Linoleic acid metabolism affected by SARS-CoV-2 (Homo sapiens)

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"Upon HCoV-229E infection, the glycerophospholipids, as main components of the cell membrane, were metabolized to lysophospholipids (LysPx) and Fatty Acids (FAs) after cPLA2 enzyme activation." [PMID:30654597]palmitic acidLysPE 16:0Arachidonic acidbishomo-gamma-linolenic acidLysoPC16:0Linoleoyl-CoAdesaturaseoleic acidlinoleic acidSARS-CoV-2 and COVID-19 PathwayMolecular mechanismGlycerophospholipidsCytosolic Phospholipase A2(cPLA2)gamma-linolenic acid2HCoV-229Etrimersurfaceglycoprotein Ssurfaceglycoprotein Smembraneglycoprotein M1, 3SARS-CoV-2RNA1nucleocapsidprotein N1envelopeprotein E1


Description

Collaborative project for curation biological processes involved in the COVID-19 disease after SARS-Cov-2 infection. It focuses on experimental evidence and plays with improved annotation of complexes and with the Evidence and Conclusion Ontology. The complexes link to EBI's Complex Portal, resulting from a collaboration with that database at the recent online ELIXIR biohackathon.

Editing this pathway is (at this moment) coordinated via the wikipathways.slack.com #sarscov2 channel.

The large viral Spike protein (S or surface glycoprotein) forms trimers. It interacts with the host's ACE2 receptor to establish binding (Hoffmann et al 2020). There are suggestions for more than one cell entry mechanism, with the evidence for ACE2/TMPRSS2 entry being most clear now. Lack of expression of TMPRSS2 may explain age differences in COVID19 severity. In this mechanism, to enter the virus needs to be primed by the host protease TMPRSS2 that splits the Spike protein into 2 peptides S1 and S2. S1 contains the ACE2 receptor binding site, S2 binds to the host cell membrane which leads to membrane fusion, the start of the uptake process. The ACE2 receptor interaction was also suggested as the start of specific lung-damaging effects.

Other human genes that may be involved in alternative cell uptake mechanisms include CTSL and SLC6A19.

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Bibliography

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  1. Paces J, Strizova Z, Smrz D, Cerny J; ''COVID-19 and the immune system.''; Physiol Res, 2020 PubMed Europe PMC Scholia
  2. Dennis EA, Deems RA, Harkewicz R, Quehenberger O, Brown HA, Milne SB, Myers DS, Glass CK, Hardiman G, Reichart D, Merrill AH Jr, Sullards MC, Wang E, Murphy RC, Raetz CR, Garrett TA, Guan Z, Ryan AC, Russell DW, McDonald JG, Thompson BM, Shaw WA, Sud M, Zhao Y, Gupta S, Maurya MR, Fahy E, Subramaniam S; ''A mouse macrophage lipidome.''; J Biol Chem, 2010 PubMed Europe PMC Scholia
  3. Goc A, Niedzwiecki A, Rath M; ''Polyunsaturated ω-3 fatty acids inhibit ACE2-controlled SARS-CoV-2 binding and cellular entry.''; Sci Rep, 2021 PubMed Europe PMC Scholia
  4. Kandeel M, Ibrahim AA, Fayez M, Al-Nazawi M; ''From SARS and MERS CoVs to SARS-CoV-2: moving toward more biased codon usage in viral structural and non-structural genes.''; J Med Virol, 2020 PubMed Europe PMC Scholia
  5. Hathaway D, Pandav K, Patel M, Riva-Moscoso A, Singh BM, Patel A, Min ZC, Singh-Makkar S, Sana MK, Sanchez-Dopazo R, Desir R, Fahem MMM, Manella S, Rodriguez I, Alvarez A, Abreu R; ''Omega 3 Fatty Acids and COVID-19: A Comprehensive Review.''; Infect Chemother, 2020 PubMed Europe PMC Scholia
  6. Yan B, Chu H, Yang D, Sze KH, Lai PM, Yuan S, Shuai H, Wang Y, Kao RY, Chan JF, Yuen KY; ''Characterization of the Lipidomic Profile of Human Coronavirus-Infected Cells: Implications for Lipid Metabolism Remodeling upon Coronavirus Replication.''; Viruses, 2019 PubMed Europe PMC Scholia
  7. Casari I, Manfredi M, Metharom P, Falasca M; ''Dissecting lipid metabolism alterations in SARS-CoV-2.''; Prog Lipid Res, 2021 PubMed Europe PMC Scholia
  8. Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D; ''Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein.''; Cell, 2020 PubMed Europe PMC Scholia
  9. Grimes JM, Grimes KV; ''p38 MAPK inhibition: A promising therapeutic approach for COVID-19.''; J Mol Cell Cardiol, 2020 PubMed Europe PMC Scholia
  10. Miao H, Chen L, Hao L, Zhang X, Chen Y, Ruan Z, Liang H; ''Stearic acid induces proinflammatory cytokine production partly through activation of lactate-HIF1α pathway in chondrocytes.''; Sci Rep, 2015 PubMed Europe PMC Scholia
  11. Nakazato Y, Sedor JR; ''IL-1 alpha increases arachidonyl-CoA: lysophospholipid acyltransferase activity and stimulates [3H]arachidonate incorporation into phospholipids in rat mesangial cells.''; Life Sci, 1992 PubMed Europe PMC Scholia
  12. Arnardottir H, Pawelzik SC, Öhlund Wistbacka U, Artiach G, Hofmann R, Reinholdsson I, Braunschweig F, Tornvall P, Religa D, Bäck M; ''Stimulating the Resolution of Inflammation Through Omega-3 Polyunsaturated Fatty Acids in COVID-19: Rationale for theCOVID-Omega-FTrial.''; Front Physiol, 2020 PubMed Europe PMC Scholia
  13. Sigrist CJ, Bridge A, Le Mercier P; ''A potential role for integrins in host cell entry by SARS-CoV-2.''; Antiviral Res, 2020 PubMed Europe PMC Scholia
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  16. Müller C, Hardt M, Schwudke D, Neuman BW, Pleschka S, Ziebuhr J; ''Inhibition of Cytosolic Phospholipase A2α Impairs an Early Step of Coronavirus Replication in Cell Culture.''; J Virol, 2018 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
128505view23:27, 10 February 2024EweitzOntology Term : 'linoleic acid metabolic pathway' added !
128504view23:25, 10 February 2024EweitzTailor node dimensions, refine case
124602view19:22, 15 November 2022EgonwReplaced an old LIPID MAPS identifier
124589view06:21, 13 November 2022EgonwConverted to labels involved in interactions into data node
123346view10:01, 17 July 2022EgonwAdded two identifiers
122756view16:04, 10 May 2022EgonwMade a pathway clickable
121908view10:24, 8 March 2022CedricPluisfix positions
121907view10:23, 8 March 2022CedricPluisfix interactions
121906view10:22, 8 March 2022CedricPluisfix positions
121904view10:18, 8 March 2022CedricPluisfix interactions
121901view10:13, 8 March 2022CedricPluisarrows changed
121831view09:19, 7 March 2022BramMennenInteraction lines were changed to make the pathway easier to understand
121823view06:50, 7 March 2022EgonwAssuming a typo in LipidMaps identifier: PG -> GP
121639view08:11, 23 February 2022CedricPluischange reference
121628view10:48, 22 February 2022CedricPluisModified title
121627view10:47, 22 February 2022CedricPluisarrow change
121619view09:53, 22 February 2022CedricPluisstearic acid and cytokine storm
121618view09:52, 22 February 2022CedricPluislay-out
121617view09:51, 22 February 2022CedricPluislay-out
121616view09:42, 22 February 2022CedricPluisposition changes
121615view09:38, 22 February 2022CedricPluisposition changes
121611view09:17, 22 February 2022Liekevandenbogaart-
121610view09:16, 22 February 2022CedricPluisAddition of data node pathway covid immune response
121348view08:56, 16 February 2022CedricPluisfix interactions
121347view08:54, 16 February 2022CedricPluisfix interactions
121342view14:52, 15 February 2022CedricPluisconnect lines
121340view13:02, 15 February 2022CedricPluisCPLA2 activation by MAP kinase
121339view13:01, 15 February 2022CedricPluisActivation of MAP kinase
121338view12:36, 15 February 2022CedricPluisMAP kinase
121336view12:16, 15 February 2022CedricPluisace-2
121335view12:13, 15 February 2022CedricPluisace-2 binding and inhibition by produced fatty acids
121333view12:08, 15 February 2022CedricPluisrole of formed fatty acids added
121332view12:03, 15 February 2022CedricPluisRole of omega-3 and omega-6 added
121331view11:53, 15 February 2022CedricPluisChanges in virus structure and addition of the formation of cytokine storm by AA
121243view08:36, 14 February 2022CedricPluis
121242view08:35, 14 February 2022CedricPluis
121230view11:49, 13 February 2022EgonwModified description
119386view16:18, 25 June 2021EgonwNot a mim-conversion
118839view09:19, 2 June 2021EweitzOntology Term : 'DOID:934' removed !
118838view09:19, 2 June 2021EweitzOntology Term : 'Coronavirus infectious disease' added !
118052view10:32, 24 May 2021EweitzModified title
115866view16:12, 18 March 2021DeSlAdded shape around PW node
115864view16:08, 18 March 2021DeSlAdded missing metabolites for dashed lines
111153view08:33, 21 July 2020EgonwMade the pathway clickable
110787view09:11, 5 June 2020DeSlModified title
110786view08:57, 5 June 2020DeSlModified description
110785view08:56, 5 June 2020DeSlAdded lit ref for stimulation of cPLA2
110784view08:55, 5 June 2020DeSlUpdated title again (was accidentally overwritten).
110783view08:53, 5 June 2020DeSlAdded details on how HCoV-229E is related to lipid metabolism alterations.
110457view08:40, 13 May 2020Mkutmonfixed unconnected lines, layout

External references

DataNodes

View all...
NameTypeDatabase referenceComment
Arachidonic acidMetaboliteLMFA01030001 (LIPID MAPS)
Cytosolic Phospholipase A2 (cPLA2)GeneProduct3.1.1.4 (BRENDA)
GlycerophospholipidsMetaboliteCHEBI:37739 (ChEBI)
Linoleoyl-CoA

desaturase

GeneProduct1.14.19.3 (BRENDA)
LysPE 16:0Metabolite
LysoPC16:0MetaboliteLMGP01050113 (LIPID MAPS)
SARS-CoV-2 RNARnaQ82069695 (Wikidata)
SARS-CoV-2 and

COVID-19 Pathway

Molecular mechanism		PathwayWP4846 (WikiPathways)
bishomo-gamma-linolenic acidMetaboliteLMFA01030158 (LIPID MAPS)
envelope protein EProteinP0DTC4 (Uniprot-TrEMBL)
gamma-linolenic acidMetaboliteLMFA01030141 (LIPID MAPS)
linoleic acidMetaboliteLMFA01030120 (LIPID MAPS)
membrane glycoprotein MProteinP0DTC5 (Uniprot-TrEMBL)
nucleocapsid protein NProteinP0DTC9 (Uniprot-TrEMBL)
oleic acid MetaboliteLMFA01030002 (LIPID MAPS)
palmitic acidMetaboliteLMFA01010001 (LIPID MAPS)
surface glycoprotein SProteinP0DTC2 (Uniprot-TrEMBL)
trimerComplexCPX-5682 (Complex Portal)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP4853"
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