Characterization of four mammalian 3-hydroxyacyl-CoA dehydratases involved in very long-chain fatty acid synthesis.
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.
Ikeda
Mika
M
Laboratory of Biomembrane and Biofunctional Chemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
Kanao
Yuki
Y
Yamanaka
Masao
M
Sakuraba
Hiroko
H
Mizutani
Yukiko
Y
Igarashi
Yasuyuki
Y
Kihara
Akio
A
D000123:Acetyltransferases / Q000378:metabolism; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000201:enzymology; D000081031:Fatty Acid Elongases; D005227:Fatty Acids / Q000096:biosynthesis* / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D006836:Hydro-Lyases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D014018:Tissue Distribution
C000630949:ELOVL1 protein, human; D005227:Fatty Acids; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases; D006836:Hydro-Lyases; C529568:Phs1 protein, S cerevisiae