title: Accumulation of long-chain bases in yeast promotes their conversion to a long-chain base vinyl ether.
abstract: Long-chain bases (LCBs) are the precursors to ceramide and sphingolipids in eukaryotic cells. They are formed by the action of serine palmitoyl-CoA transferase (SPT), a complex of integral membrane proteins located in the endoplasmic reticulum. SPT activity is negatively regulated by Orm proteins to prevent the toxic overaccumulation of LCBs. Here we show that overaccumulation of LCBs in yeast results in their conversion to a hitherto undescribed LCB derivative, an LCB vinyl ether. The LCB vinyl ether is predominantly formed from phytosphingosine (PHS) as revealed by conversion of odd chain length tracers C17-dihydrosphingosine and C17-PHS into the corresponding LCB vinyl ether derivative. PHS vinyl ether formation depends on ongoing acetyl-CoA synthesis, and its levels are elevated when the LCB degradative pathway is blocked by deletion of the major LCB kinase, LCB4, or the LCB phosphate lyase, DPL1. PHS vinyl ether formation thus appears to constitute a shunt for the LCB phosphate- and lyase-dependent degradation of LCBs. Consistent with a role of PHS vinyl ether formation in LCB detoxification, the lipid is efficiently exported from the cells.
authors: Department of Biology, University of Fribourg, 1700 Fribourg, Switzerland.
authors: Fernando
authors: F
authors: Martínez-Montañés
authors: Department of Biology, University of Fribourg, 1700 Fribourg, Switzerland.
authors: Museer A
authors: MA
authors: Lone
authors: Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110.
authors: Fong-Fu
authors: FF
authors: Hsu
authors: Department of Biology, University of Fribourg, 1700 Fribourg, Switzerland roger.schneiter@unifr.ch.
authors: Roger
authors: R
authors: Schneiter
mesh_terms: D000105:Acetyl Coenzyme A / Q000096:biosynthesis / Q000737:chemistry; D002518:Ceramides / Q000737:chemistry / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism; D010710:Phosphates / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism; D051102:Serine C-Palmitoyltransferase / Q000737:chemistry / Q000378:metabolism*; D013107:Sphingolipids / Q000737:chemistry / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D014753:Vinyl Compounds / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002518:Ceramides; C548539:Orm1 protein, S cerevisiae; D010710:Phosphates; D029701:Saccharomyces cerevisiae Proteins; D013107:Sphingolipids; D014753:Vinyl Compounds; C100195:vinyl ether; D000105:Acetyl Coenzyme A; D051102:Serine C-Palmitoyltransferase; C012491:phytosphingosine; D013110:Sphingosine
keywords: Saccharomyces cerevisiae; ceramide; mass spectrometry; sphingolipids