Source:http://linkedlifedata.com/resource/pubmed/id/10479480
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
1999-10-19
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| pubmed:databankReference | |
| pubmed:abstractText |
Activation of fatty acids, catalyzed by acyl-coenzyme A (acyl-CoA) synthetases, is required for their subsequent metabolism. Peroxisomes and microsomes contain very-long-chain acyl-CoA synthetases (VLCSs) capable of activating fatty acids with a chain length of 22 or more carbons. Decreased peroxisomal VLCS activity is, in part, responsible for the biochemical pathology in X-linked adrenoleukodystrophy (X-ALD), illustrating the importance of VLCSs in cellular fatty acid homeostasis. We previously cloned two human genes encoding proteins homologous to rat peroxisomal VLCS; one (hVLCS) is the human ortholog to the rat VLCS gene and another (hVLCS-H1) encodes a related heart-specific protein. Here, we report the cloning of a third gene (hVLCS-H2) and characterization of its protein product. The hVLCS-H2 gene is located on human chromosome 19 and encodes a 690-amino-acid protein. The amino acid sequence of hVLCS-H2 is 44-45% identical and 67-69% similar to those of both hVLCS and hVLCS-H1. COS-1 cells transiently overexpressing hVLCS-H2 activated the very-long-chain fatty acid lignocerate (C24:0) at a rate >1.5-fold higher than that of nontransfected cells (P < 0.002). The hVLCS-H2-dependent activation of long- and branched-chain fatty acids following transient transfection was less striking. However, hVLCS-H2-dependent acyl-CoA synthetase activity with long- and very-long-chain fatty acid substrates was detected in COS-1 cells stably expressing hVLCS-H2. For all substrates tested (C18:0, C20:0, C24:0, C26:0), the hVLCS-H2 catalyzed activity was significantly increased (P < 0.01 to P < 0.0001). By both Northern analysis and reverse transcription polymerase chain reaction, hVLCS-H2 is expressed primarily in liver. Indirect immunofluorescence of COS-1 cells or human hepatoma-derived HepG2 cells expressing epitope-tagged hVLCS-H2 revealed that the protein was associated with the endoplasmic reticulum but not with peroxisomes. Thus, the primary role of hVLCS-H2 is likely to be in fatty acid elongation or complex lipid synthesis rather than in degradation.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Coenzyme A Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/FAA2 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/long-chain-fatty-acid-CoA ligase
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
1096-7192
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright 1999 Academic Press.
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| pubmed:issnType |
Print
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| pubmed:volume |
68
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
32-42
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:10479480-Amino Acid Sequence,
pubmed-meshheading:10479480-Animals,
pubmed-meshheading:10479480-Base Sequence,
pubmed-meshheading:10479480-Blotting, Northern,
pubmed-meshheading:10479480-COS Cells,
pubmed-meshheading:10479480-Chromosome Mapping,
pubmed-meshheading:10479480-Chromosomes, Human, Pair 19,
pubmed-meshheading:10479480-Cloning, Molecular,
pubmed-meshheading:10479480-Coenzyme A Ligases,
pubmed-meshheading:10479480-DNA, Complementary,
pubmed-meshheading:10479480-Endoplasmic Reticulum,
pubmed-meshheading:10479480-Fluorescent Antibody Technique, Indirect,
pubmed-meshheading:10479480-Humans,
pubmed-meshheading:10479480-Isoenzymes,
pubmed-meshheading:10479480-Liver,
pubmed-meshheading:10479480-Microbodies,
pubmed-meshheading:10479480-Molecular Sequence Data,
pubmed-meshheading:10479480-RNA,
pubmed-meshheading:10479480-Repressor Proteins,
pubmed-meshheading:10479480-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:10479480-Sequence Analysis, DNA,
pubmed-meshheading:10479480-Tissue Distribution,
pubmed-meshheading:10479480-Tumor Cells, Cultured
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| pubmed:year |
1999
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| pubmed:articleTitle |
Human liver-specific very-long-chain acyl-coenzyme A synthetase: cDNA cloning and characterization of a second enzymatically active protein.
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| pubmed:affiliation |
Kennedy Krieger Institute and Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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