Document Detail


Direct demonstration that the deficient oxidation of very long chain fatty acids in X-linked adrenoleukodystrophy is due to an impaired ability of peroxisomes to activate very long chain fatty acids.
MedLine Citation:
PMID:  3382393     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A method was developed to prepare peroxisome-enriched fractions depleted of microsomes and mitochondria from cultured skin fibroblasts. The method consists of differential centrifugation of a postnuclear supernatant followed by density gradient centrifugation on a discontinuous Metrizamide gradient. The activity of hexacosanoyl-CoA synthetase was subsequently measured in postnuclear supernatants and peroxisome-enriched fractions prepared from cultured skin fibroblasts from control subjects and patients with X-linked adrenoleukodystrophy. Whereas the hexacosanoyl-CoA synthetase activity in postnuclear supernatants of X-linked adrenoleukodystrophy fibroblasts was only slightly decreased (77.8 +/- 4.4% of control (n = 15], enzyme activity was found to be much more markedly reduced in peroxisomal fractions isolated from the mutant fibroblasts (19.6 +/- 6.7% of control (n = 5]. This is a direct demonstration that the defect in X-linked adrenoleukodystrophy is at the level of a deficient ability of peroxisomes to activate very long chain fatty acids, as first suggested by Hashmi et al. [Hashmi, M., Stanley, W. and Singh, I. (1986) FEBS Lett. 86, 247-250].
Authors:
R J Wanders; C W van Roermund; M J van Wijland; R B Schutgens; H van den Bosch; A W Schram; J M Tager
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  153     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  1988 Jun 
Date Detail:
Created Date:  1988-07-22     Completed Date:  1988-07-22     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  618-24     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, University Hospital Amsterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Adrenoleukodystrophy / metabolism*
Catalase / metabolism
Cell Fractionation
Cells, Cultured
Centrifugation, Density Gradient
Diffuse Cerebral Sclerosis of Schilder / metabolism*
Fatty Acid Synthetase Complex / metabolism
Fatty Acids / metabolism*
Humans
Microbodies / metabolism*
Microsomes / metabolism
Mitochondria / metabolism
Skin / enzymology
Chemical
Reg. No./Substance:
0/Fatty Acids; 506-46-7/hexacosanoic acid; EC 1.11.1.6/Catalase; EC 6.-/Fatty Acid Synthetase Complex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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