Role of very-long-chain acyl-coenzyme A synthetase in X-linked adrenoleukodystrophy

Steven J. Steinberg, Stephan Kemp, Lelita T. Braiterman, Paul A. Watkins

Research output: Contribution to journalArticle

Abstract

X-linked adrenoleukodystrophy (X-ALD) is characterized biochemically by decreased ability of cells to activate (via very-long-chain acyl-coenzyme A synthetase [VLCS]) and subsequently degrade very-long-chain fatty acids in peroxisomes. It is noteworthy that the gene defective in X-ALD encodes ALDP, a peroxisomal membrane protein unrelated to VLCS. We cloned human VLCS (hVLCS) and found that peroxisomes from X-ALD fibroblasts contained immunoreactive hVLCS, refuting the earlier hypothesis that ALDP is required to anchor VLCS to the peroxisomal membrane. Furthermore, hVLCS was topographically oriented facing the peroxisomal matrix in both control and X- ALD fibroblasts, contradicting the alternative hypothesis that ALDP is required to translocate VLCS into peroxisomes. However, overexpression of both hVLCS and ALDP in X-ALD fibroblasts synergistically increased very-long- chain fatty acid β-oxidation, indicating that these proteins interact functionally.

Original languageEnglish (US)
Pages (from-to)409-412
Number of pages4
JournalAnnals of neurology
Volume46
Issue number3
DOIs
StatePublished - Sep 13 1999

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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