X-linked adrenoleukodystrophy: Identification of the primary defect at the level of a deficient peroxisomal very long chain fatty acyl-CoA synthetase using a newly developed method for the isolation of peroxisomes from skin fibroblasts

摘要: Several types of adrenoleukodystrophy (ALD) differing in age onset, mode inheritance and clinical presentation have been described the literature. The X-linked form adrenoleukodystrophy, which is most common, characterized by demyelination, adrenal sufficiency accumulation very long chain fatty acids, particularly hexacosanoic acid (C26:0), tissues body fluids (Moser et al., 1984). It now generally accepted that acids ALD caused their impaired degradation via peroxisomal β-oxidation system as first shown Singh co-workers 1981 (see also Rizzo 1984; Tsuji 1985). Recent studies deficient oxidation X- linked not a deficiency one enzymes (acyl-CoA oxidase, bifunctional protein with enoyl-CoA hydratase 3-hydroxyacyl-CoA dehydrogenase activities 3-oxoacyl-CoA thiolase) since all three enzyme proteins were only found to be immunologically present immunoblotting (Wanders 1987) but functionally active (Hashmi 1986; Wanders 1987). latter finding led Hashmi suggest defect at level activation CoA-esters. However, measurement this activity fibroblasts using tetracosanoic (C24:0) (C26:0) substrates revealed partial (about 25%) acyl-CoA synthetase 1987a).