| The acyl-CoA synthetase "bubblegum" (lipidosin): further characterization and role in neuronal fatty acid beta-oxidation.. | |
| | |
MedLine Citation:
|
PMID: 12975357 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Acyl-CoA synthetases play a pivotal role in fatty acid metabolism, providing activated substrates for fatty acid catabolic and anabolic pathways. Acyl-CoA synthetases comprise numerous proteins with diverse substrate specificities, tissue expression patterns, and subcellular localizations, suggesting that each enzyme directs fatty acids toward a specific metabolic fate. We reported that hBG1, the human homolog of the acyl-CoA synthetase mutated in the Drosophila mutant "bubblegum," belongs to a previously unidentified enzyme family and is capable of activating both long- and very long-chain fatty acid substrates. We now report that when overexpressed, hBG1 can activate diverse saturated, monosaturated, and polyunsaturated fatty acids. Using in situ hybridization and immunohistochemistry, we detected expression of mBG1, the mouse homolog of hBG1, in cerebral cortical and cerebellar neurons and in steroidogenic cells of the adrenal gland, testis, and ovary. The expression pattern and ability of BG1 to activate very long-chain fatty acids implicates this enzyme in the pathogenesis of X-linked adrenoleukodystrophy. In neuron-derived Neuro2a cells, mBG1 co-sedimented with mitochondria and was found in small vesicular structures located in close proximity to mitochondria. RNA interference was used to decrease mBG1 expression in Neuro2a cells and led to a 30-35% decrease in activation and beta-oxidation of the long-chain fatty acid, palmitate. These results suggest that in Neuro2a cells, mBG1-activated long-chain fatty acids are directed toward mitochondrial degradation. mBG1 appears to play a minor role in very long-chain fatty acid activation in these cells, indicating that other acyl-CoA synthetases are necessary for very long-chain fatty acid metabolism in Neuro2a cells. |
| | |
Authors:
|
Zhengtong Pei; Nadia A Oey; Maartje M Zuidervaart; Zhenzhen Jia; Yuanyuan Li; Steven J Steinberg; Kirby D Smith; Paul A Watkins |
Related Documents
:
|
10542197 - The biotin domain peptide from the biotin carboxyl carrier protein of escherichia coli ... 2187537 - An update of the enzymology and regulation of sphingomyelin metabolism. 3517877 - Protein fatty acid acylation: enzymatic synthesis of an n-myristoylglycyl peptide. 20036447 - Antioxidant and antiviral activities of silybin fatty acid conjugates. 22366607 - Combined biomimetic and inorganic acids hydrolysis of hemicellulose in miscanthus for b... 3791037 - Bile salt related secretion of acid phosphatase in rat bile. |
Publication Detail:
|
Type: Journal Article; Research Support, U.S. Gov't, P.H.S. Date: 2003-09-15 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: 278 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2003 Nov |
Date Detail:
|
Created Date: 2003-11-17 Completed Date: 2004-02-03 Revised Date: 2007-11-14 |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
|
Languages: eng Pagination: 47070-8 Citation Subset: IM |
Affiliation:
|
Kennedy Krieger Institute, Johns Hopkins University School of Medicine, 707 N. Broadway, Baltimore, MD 21205, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adrenoleukodystrophy
/
etiology Animals COS Cells Coenzyme A Ligases / genetics, physiology* DNA, Complementary Fatty Acids / metabolism* Humans Mice Mice, Inbred Strains Microscopy, Fluorescence Mitochondria / enzymology, ultrastructure Neurons / enzymology*, ultrastructure Oxidation-Reduction RNA, Messenger / analysis, metabolism Subcellular Fractions Substrate Specificity Tissue Distribution Transfection |
| Grant Support | |
ID/Acronym/Agency:
|
HD 10982/HD/NICHD NIH HHS; HD 24061/HD/NICHD NIH HHS; NS 37355/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/DNA, Complementary; 0/Fatty Acids; 0/RNA, Messenger; EC 6.2.1.-/Coenzyme A Ligases; EC 6.2.1.-/lipidosin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Association of TAG-1 with Caspr2 is essential for the molecular organization of juxtaparanodal regio...
Next Document: Cleavage of the ADAMTS13 propeptide is not required for protease activity.