TY - JOUR
T1 - Role of very-long-chain acyl-coenzyme A synthetase in X-linked adrenoleukodystrophy
AU - Steinberg, Steven J.
AU - Kemp, Stephan
AU - Braiterman, Lelita T.
AU - Watkins, Paul A.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
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U2 - 10.1002/1531-8249(199909)46:3<409::AID-ANA18>3.0.CO;2-9
DO - 10.1002/1531-8249(199909)46:3<409::AID-ANA18>3.0.CO;2-9
M3 - Article
C2 - 10482273
AN - SCOPUS:0032869224
SN - 0364-5134
VL - 46
SP - 409
EP - 412
JO - Annals of neurology
JF - Annals of neurology
IS - 3
ER -