Characterization of four mammalian 3-hydroxyacyl-CoA dehydratases involved in very long-chain fatty acid synthesis

FEBS Lett. 2008 Jul 9;582(16):2435-40. doi: 10.1016/j.febslet.2008.06.007. Epub 2008 Jun 11.


Very long-chain fatty acids are produced through a four-step cycle. However, the 3-hydroxyacyl-CoA dehydratase catalyzing the third step in mammals has remained unidentified. Mammals have four candidates, HACD1-4, based on sequence similarities to the recently identified yeast Phs1, although HACD3 and HACD4 share relatively weak similarity. We demonstrate that all four of these human proteins are indeed 3-hydroxyacyl-CoA dehydratases, in growth suppression experiments using a PHS1-shut off yeast strain and/or in vitro 3-hydroxypalmitoyl-CoA dehydratase assays. HACD proteins exhibit distinct tissue-expression patterns. We also establish that HACD proteins interact with the condensation enzymes ELOVL1-7, with some preferences.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / metabolism
  • Cell Line
  • Endoplasmic Reticulum / enzymology
  • Fatty Acid Elongases
  • Fatty Acids / biosynthesis*
  • Fatty Acids / chemistry
  • HeLa Cells
  • Humans
  • Hydro-Lyases / metabolism*
  • RNA, Messenger / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Tissue Distribution


  • ELOVL1 protein, human
  • Fatty Acids
  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • Acetyltransferases
  • Fatty Acid Elongases
  • Hydro-Lyases
  • Phs1 protein, S cerevisiae