The Acyl-CoA synthetase "bubblegum" (lipidosin): Further characterization and role in neuronal fatty acid β-oxidation

Zhengtong Pei, Nadia A. Oey, Maartje M. Zuidervaart, Zhenzhen Jia, Yuanyuan Li, Steven J. Steinberg, Kirby D. Smith, Paul A Watkins

Research output: Contribution to journalArticle

Abstract

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 β-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.

Original languageEnglish (US)
Pages (from-to)47070-47078
Number of pages9
JournalJournal of Biological Chemistry
Volume278
Issue number47
DOIs
StatePublished - Nov 21 2003

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Coenzyme A Ligases
Fatty Acids
Oxidation
Mitochondria
Metabolism
Neurons
Enzymes
Mitochondrial Degradation
Substrates
Adrenoleukodystrophy
Chemical activation
lipidosin
Palmitates
Adrenal Glands
Substrate Specificity
RNA Interference
Unsaturated Fatty Acids
Drosophila
In Situ Hybridization
Testis

ASJC Scopus subject areas

  • Biochemistry

Cite this

The Acyl-CoA synthetase "bubblegum" (lipidosin) : Further characterization and role in neuronal fatty acid β-oxidation. / Pei, Zhengtong; Oey, Nadia A.; Zuidervaart, Maartje M.; Jia, Zhenzhen; Li, Yuanyuan; Steinberg, Steven J.; Smith, Kirby D.; Watkins, Paul A.

In: Journal of Biological Chemistry, Vol. 278, No. 47, 21.11.2003, p. 47070-47078.

Research output: Contribution to journalArticle

Pei, Zhengtong ; Oey, Nadia A. ; Zuidervaart, Maartje M. ; Jia, Zhenzhen ; Li, Yuanyuan ; Steinberg, Steven J. ; Smith, Kirby D. ; Watkins, Paul A. / The Acyl-CoA synthetase "bubblegum" (lipidosin) : Further characterization and role in neuronal fatty acid β-oxidation. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 47. pp. 47070-47078.
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