Ether lipid biosynthesis (Homo sapiens)

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Endoplasmic reticulum10 Peroxisome101014105310268RCDP1UNIDENTIFIEDLPCAT1FASPEX5LSeminolipidPE-OGAL3ST1Malonyl CoADHAPGalEAGPE-PPA-OPEX7GNPATACSFatty acidUGT8LPIN2LPIN3Fatty alcoholAlkyl-DHAPAcyl-CoALPA-OCoenzyme ALPIN1ARSAPexRAP Acyl-DHAPLPAPC-OAGPSDG-OPEDS19Acyl-CoACoenzyme ACEPT17Alkyl-DHAP7Acyl-CoAFatty Acid10Fatty Alcohol10FAR1FAR21010Acyl-DHAP1010AGPSRCDP2RCDP3RCDP4PEX7RCDP510


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 facilitating membrane fusion processes). Lipid raft microdomains (cholesterol-rich membrane regions involved in cellular signaling) rely on ether lipids for their organization and stability. [PMID:2852343].

The pathway knowledge depicted in this model stems from Bob Murphy.

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Ontology Terms

 

Bibliography

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  1. 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
  2. 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
  3. 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
  4. John M. Dean, Irfan J. Lodhi; ''Structural and functional roles of ether lipids''; Protein Cell., 2018 PubMed Europe PMC Scholia
  5. Henneberry AL, McMaster CR; ''Cloning and expression of a human choline/ethanolaminephosphotransferase: synthesis of phosphatidylcholine and phosphatidylethanolamine.''; Biochem J, 1999 PubMed Europe PMC Scholia
  6. 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
  7. Han GS, Carman GM; ''Characterization of the human LPIN1-encoded phosphatidate phosphatase isoforms.''; J Biol Chem, 2010 PubMed Europe PMC Scholia
  8. 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
  9. 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
  10. 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

History

View all...
CompareRevisionActionTimeUserComment
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
124102view08:22, 21 September 2022DeSlUpdated all GeneProducts to Proteins
124101view08:20, 21 September 2022DeSlUpdated description, added new ref. to full PWM.
123734view07:33, 12 August 2022Conroy lipidsanchor again
123733view07:30, 12 August 2022Conroy lipidsfix anchor again
123732view07:23, 12 August 2022Conroy lipidsfixed anchor
123731view15:16, 11 August 2022Conroy lipidsadd achors
123705view08:41, 11 August 2022DeSlChanged visualization of cellular compartments
123704view08:36, 11 August 2022DeSlOntology Term : 'lipid metabolic pathway' added !
123703view08:35, 11 August 2022DeSlOntology Term : 'ether lipid metabolic pathway' added !

External references

DataNodes

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NameTypeDatabase referenceComment
ACSProtein6.2.1.1 (Enzyme Nomenclature) AKA acyl-CoA synthetase; composed of two subunits.
AGPSProteinO00116 (Uniprot-TrEMBL)
ARSAProteinP15289 (Uniprot-TrEMBL)
Acyl-CoAMetaboliteLMFA07050000 (LIPID MAPS)
Acyl-DHAPMetaboliteLMGP22010000 (LIPID MAPS)
Alkyl-DHAPMetaboliteLMGP22020000 (LIPID MAPS)
CEPT1ProteinQ9Y6K0 (Uniprot-TrEMBL)
Coenzyme AMetabolite15346 (ChEBI)
DG-OMetaboliteLMGL02020000 (LIPID MAPS)
DHAPMetabolite16108 (ChEBI) aka dihydroxyacetone phosphate
FAR1ProteinQ8WVX9 (Uniprot-TrEMBL) AKA fatty acyl-CoA reductase.
FAR2ProteinQ96K12 (Uniprot-TrEMBL) AKA fatty acyl-CoA reductase.
FASProteinP49327 (Uniprot-TrEMBL)
Fatty AcidMetaboliteCHEBI:57560 (ChEBI)
Fatty AlcoholMetaboliteLMFA05000000 (LIPID MAPS)
Fatty acidMetaboliteLMFA01010000 (LIPID MAPS)
Fatty alcoholMetaboliteLMFA05000000 (LIPID MAPS)
GAL3ST1ProteinQ99999 (Uniprot-TrEMBL) EC 2.8.2.11
GNPATProteinO15228 (Uniprot-TrEMBL) AKA glyceronephosphate O-acyltransferase
GalEAGMetaboliteLMGL050200A0 (LIPID MAPS)
LPA-OMetaboliteLMGP10060000 (LIPID MAPS)
LPAMetaboliteLMGP10050000 (LIPID MAPS)
LPCAT1ProteinQ8NF37 (Uniprot-TrEMBL)
LPIN1ProteinQ14693 (Uniprot-TrEMBL)
LPIN2ProteinQ92539 (Uniprot-TrEMBL)
LPIN3ProteinQ9BQK8 (Uniprot-TrEMBL)
Malonyl CoAMetaboliteCHEBI:57384 (ChEBI)
PA-OMetaboliteLMGP10020000 (LIPID MAPS)
PC-OMetaboliteLMGP01020000 (LIPID MAPS)
PE-OMetaboliteLMGP02020000 (LIPID MAPS)
PE-PMetaboliteLMGP02030000 (LIPID MAPS)
PEDS1ProteinA5PLL7 (Uniprot-TrEMBL)
PEX5LProteinQ8IYB4 (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:2852343]. AGPS contains a PTS2 domain (type-2 peroxisomal targeting signal). [PMID:31751594]
PEX7ProteinO00628 (Uniprot-TrEMBL) AKA peroxisomal import receptor for proteins, including AGPS [PMID:2852343]
PexRAP ProteinQ6IAN0 (Uniprot-TrEMBL) AKA an acyl/alkyl DHAP reductase; "identified this gene as dhrs7b and renamed the protein PexRAP (for peroxisomal reductase activating PPARγ)" [PMID:2852343]
SeminolipidMetaboliteLMGL05020000 (LIPID MAPS)
UGT8ProteinQ16880 (Uniprot-TrEMBL)

Annotated Interactions

SourceTargetTypeDatabase referenceComment
Acyl-CoAAcyl-DHAPmim-conversion17658 (Rhea)
Acyl-CoAFatty Alcoholmim-conversion52717 (Rhea)
Malonyl CoAFatty Acidmim-conversion14994 (Rhea)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP5275"
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