Ether lipid biosynthesis (WP5275)

Homo sapiens

Ether lipid biosynthesis in humans. Ether lipids (e.g. plasmalogens), are peroxisome-derived glycerophospholipids where the hydrocarbon chain at the sn-1 position of the glycerol backbone is attached by an ether bond (single bond between carbon and oxygen atom). Ether lipids are used to form non-lamellar inverted hexagonal structures in model membranes (indicating they could facilitate membrane fusion processes). Lipid raft microdomains (cholesterol-rich membrane regions involved in cellular signaling) rely on ether lipids for their organization and stability. [PMID:28523433]. The pathway knowledge depicted in this model stems from Robert C. Murphy, who endorsed version r123734. Metabolic conversion missing an identifier from Rhea have been visualized with double line thickness.


Conroy lipids , Denise Slenter , Egon Willighagen , Robert C. Murphy , Alex Pico , and Eric Weitz


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Homo sapiens


Inherited Metabolic Disorders (IMD) Pathways Lipids and LIPID MAPS


Disease Ontology

rhizomelic chondrodysplasia punctata Zellweger syndrome rhizomelic chondrodysplasia punctata type 3 peroxisome biogenesis disorder 1A rhizomelic chondrodysplasia punctata type 5 rhizomelic chondrodysplasia punctata type 1 rhizomelic chondrodysplasia punctata type 2

Pathway Ontology

ether lipid metabolic pathway lipid metabolic pathway Zellweger syndrome pathway classic metabolic pathway


Label Type Compact URI Comment
DG-O Metabolite lipidmaps:LMGL02020000
Acyl-CoA Metabolite lipidmaps:LMFA07050000
Alkyl-DHAP Metabolite lipidmaps:LMGP22020000
Fatty acid Metabolite lipidmaps:LMFA01010000
LPA Metabolite lipidmaps:LMGP10050000
Acyl-DHAP Metabolite lipidmaps:LMGP22010000
Coenzyme A Metabolite chebi:15346
LPA-O Metabolite lipidmaps:LMGP10060000
GalEAG Metabolite lipidmaps:LMGL050200A0
PC-O Metabolite lipidmaps:LMGP01020000
PE-O Metabolite lipidmaps:LMGP02020000
PA-O Metabolite lipidmaps:LMGP10020000
PE-P Metabolite lipidmaps:LMGP02030000 AKA PE-Plasmalogen
Fatty alcohol Metabolite lipidmaps:LMFA05000000
DHAP Metabolite chebi:16108 aka dihydroxyacetone phosphate
Seminolipid Metabolite lipidmaps:LMGL05020000
Acyl-CoA Metabolite lipidmaps:LMFA07050000
Coenzyme A Metabolite chebi:15346
Alkyl-DHAP Metabolite lipidmaps:LMGP22020000
Acyl-CoA Metabolite lipidmaps:LMFA07050000
Fatty acid Metabolite chebi:57560
Fatty alcohol Metabolite lipidmaps:LMFA05000000
Acyl-DHAP Metabolite lipidmaps:LMGP22010000
PexRAP GeneProduct uniprot:Q6IAN0 AKA an acyl/alkyl DHAP reductase; 'identified this gene as dhrs7b and renamed the protein PexRAP (for peroxisomal reductase activating PPARγ)' [PMID:28523433]
ACS GeneProduct eccode: AKA acyl-CoA synthetase; composed of two subunits.
LPIN3 GeneProduct uniprot:Q9BQK8
GNPAT GeneProduct uniprot:O15228 AKA glyceronephosphate O-acyltransferase
PEX1 GeneProduct uniprot:O43933
ARSA GeneProduct uniprot:P15289
PEDS1 GeneProduct uniprot:A5PLL7
LPCAT1 GeneProduct uniprot:Q8NF37
AGPS GeneProduct uniprot:O00116
PEX5L GeneProduct uniprot:Q8IYB4 AKA Pex5 long isoform; 'While both the long and short Pex5 isoforms recognize PTS1-containing proteins, Pex5L is a co-receptor with Pex7 for the import of PTS2-containing proteins, and its loss results only in impaired PTS2-tagged protein import' [PMID:28523433]. AGPS contains a PTS2 domain (type-2 peroxisomal targeting signal). [PMID:31751594]
PEX7 GeneProduct uniprot:O00628 AKA peroxisomal import receptor for proteins, including AGPS [PMID:28523433]
GAL3ST1 GeneProduct uniprot:Q99999 EC
LPIN1 GeneProduct uniprot:Q14693
UGT8 GeneProduct uniprot:Q16880
LPIN2 GeneProduct uniprot:Q92539
CEPT1 GeneProduct uniprot:Q9Y6K0
FAR1 GeneProduct uniprot:Q8WVX9 AKA fatty acyl-CoA reductase.
FAR2 GeneProduct uniprot:Q96K12 AKA fatty acyl-CoA reductase.
AGPS GeneProduct uniprot:O00116
PEX7 GeneProduct uniprot:O00628 AKA peroxisomal import receptor for proteins, including AGPS [PMID:28523433]
PEX3 GeneProduct uniprot:P56589
PEX16 GeneProduct uniprot:Q9Y5Y5
PEX19 GeneProduct uniprot:P40855
UNIDENTIFIED Protein eccode: Putative EC number as found in RHGEA entry


  1. Deficiency of seminolipid sulphatase activity in brain tissue of metachromatic leucodystrophy. Yamaguchi S, Aoki K, Handa S, Yamakawa T. J Neurochem. 1975 May;24(5):1087–9. PubMed Europe PMC Scholia
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  7. Characterization of the human LPIN1-encoded phosphatidate phosphatase isoforms. Han GS, Carman GM. J Biol Chem. 2010 May 7;285(19):14628–38. PubMed Europe PMC Scholia
  8. Inhibiting adipose tissue lipogenesis reprograms thermogenesis and PPARγ activation to decrease diet-induced obesity. Lodhi IJ, Yin L, Jensen-Urstad APL, Funai K, Coleman T, Baird JH, et al. Cell Metab. 2012 Aug 8;16(2):189–201. PubMed Europe PMC Scholia
  9. Structural and functional roles of ether lipids. Dean JM, Lodhi IJ. Protein Cell. 2018 Feb;9(2):196–206. PubMed Europe PMC Scholia
  10. The TMEM189 gene encodes plasmanylethanolamine desaturase which introduces the characteristic vinyl ether double bond into plasmalogens. Werner ER, Keller MA, Sailer S, Lackner K, Koch J, Hermann M, et al. Proc Natl Acad Sci U S A. 2020 Apr 7;117(14):7792–8. PubMed Europe PMC Scholia