title: Role of very-long-chain acyl-coenzyme A synthetase in X-linked adrenoleukodystrophy.
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 beta-oxidation, indicating that these proteins interact functionally.
authors.affiliation: Kennedy Krieger Institute, Baltimore, MD 21205, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Steinberg
authors.forename: S
authors.initials: S
authors.lastname: Kemp
authors.forename: L T
authors.initials: LT
authors.lastname: Braiterman
authors.forename: P A
authors.initials: PA
authors.lastname: Watkins
mesh_terms: D000326:Adrenoleukodystrophy / Q000235:genetics*; D002460:Cell Line; D003066:Coenzyme A Ligases / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014960:X Chromosome / Q000235:genetics*; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
chemical_list: D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase