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. dff Putative EC number as found in RHGEA entry https://www.rhea-db.org/rhea/36175 AKA an acyl/alkyl DHAP reductase; "identified this gene as dhrs7b and renamed the protein PexRAP (for peroxisomal reductase activating PPARγ)" [PMID:28523433] cae AKA acyl-CoA synthetase; composed of two subunits. AKA glyceronephosphate O-acyltransferase AKA PE-Plasmalogen 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] AKA peroxisomal import receptor for proteins, including AGPS [PMID:28523433] EC 2.8.2.11 aka dihydroxyacetone phosphate AKA fatty acyl-CoA reductase. AKA fatty acyl-CoA reductase. AKA peroxisomal import receptor for proteins, including AGPS [PMID:28523433] c63 a6e dff e2c Rhea ID matching based on EC-code overlap. ceb dff dff b2a Reaction does not seem to be represented in Rhea, nor linked from UniProt to Rhea. b29 c01 bd8 bd8 "fatty acids are first activated to fatty acyl-CoAs by an acyl-CoA synthetase (ACS) associated with the peroxisomal membrane." [PMID:28523433] dff dff dff dff dff dff AKA Rhizomelic chondrodysplasia punctata, type 1 AKA Rhizomelic chondrodysplasia punctata, type 2 AKA Rhizomelic chondrodysplasia punctata, type 3 AKA Rhizomelic chondrodysplasia punctata, type 4; PEROXISOMAL FATTY ACYL-CoA REDUCTASE 1 DISORDER AKA Rhizomelic chondrodysplasia punctata, type 5 AKA PEROXISOME BIOGENESIS DISORDER 1A AKA PEROXISOME BIOGENESIS DISORDER 1B; infantile Refsum disease dff dff rhizomelic chondrodysplasia punctata DOID:2580 Disease Zellweger syndrome DOID:905 Disease rhizomelic chondrodysplasia punctata type 3 DOID:0110853 Disease peroxisome biogenesis disorder 1A DOID:0080476 Disease ether lipid metabolic pathway PW:0001138 Pathway Ontology lipid metabolic pathway PW:0000010 Pathway Ontology 32209662 PubMed The<i>TMEM189</i>gene encodes plasmanylethanolamine desaturase which introduces the characteristic vinyl ether double bond into plasmalogens. Proc Natl Acad Sci U S A 2020 Werner ER Keller MA Sailer S Lackner K Koch J Hermann M Coassin S Golderer G Werner-Felmayer G Zoeller RA Hulo N Berger J Watschinger K 10801776 PubMed Requirement of seminolipid in spermatogenesis revealed by UDP-galactose: Ceramide galactosyltransferase-deficient mice. J Biol Chem 2000 Fujimoto H Tadano-Aritomi K Tokumasu A Ito K Hikita T Suzuki K Ishizuka I rhizomelic chondrodysplasia punctata type 5 DOID:0110854 Disease 15687349 PubMed Role of dihydroxyacetonephosphate acyltransferase in the biosynthesis of plasmalogens and nonether glycerolipids. J Lipid Res 2005 Liu D Nagan N Just WW Rodemer C Thai TP Zoeller RA rhizomelic chondrodysplasia punctata type 1 DOID:0110851 Disease 22863804 PubMed Inhibiting adipose tissue lipogenesis reprograms thermogenesis and PPARγ activation to decrease diet-induced obesity Cell Metab. 2012 Irfan J Lodhi Li Yin Anne P L Jensen-Urstad Katsuhiko Funai Trey Coleman John H Baird Meral K El Ramahi Babak Razani Haowei Song Fong Fu-Hsu John Turk Clay F Semenkovich 10191259 PubMed Cloning and expression of a human choline/ethanolaminephosphotransferase: synthesis of phosphatidylcholine and phosphatidylethanolamine. Biochem J 1999 Henneberry AL McMaster CR 237979 PubMed Deficiency of seminolipid sulphatase activity in brain tissue of metachromatic leucodystrophy. J Neurochem 1975 Yamaguchi S Aoki K Handa S Yamakawa T 28523433 PubMed Structural and functional roles of ether lipids Protein Cell. 2018 28523433 PubMed Structural and functional roles of ether lipids Protein Cell. 2018 John M. Dean Irfan J. Lodhi 20231281 PubMed Characterization of the human LPIN1-encoded phosphatidate phosphatase isoforms. J Biol Chem 2010 Han GS Carman GM Zellweger syndrome pathway PW:0001415 Pathway Ontology classic metabolic pathway PW:0000002 Pathway Ontology rhizomelic chondrodysplasia punctata type 2 DOID:0110852 Disease 8830034 PubMed Purification and characterization of 3'-phosphoadenosine-5'-phosphosulfate:GalCer sulfotransferase from human renal cancer cells. J Biochem 1996 Honke K Yamane M Ishii A Kobayashi T Makita A 8399344 PubMed Ether lipid synthesis: purification and identification of alkyl dihydroxyacetone phosphate synthase from guinea-pig liver. Biochim Biophys Acta 1993 Zomer AW de Weerd WF Langeveld J van den Bosch H