Source:http://linkedlifedata.com/resource/pubmed/id/18182499
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2008-6-3
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pubmed:abstractText |
Very-long-chain fatty acids (VLCFAs) have long been known to be degraded exclusively in peroxisomes via beta-oxidation. A defect in peroxisomal beta-oxidation results in elevated levels of VLCFAs and is associated with the most frequent inherited disorder of the central nervous system white matter, X-linked adrenoleukodystrophy. Recently, we demonstrated that VLCFAs can also undergo omega-oxidation, which may provide an alternative route for the breakdown of VLCFAs. The omega-oxidation of VLCFA is initiated by CYP4F2 and CYP4F3B, which produce omega-hydroxy-VLCFAs. In this article, we characterized the enzymes involved in the formation of very-long-chain dicarboxylic acids from omega-hydroxy-VLCFAs. We demonstrate that very-long-chain dicarboxylic acids are produced via two independent pathways. The first is mediated by an as yet unidentified, microsomal NAD(+)-dependent alcohol dehydrogenase and fatty aldehyde dehydrogenase, which is encoded by the ALDH3A2 gene and is deficient in patients with Sjögren-Larsson syndrome. The second pathway involves the NADPH-dependent hydroxylation of omega-hydroxy-VLCFAs by CYP4F2, CYP4F3B, or CYP4F3A. Enzyme kinetic studies show that oxidation of omega-hydroxy-VLCFAs occurs predominantly via the NAD(+)-dependent route. Overall, our data demonstrate that in humans all enzymes are present for the complete conversion of VLCFAs to their corresponding very-long-chain dicarboxylic acids.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Aldehyde Oxidoreductases,
http://linkedlifedata.com/resource/pubmed/chemical/CYP4F2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CYP4F3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Dicarboxylic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids,
http://linkedlifedata.com/resource/pubmed/chemical/NAD,
http://linkedlifedata.com/resource/pubmed/chemical/long-chain-aldehyde dehydrogenase
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1530-6860
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
22
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2064-71
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pubmed:meshHeading |
pubmed-meshheading:18182499-Adrenoleukodystrophy,
pubmed-meshheading:18182499-Aldehyde Oxidoreductases,
pubmed-meshheading:18182499-Cytochrome P-450 Enzyme System,
pubmed-meshheading:18182499-Dicarboxylic Acids,
pubmed-meshheading:18182499-Fatty Acids,
pubmed-meshheading:18182499-Humans,
pubmed-meshheading:18182499-Lipid Metabolism,
pubmed-meshheading:18182499-Metabolic Networks and Pathways,
pubmed-meshheading:18182499-NAD,
pubmed-meshheading:18182499-Oxidation-Reduction
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pubmed:year |
2008
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pubmed:articleTitle |
Characterization of the human omega-oxidation pathway for omega-hydroxy-very-long-chain fatty acids.
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pubmed:affiliation |
Academic Medical Center, University of Amsterdam, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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