Linked Life Data

10640429

Source:http://linkedlifedata.com/resource/pubmed/id/10640429

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-4-5
pubmed:abstractText
X-adrenoleukodystrophy (X-ALD) is a demyelinating disorder characterized by the accumulation of saturated very-long-chain (VLC) fatty acids (>C(22:0)) due to the impaired activity of VLC acyl-CoA synthetase (VLCAS). The gene responsible for X-ALD was found to code for a peroxisomal integral membrane protein (ALDP) that belongs to the ATP binding cassette superfamily of transporters. To understand the function of ALDP and how ALDP and VLCAS interrelate in the peroxisomal beta-oxidation of VLC fatty acids we investigated the peroxisomal topology of VLCAS protein. Antibodies raised against a peptide toward the C-terminus of VLCAS as well as against the N-terminus were used to define the intraperoxisomal localization and orientation of VLCAS in peroxisomes. Indirect immunofluorescent and electron microscopic studies show that peroxisomal VLCAS is localized on the matrix side. This finding was supported by protease protection assays and Western blot analysis of isolated peroxisomes. To further address the membrane topology of VLCAS, Western blot analysis of total membranes or integral membranes prepared from microsomes and peroxisomes indicates that VLCAS is a peripheral membrane-associated protein in peroxisomes, but an integral membrane in microsomes. Moreover, peroxisomes isolated from cultured skin fibroblasts from X-ALD patients with a mutation as well as a deletion in ALDP showed a normal amount of VLCAS. The consequence of VLCAS being localized to the luminal side of peroxisomes suggests that ALDP may be involved in stabilizing VLCAS activity, possibly through protein-protein interactions, and that loss or alterations in these interactions may account for the observed loss of peroxisomal VLCAS activity in X-ALD.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0014-4827
pubmed:author
pubmed:copyrightInfo
Copyright 2000 Academic Press.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
254
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
309-20
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10640429-Adrenoleukodystrophy, pubmed-meshheading:10640429-Amino Acid Sequence, pubmed-meshheading:10640429-Animals, pubmed-meshheading:10640429-Antibodies, pubmed-meshheading:10640429-Cell Fractionation, pubmed-meshheading:10640429-Cell Line, pubmed-meshheading:10640429-Cells, Cultured, pubmed-meshheading:10640429-Coenzyme A Ligases, pubmed-meshheading:10640429-Epitopes, pubmed-meshheading:10640429-Fibroblasts, pubmed-meshheading:10640429-Humans, pubmed-meshheading:10640429-Liver, pubmed-meshheading:10640429-Microsomes, Liver, pubmed-meshheading:10640429-Molecular Sequence Data, pubmed-meshheading:10640429-Peptide Fragments, pubmed-meshheading:10640429-Peroxisomes, pubmed-meshheading:10640429-Rats, pubmed-meshheading:10640429-Rats, Sprague-Dawley, pubmed-meshheading:10640429-Repressor Proteins, pubmed-meshheading:10640429-Saccharomyces cerevisiae Proteins, pubmed-meshheading:10640429-Skin, pubmed-meshheading:10640429-X Chromosome
pubmed:year
2000
pubmed:articleTitle
Intraperoxisomal localization of very-long-chain fatty acyl-CoA synthetase: implication in X-adrenoleukodystrophy.
pubmed:affiliation
Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.