Biochemical aspects of X-linked adrenoleukodystrophy.
X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. The disease is characterized by the accumulation of very long-chain fatty acids (VLCFA; >C22) in plasma and tissues. X-ALD is caused by mutations in the ABCD1 gene encoding ALDP, an adenosine triphosphate (ATP)-binding-cassette (ABC) transporter located in the peroxisomal membrane. In this paper, we describe the current knowledge on the function of ALDP, its role in peroxisomal VLCFA beta-oxidation and the consequences of a defect in ALDP on VLCFA metabolism. Furthermore, we pay special attention to the role of the VLCFA elongation system in VLCFA homeostasis, with elongation of very long-chain fatty acids like-1 (ELOVL1) as key player, and its relevance to X-ALD.
Kemp
Stephan
S
Academic Medical Center, University of Amsterdam, Laboratory Genetic Metabolic Diseases, Departments of Pediatrics/Emma Children's Hospital and Clinical Chemistry, Amsterdam, the Netherlands. s.kemp@amc.uva.nl
Wanders
Ronald
R
D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000326:Adrenoleukodystrophy / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation
C115572:ABCD1 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; D005227:Fatty Acids