Ether lipid biosynthesis (Homo sapiens)

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Description

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.

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Ontology Terms

 

Bibliography

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  1. Henneberry AL, McMaster CR; ''Cloning and expression of a human choline/ethanolaminephosphotransferase: synthesis of phosphatidylcholine and phosphatidylethanolamine.''; Biochem J, 1999 PubMed Europe PMC Scholia
  2. Han GS, Carman GM; ''Characterization of the human LPIN1-encoded phosphatidate phosphatase isoforms.''; J Biol Chem, 2010 PubMed Europe PMC Scholia
  3. 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; ''Inhibiting adipose tissue lipogenesis reprograms thermogenesis and PPARγ activation to decrease diet-induced obesity''; Cell Metab., 2012 PubMed Europe PMC Scholia
  4. Liu D, Nagan N, Just WW, Rodemer C, Thai TP, Zoeller RA; ''Role of dihydroxyacetonephosphate acyltransferase in the biosynthesis of plasmalogens and nonether glycerolipids.''; J Lipid Res, 2005 PubMed Europe PMC Scholia
  5. Fujimoto H, Tadano-Aritomi K, Tokumasu A, Ito K, Hikita T, Suzuki K, Ishizuka I; ''Requirement of seminolipid in spermatogenesis revealed by UDP-galactose: Ceramide galactosyltransferase-deficient mice.''; J Biol Chem, 2000 PubMed Europe PMC Scholia
  6. John M. Dean, Irfan J. Lodhi; ''Structural and functional roles of ether lipids''; Protein Cell., 2018 PubMed Europe PMC Scholia
  7. Ofman R, Hettema EH, Hogenhout EM, Caruso U, Muijsers AO, Wanders RJ; ''Acyl-CoA:dihydroxyacetonephosphate acyltransferase: cloning of the human cDNA and resolution of the molecular basis in rhizomelic chondrodysplasia punctata type 2.''; Hum Mol Genet, 1998 PubMed Europe PMC Scholia
  8. Cheng JB, Russell DW; ''Mammalian wax biosynthesis. I. Identification of two fatty acyl-Coenzyme A reductases with different substrate specificities and tissue distributions.''; J Biol Chem, 2004 PubMed Europe PMC Scholia
  9. 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; ''TheTMEM189gene encodes plasmanylethanolamine desaturase which introduces the characteristic vinyl ether double bond into plasmalogens.''; Proc Natl Acad Sci U S A, 2020 PubMed Europe PMC Scholia
  10. Ferdinandusse S, McWalter K, Te Brinke H, IJlst L, Mooijer PM, Ruiter JPN, van Lint AEM, Pras-Raves M, Wever E, Millan F, Guillen Sacoto MJ, Begtrup A, Tarnopolsky M, Brady L, Ladda RL, Sell SL, Nowak CB, Douglas J, Tian C, Ulm E, Perlman S, Drack AV, Chong K, Martin N, Brault J, Brokamp E, Toro C, Gahl WA, Macnamara EF, Wolfe L, Waisfisz Q, Zwijnenburg PJG, Ziegler A, Barth M, Smith R, Ellingwood S, Gaebler-Spira D, Bakhtiari S, Kruer MC, van Kampen AHC, Wanders RJA, Waterham HR, Cassiman D, Vaz FM; ''An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids.''; Genet Med, 2021 PubMed Europe PMC Scholia
  11. Thai TP, Heid H, Rackwitz HR, Hunziker A, Gorgas K, Just WW; ''Ether lipid biosynthesis: isolation and molecular characterization of human dihydroxyacetonephosphate acyltransferase.''; FEBS Lett, 1997 PubMed Europe PMC Scholia
  12. Yamaguchi S, Aoki K, Handa S, Yamakawa T; ''Deficiency of seminolipid sulphatase activity in brain tissue of metachromatic leucodystrophy.''; J Neurochem, 1975 PubMed Europe PMC Scholia
  13. Honke K, Yamane M, Ishii A, Kobayashi T, Makita A; ''Purification and characterization of 3'-phosphoadenosine-5'-phosphosulfate:GalCer sulfotransferase from human renal cancer cells.''; J Biochem, 1996 PubMed Europe PMC Scholia
  14. Zomer AW, de Weerd WF, Langeveld J, van den Bosch H; ''Ether lipid synthesis: purification and identification of alkyl dihydroxyacetone phosphate synthase from guinea-pig liver.''; Biochim Biophys Acta, 1993 PubMed Europe PMC Scholia
  15. Gallego-García A, Monera-Girona AJ, Pajares-Martínez E, Bastida-Martínez E, Pérez-Castaño R, Iniesta AA, Fontes M, Padmanabhan S, Elías-Arnanz M; ''A bacterial light response reveals an orphan desaturase for human plasmalogen synthesis.''; Science, 2019 PubMed Europe PMC Scholia
  16. Wainberg M, Kamber RA, Balsubramani A, Meyers RM, Sinnott-Armstrong N, Hornburg D, Jiang L, Chan J, Jian R, Gu M, Shcherbina A, Dubreuil MM, Spees K, Meuleman W, Snyder MP, Bassik MC, Kundaje A; ''A genome-wide atlas of co-essential modules assigns function to uncharacterized genes.''; Nat Genet, 2021 PubMed Europe PMC Scholia
  17. Keller MA, Zander U, Fuchs JE, Kreutz C, Watschinger K, Mueller T, Golderer G, Liedl KR, Ralser M, Kräutler B, Werner ER, Marquez JA; ''A gatekeeper helix determines the substrate specificity of Sjögren-Larsson Syndrome enzyme fatty aldehyde dehydrogenase.''; Nat Commun, 2014 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
142361view15:22, 30 January 2026DeSlUpdated SwissProt to TREMBL database Xref
142358view15:55, 28 January 2026Conroy lipidsupdated some bits, added a couple at the bottom, work in progress
142357view11:07, 28 January 2026Conroy lipids
142356view16:41, 27 January 2026Conroy lipids
142355view15:31, 27 January 2026Conroy lipidsadd lit refs and rhea
142333view14:32, 20 January 2026Conroy lipidsupdated RCDP4
141640view02:14, 21 November 2025EweitzRemove incorrect, deprecated metadata field
138712view03:01, 30 April 2025EweitzRefine organelle labels
138711view02:59, 30 April 2025EweitzEconomize layout
128241view23:30, 29 January 2024EweitzSoften disease color, standardize case
127389view21:42, 27 September 2023Conroy lipidsprotein to gene product
125918view02:47, 18 March 2023AlexanderPicomanual sync; removed dep link
125878view10:57, 16 March 2023DeSlVisualizing interactions without Rhea IDs
124539view16:49, 7 November 2022DeSlRemoved Rhea ID for mim-catalysis
124322view13:05, 13 October 2022DeSlUpdated name in description
124318view10:48, 13 October 2022DeSlAdded linkout for specific version of PWM expert endorcement
124317view10:46, 13 October 2022RobertMurphyUpdate description for expert curated PWM version
124315view10:44, 13 October 2022RobertMurphyReverted to version '13:20, 8 October 2022' by RobertMurphy
124314view10:23, 13 October 2022RobertMurphyModified description
124284view13:20, 8 October 2022EgonwMade a pathway clickable
124277view13:49, 6 October 2022Conroy lipidsmoved fatty alcohol production into the peroxisome, linked out to FA synthesis pathway
124276view13:36, 6 October 2022Conroy lipidsremoved fatty acid synthesis part, out of scope for this pathway.. Malonyl-CoA to FA is too great a simplification, and FA can be endogenous or dietry. Better to link to a FA synth pathway.
124263view10:26, 6 October 2022Conroy lipidsremoved incorrect Rhea of seminolipid-GalEAG. Reaction not currently in rhea, have contacted them
124172view09:24, 23 September 2022DeSlUpdate on PexRAP
124130view15:13, 21 September 2022DeSlUpdated mistyped PubMed ref.
124129view12:16, 21 September 2022DeSlAdded Rhea IDs for seminolipid conversions.
124126view12:01, 21 September 2022DeSlfinished adding Rhea IDs
124125view11:55, 21 September 2022DeSlAdded Rhea IDs for DG-O reactions
124124view11:51, 21 September 2022DeSlAdded Rhea ID for LPIN1,2,3 conversion
124123view11:46, 21 September 2022DeSlAdded some more RHEA IDS to interactions
124122view11:39, 21 September 2022DeSlUpdated PMID in description.
124121view11:31, 21 September 2022DeSlOntology Term : 'peroxisome biogenesis disorder 1A' added !
124120view11:31, 21 September 2022DeSlOntology Term : 'Zellweger syndrome pathway' added !
124119view11:30, 21 September 2022DeSlOntology Term : 'Zellweger syndrome' added !
124118view11:30, 21 September 2022DeSlAdded 4 main pex proteins related to peroxisome functioning and assembly, including two disorders.
124117view11:21, 21 September 2022DeSlOntology Term : 'rhizomelic chondrodysplasia punctata type 5' added !
124116view11:21, 21 September 2022DeSlAdded RCDP5
124115view09:29, 21 September 2022DeSlAdded RCDP4
124114view09:19, 21 September 2022DeSlOntology Term : 'rhizomelic chondrodysplasia punctata type 3' added !
124113view09:19, 21 September 2022DeSlOntology Term : 'rhizomelic chondrodysplasia punctata type 2' added !
124112view09:19, 21 September 2022DeSlOntology Term : 'rhizomelic chondrodysplasia punctata type 1' added !
124111view09:19, 21 September 2022DeSlOntology Term : 'rhizomelic chondrodysplasia punctata' added !
124110view09:18, 21 September 2022DeSlAdded RCDP2 and 3
124109view09:16, 21 September 2022DeSlAdded RCDP1 disorder
124108view09:14, 21 September 2022DeSlAdded info on AGPS import into peroxisome by PEX7, linekd to disease
124107view09:06, 21 September 2022DeSlAdded translocation of PexRap interaction
124106view08:55, 21 September 2022DeSlAdded conversion from Acyl-CoA to fatty alcohol
124105view08:38, 21 September 2022DeSlAdded transport of Acyl-Coa into Peroxisome
124104view08:27, 21 September 2022DeSlConnected two reactions catalyzed by same protein (CEPT1) to one DataNode iso 2
124103view08:25, 21 September 2022DeSlConnected unconnected lines, small layout changes

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ACSGeneProduct6.2.1.1 (Enzyme Nomenclature) AKA acyl-CoA synthetase; composed of two subunits.
AGPSGeneProductO00116 (Uniprot-TrEMBL)
ARSAGeneProductP15289 (Uniprot-TrEMBL)
Acyl-CoAMetaboliteLMFA07050000 (LIPID MAPS)
Acyl-GnPMetaboliteLMGP22010000 (LIPID MAPS)
Alkyl-GnPMetaboliteLMGP22020000 (LIPID MAPS)
CEPT1GeneProductQ9Y6K0 (Uniprot-TrEMBL)
Coenzyme AMetabolite15346 (ChEBI)
DG-OMetaboliteLMGL02020000 (LIPID MAPS)
DHAPMetabolite16108 (ChEBI) aka dihydroxyacetone phosphate
FAR1GeneProductQ8WVX9 (Uniprot-TrEMBL) AKA fatty acyl-CoA reductase.
FAR2GeneProductQ96K12 (Uniprot-TrEMBL) AKA fatty acyl-CoA reductase.
Fatty acid biosynthesisPathwayWP357 (WikiPathways)
Fatty acidMetaboliteCHEBI:57560 (ChEBI)
Fatty acidMetaboliteLMFA01010000 (LIPID MAPS)
Fatty alcoholMetaboliteLMFA05000000 (LIPID MAPS)
GAL3ST1GeneProductQ99999 (Uniprot-TrEMBL) EC 2.8.2.11
GNPATGeneProductO15228 (Uniprot-TrEMBL) AKA glyceronephosphate O-acyltransferase
GalEAGMetaboliteLMGL050200A0 (LIPID MAPS)
LPA-OMetaboliteLMGP10060000 (LIPID MAPS)
LPAMetaboliteLMGP10050000 (LIPID MAPS)
LPCAT1GeneProductQ8NF37 (Uniprot-TrEMBL)
LPIN1GeneProductQ14693 (Uniprot-TrEMBL)
LPIN2GeneProductQ92539 (Uniprot-TrEMBL)
LPIN3GeneProductQ9BQK8 (Uniprot-TrEMBL)
PA-OMetaboliteLMGP10020000 (LIPID MAPS)
PC-OMetaboliteLMGP01020000 (LIPID MAPS)
PE-OMetaboliteLMGP02020000 (LIPID MAPS)
PE-PMetaboliteLMGP02030000 (LIPID MAPS) AKA PE-Plasmalogen
PEDS1GeneProductA5PLL7 (Uniprot-TrEMBL)
PEX16GeneProductQ9Y5Y5 (Uniprot-TrEMBL)
PEX19GeneProductP40855 (Uniprot-TrEMBL)
PEX1GeneProductO43933 (Uniprot-TrEMBL)
PEX3GeneProductP56589 (Uniprot-TrEMBL)
PEX5LGeneProductQ8IYB4 (Uniprot-TrEMBL) 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]
PEX7GeneProductO00628 (Uniprot-TrEMBL) AKA peroxisomal import receptor for proteins, including AGPS [PMID:28523433]
PexRAP GeneProductQ6IAN0 (Uniprot-TrEMBL) AKA an acyl/alkyl DHAP reductase; "identified this gene as dhrs7b and renamed the protein PexRAP (for peroxisomal reductase activating PPARγ)" [PMID:28523433]
SeminolipidMetaboliteLMGL05020000 (LIPID MAPS)
UGT8GeneProductQ16880 (Uniprot-TrEMBL)
UNIDENTIFIEDProtein1.1.1.101 (Enzyme Nomenclature) Putative EC number as found in RHGEA entry https://www.rhea-db.org/rhea/36175

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
AGPSmim-catalysis36172 (Rhea)
Acyl-CoAAcyl-GnPmim-conversion17658 (Rhea)
Acyl-CoAFatty alcoholmim-conversion52717 (Rhea)
Acyl-GnPAlkyl-GnPmim-conversion36172 (Rhea)
Alkyl-GnPLPA-Omim-conversion36176 (Rhea)
DG-OPC-Omim-conversion36180 (Rhea)
DG-OPE-Omim-conversion36188 (Rhea)
GNPATmim-catalysis17658 (Rhea)
GalEAGSeminolipidmim-conversion41745 (Rhea)
LPA-OPA-Omim-conversion36236 (Rhea)
PA-ODG-Omim-conversion36240 (Rhea) Rhea ID matching based on EC-code overlap.
PE-OPE-Pmim-conversion22957 (Rhea)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP5275"