Human very-long-chain Acyl-CoA synthetase: Cloning, topography, and relevance to branched-chain fatty acid metabolism

Steven J. Steinberg, Susan J. Wang, Do G. Kim, Stephanie J. Mihalik, Paul A. Watkins

Research output: Contribution to journalArticle

Abstract

Very-long-chain acyl-CoA synthetases (VLCS) activate very-long-chain fatty acids (VLCFA) containing 22 or more carbons to their CoA derivatives. We cloned the human ortholog (hVLCS) of the gene encoding the rat liver enzyme (rVLCS). Both hVLCS and rVLCS contain 620 amino acids, are expressed primarily in liver and kidney, and have a potential peroxisome targeting signal 1 (-LKL) at their carboxy termini. When expressed in COS-1 cells, hVLCS activated the VLCFA lignoceric acid (C24:0), a long-chain fatty acid (C16:0), and two branched-chain fatty acids, phytanic acid and pristanic acid. Immunofluorescence and immunoblot studies localized hVLCS to both peroxisomes and endoplasmic reticulum. In peroxisomes of HepG2 cells, hVLCS was topographically oriented facing the matrix and not the cytoplasm. This orientation, coupled with the observation that hVLCS activates branched-chain fatty acids, suggests that hVLCS could play a role in the intraperoxisomal reactivation of pristanic acid produced via α-oxidation of phytanic acid.

Original languageEnglish (US)
Pages (from-to)615-621
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume257
Issue number2
DOIs
StatePublished - Apr 13 1999

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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