subsequently found to catalyze fatty acyl-CoA β-oxidation as well (reviewed in Refs. 3-6). Like mitochondrial fatty acid β-oxidation, peroxisomal fatty acid β-oxidation proceeds via successive steps of dehydrogenation, hydration, dehydrogenation and thiolytic cleavage. These reactions are catalyzed by the specific peroxisomal β-oxidation enzyme proteins acyl-CoA oxidase (EC 1.3.99.3), the bifunctional protein with enoyl-CoA hydratase (EC 4.2.1.17) and 3-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.35) activities and 3-oxoacyl-CoA thiolase (EC 2.3.1.16).7 Despite the apparent similarities in architecture between the β-oxidation systems in peroxisomes and mitochondria, there are a number of important differences between the two systems with regard to the properties of the individual enzymes, cofactor requirements, coupling to energy production etc. Moreover, the peroxisomal and mitochondrial β-oxidation systems have different substrate specificities. Studies by Moser and coworkers for instance have shown that very long chain fatty acids are primarily oxidized in peroxisomes, at least in rat liver.8 That this is also true in man is indicated by the finding of elevated very long chain fatty acid levels in tissues and body fluids from patients suffering from the cerebro-hepato-renal syndrome of Zellweger in which morphologically distinguishable peroxisomes are known to be absent.9 Recent immunoblotting studies have shown that the three peroxisomal β-oxidation enzyme proteins are strongly deficient in liver from Zellweger patients,10-12 which explains the impairment in peroxisomal very long chain fatty acid β-oxidation8,13-16 leading to elevated very long chain fatty acid levels in these patients.

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Authors and Affiliations

  1. Department of Pediatrics, University Hospital Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    R. J. A. Wanders, C. W. T. Van Roermund, M. J. A. Van Wijland & R. B. H. Schutgens

  2. Laboratory of Biochemistry, University of Utrecht, Padualaan 8, 3584 CH, Utrecht, The Netherlands

    H. Van Den Bosch

  3. Laboratory of Biochemistry, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands

    A. W. Schram & J. M. Tager

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  1. R. J. A. Wanders
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  4. R. B. H. Schutgens
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Editors and Affiliations

  1. Paul Sabatier University, Toulouse, France

    Robert Salvayre  & Louis Douste-Blazy  & 

  2. Hebrew University—Hadassah School of Medicine, Jerusalem, Israel

    Shimon Gatt

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© 1988 Plenum Press, New York

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Wanders, R.J.A. et al. (1988). Identification of the Enzymic Defect in X-Linked Adrenoleukodystrophy: Oxidation of Very Long Chain Fatty Acids is Deficient Due to an Impaired Ability of Peroxisomes to Activate Very Long Chain Fatty Acids. In: Salvayre, R., Douste-Blazy, L., Gatt, S. (eds) Lipid Storage Disorders. NATO ASI Series, vol 150. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1029-7_49

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  • DOI: https://doi.org/10.1007/978-1-4613-1029-7_49

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-8300-3

  • Online ISBN: 978-1-4613-1029-7

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