Peroxisomal β-oxidation in X-linked adrenoleukodystrophy
نویسندگان
چکیده
Background: ABCD1 is a peroxisomal ABC transporter whose dysfunction causes X-linked adrenoleukodystrophy (X-ALD). Results: β-Oxidation of C26:0 as well as C22:0 acyl-CoA esters is impaired in X-ALD. ABCD3 accounts for residual β-oxidation activity in XALD fibroblasts. Conclusion: ABCD1 mediates very long-chain acyl-CoA ester β-oxidation without need for additional re-esterification by an acyl-CoA synthetase. Significance: Proof of deficient acyl-CoA ester βoxidation in X-ALD.
منابع مشابه
Peroxisomal fatty acid uptake mechanism in Saccharomyces cerevisiae.
Peroxisomes play a major role in human cellular lipid metabolism, including fatty acid β-oxidation. The most frequent peroxisomal disorder is X-linked adrenoleukodystrophy, which is caused by mutations in ABCD1. The biochemical hallmark of X-linked adrenoleukodystrophy is the accumulation of very long chain fatty acids (VLCFAs) due to impaired peroxisomal β-oxidation. Although this suggests a r...
متن کاملRole of ALDP (ABCD1) and mitochondria in X-linked adrenoleukodystrophy.
Peroxisomal disorders have been associated with malfunction of peroxisomal metabolic pathways, but the pathogenesis of these disorders is largely unknown. X-linked adrenoleukodystrophy (X-ALD) is associated with elevated levels of very-long-chain fatty acids (VLCFA; C(>22:0)) that have been attributed to reduced peroxisomal VLCFA beta-oxidation activity. Previously, our laboratory and others ha...
متن کاملMonitoring of very long-chain fatty acids levels in X-linked adrenoleukodystrophy, treated with haematopoietic stem cell transplantation and Lorenzo's Oil.
X-linked adrenoleukodystrophy is a rare, neurodegenerative peroxisomal disorder connected with mutation in the ABCD1 gene, causing impairment of the peroxisomal β-oxidation process and in consequence, accumulation of very long-chain fatty acids (VLCFA) in blood and tissues. In this study we present serum very long-chain fatty acids levels during clinical course in an X-linked adrenoleukodystrop...
متن کاملX-linked adrenoleukodystrophy: very long-chain fatty acid metabolism is severely impaired in monocytes but not in lymphocytes
X-linked adrenoleukodystrophy (X-ALD) is a fatal neurodegenerative disease caused by mutations in the ABCD1 gene, encoding a member of the peroxisomal ABC transporter family. The ABCD1 protein transports CoA-activated very long-chain fatty acids (VLCFAs) into peroxisomes for degradation via β-oxidation. In the severest form, X-ALD patients suffer from inflammatory demyelination of the brain. As...
متن کاملA very long-chain acyl-CoA synthetase-deficient mouse and its relevance to X-linked adrenoleukodystrophy.
X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative and endocrine disorder resulting from mutations in ABCD1 which encodes a peroxisomal membrane protein in the ATP binding cassette superfamily. The biochemical signature of X-ALD is increased levels of saturated very long-chain fatty acids (VLCFA; carbon chains of 22 or more) in tissues and plasma that has been associated with decrease...
متن کامل