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Role of very‐long‐chain acyl–coenzyme A synthetase in X‐linked adrenoleukodystrophy
Author(s) -
Steinberg Steven J.,
Kemp Stephan,
Braiterman Lelita T.,
Watkins Paul A.
Publication year - 1999
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/1531-8249(199909)46:3<409::aid-ana18>3.0.co;2-9
Subject(s) - adrenoleukodystrophy , peroxisome , biochemistry , atp binding cassette transporter , coenzyme a , biology , peroxisomal disorder , phytanic acid , chemistry , enzyme , gene , transporter , reductase
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.