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.
Authors
Conroy lipids , Denise Slenter , Egon Willighagen , Robert C. Murphy , Alex Pico , and Eric WeitzActivity
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Organisms
Homo sapiensCommunities
Inherited Metabolic Disorders (IMD) Pathways Lipids and LIPID MAPSAnnotations
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 2Pathway 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:6.2.1.1 | 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 2.8.2.11 |
| 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:1.1.1.101 | Putative EC number as found in RHGEA entry https://www.rhea-db.org/rhea/36175 |
References
- 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
- Ether lipid synthesis: purification and identification of alkyl dihydroxyacetone phosphate synthase from guinea-pig liver. Zomer AW, de Weerd WF, Langeveld J, van den Bosch H. Biochim Biophys Acta. 1993 Oct 13;1170(2):189–96. PubMed Europe PMC Scholia
- Purification and characterization of 3’-phosphoadenosine-5’-phosphosulfate:GalCer sulfotransferase from human renal cancer cells. Honke K, Yamane M, Ishii A, Kobayashi T, Makita A. J Biochem. 1996 Mar;119(3):421–7. PubMed Europe PMC Scholia
- Cloning and expression of a human choline/ethanolaminephosphotransferase: synthesis of phosphatidylcholine and phosphatidylethanolamine. Henneberry AL, McMaster CR. Biochem J. 1999 Apr 15;339 ( Pt 2)(Pt 2):291–8. PubMed Europe PMC Scholia
- Requirement of seminolipid in spermatogenesis revealed by UDP-galactose: Ceramide galactosyltransferase-deficient mice. Fujimoto H, Tadano-Aritomi K, Tokumasu A, Ito K, Hikita T, Suzuki K, et al. J Biol Chem. 2000 Jul 28;275(30):22623–6. PubMed Europe PMC Scholia
- Role of dihydroxyacetonephosphate acyltransferase in the biosynthesis of plasmalogens and nonether glycerolipids. Liu D, Nagan N, Just WW, Rodemer C, Thai TP, Zoeller RA. J Lipid Res. 2005 Apr;46(4):727–35. PubMed Europe PMC Scholia
- 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
- 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
- Structural and functional roles of ether lipids. Dean JM, Lodhi IJ. Protein Cell. 2018 Feb;9(2):196–206. PubMed Europe PMC Scholia
- 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