Mouse very long-chain acyl-CoA synthetase in X-linked adrenoleukodystrophy.

Ann K. Heinzer, Stephan Kemp, Jyh Feng Lu, Paul A Watkins, Kirby D. Smith

Research output: Contribution to journalArticle

Abstract

X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder characterized by accumulation of very long-chain fatty acids (VLCFA). This accumulation has been attributed to decreased VLCFA beta-oxidation and peroxisomal very long-chain acyl-CoA synthetase (VLCS) activity. The X-ALD gene, ABCD1, encodes a peroxisomal membrane ATP binding cassette transporter, ALDP, that is hypothesized to affect VLCS activity in peroxisomes by direct interaction with the VLCS enzyme. Recently, a VLCS gene that encodes a protein with significant sequence identity to known rat and human peroxisomal VLCS protein has been identified in mice. We find that the mouse VLCS gene (Vlcs) encodes an enzyme (Vlcs) with VLCS activity that localizes to peroxisomes and is expressed in X-ALD target tissues. We show that the expression of Vlcs in the peroxisomes of X-ALD mouse fibroblasts improves VLCFA beta-oxidation in these cells, implying a role for this enzyme in the biochemical abnormality of X-ALD. X-ALD mice, which accumulate VLCFA in tissues, show no change in the expression of Vlcs, the subcellular localization of Vlcs, or general peroxisomal VLCS activity. These observations imply that ALDP is not necessary for the proper expression or localization of Vlcs protein, and the control of VLCFA levels does not depend on the direct interaction of Vlcs and ALDP.

Original languageEnglish (US)
Pages (from-to)28765-28773
Number of pages9
JournalJournal of Biological Chemistry
Volume277
Issue number32
StatePublished - Aug 9 2002

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Adrenoleukodystrophy
Fatty Acids
Peroxisomes
Genes
Enzymes
Tissue
Oxidation
X-Linked Genes
Proteins
ATP-Binding Cassette Transporters
long-chain-fatty-acid-CoA ligase
Fibroblasts
Neurodegenerative Diseases
Rats
Membranes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Mouse very long-chain acyl-CoA synthetase in X-linked adrenoleukodystrophy. / Heinzer, Ann K.; Kemp, Stephan; Lu, Jyh Feng; Watkins, Paul A; Smith, Kirby D.

In: Journal of Biological Chemistry, Vol. 277, No. 32, 09.08.2002, p. 28765-28773.

Research output: Contribution to journalArticle

Heinzer, Ann K. ; Kemp, Stephan ; Lu, Jyh Feng ; Watkins, Paul A ; Smith, Kirby D. / Mouse very long-chain acyl-CoA synthetase in X-linked adrenoleukodystrophy. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 32. pp. 28765-28773.
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