Omega-6-fatty acids in senescence (WP5424)

Homo sapiens

Oxylipins, notably prostaglandins, are synthetized by senescent cells and then accumulate, promoting the senescent-associated secretory phenotype (Wiley et al., 2021). The prostaglandins are classified into three main groups, depending on the starting point of their biosynthesis. The serie-1-prostaglandins are derived from its precursor dihomo-γ-linolenic acid (DGLA). The serie-2-prostaglandins and serie-3-prostaglandins are derived from arachidonic acid (AA) and eicosapentae-noic acid (EPA), respectively (Noverr et al., 2003)


JuliaUM , Andreapascaud , Egon Willighagen , Mra1221 , Denise Slenter , and Nikita Krstevska


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Homo sapiens



Pathway Ontology

fatty acid omega degradation pathway cellular senescence pathway lipid metabolic pathway


Label Type Compact URI Comment
15-keto-PGF2α Metabolite chebi:28442
Δ12-PGJ2 Metabolite chebi:28130 Synonym: 9-Deoxy-delta(9,12)-13,14-dihydro PGD2
12-oxo-10,11-dihydro-LTB4 Metabolite hmdb:HMDB0012498
12(S)-HETE Metabolite chebi:34146
IP3 Metabolite chebi:16595
15(S)-HETE Metabolite chebi:15558
15-keto-PGI2 Metabolite chebi:15556 =15-dehydro-Prostaglandin I2
10,11-dihydro-LTB4 Metabolite hmdb:HMDB0012504
15(R)-HpETE Metabolite chebi:82627
PGA2 Metabolite chebi:27820 PGA2=Prostaglandin A2
18-COOH-dinor-LTE4 Metabolite hmdb:HMDB0012607
10-HOTrE Metabolite pubchem.compound:54574843
5(S),6(S)-DiHETE Metabolite chebi:53026
HXA3 Metabolite chebi:36190
11α-hydroxy-9,15-dioxo-2,3,4,5,20-pentanor-19-carboxyprostanoic acid Metabolite chebi:73965
DH-PGJ2 Metabolite chebi:165318
18-COOH-dinor-LTB4 Metabolite chebi:63980
Adrenic acid (22:4,w6) Metabolite chebi:53487
12-oxo-LTB4 Metabolite pubchem.compound:5280876
N-acetyl- LTE4 Metabolite chebi:7210
EXC4 Metabolite chebi:63984
DH-15d-PGJ2 Metabolite pubchem.compound:16061095 =1a,1b-dihomo-15-deoxy-Δ12,14-prostaglandin J2
PGB1 Metabolite chebi:27624
TxB1 Metabolite pubchem.compound:71668258
Dihomo-y-linolenic acid (20:3,w6) Metabolite chebi:53486 = 8,11,14-Eicosatrienoic acid =DGLA
LXB4 Metabolite lipidmaps:LMFA03040002
15-epi-LXA4 Metabolite lipidmaps:LMFA03040010
EXD4 Metabolite chebi:63985
PGE1 Metabolite chebi:15544
15(S)-HpETE Metabolite chebi:15628
Tetracosapentaenoic acid (24:5,w-6) Metabolite hmdb:HMDB0006322
Bicyclo-PGE2 Metabolite chebi:89568
16-COOH-tetranor-LTE3 Metabolite chebi:74014
5(S),6(R)-DiHETE Metabolite pubchem.compound:5283160
15-keto-13,14-dihydro-PGE1 Metabolite chebi:134499
DH-PGF2α Metabolite chebi:183014
EXE4 Metabolite chebi:63986
TRXB3 Metabolite chebi:35032
13,14-dihydro-15-keto-PGD2 Metabolite chebi:72603 DK-PGD2
12(S)-HpETE Metabolite chebi:15626
15-epi-LXB4 Metabolite lipidmaps:LMFA03040007
PGH2 Metabolite chebi:15554 PGH2 is the abbreviation of PGG2
20-COOH-LTB4 Metabolite chebi:27562
13,14-dihydro-PGF2α Metabolite chebi:88346
5(S)-HETE Metabolite chebi:28209
DH-PGD2 Metabolite lipidmaps:LMFA03010156
DH-PGE2 Metabolite chebi:185711
LGE2 Metabolite chebi:34821 Levuglandin E2
LTF4 Metabolite chebi:27491
6-trans-LTB4 Metabolite chebi:63981
y-linolenic acid (18:3,w6) Metabolite chebi:28661 GLA(18:3 w6)
Ca2+ Metabolite chebi:29108
PGI2 Metabolite chebi:15552 Synonym for PGI2 is 'Prostacyclin'
LGD2 Metabolite chebi:34820 Levuglandin D2
9α,11α-PGF2α Metabolite chebi:15553
9α,11β-PGF2α Metabolite chebi:15553
13,14-dihydro-15-keto-PGE2 Metabolite chebi:15550 PGEM= Metabolites downstream of PGE2
EXA4 Metabolite chebi:63983
Eicosadienoic acid (20:2,w6) Metabolite chebi:73731
PGG1 Metabolite chebi:133739
PGC1 Metabolite chebi:15546
Tetranor-PGDM Metabolite lipidmaps:LMFA03010221
PGF1α Metabolite chebi:28852
TRXA3 Metabolite chebi:36203
PGA1 Metabolite cas:14152-28-4
Linoleic acid (18:2,w6) Metabolite chebi:17351 LA (18:2 w6)
cAMP Metabolite chebi:17489
15-keto-PGD2 Metabolite chebi:15557
HXB3 Metabolite chebi:34784
Arachidonic Acid (20:4,w6) Metabolite chebi:15843
2,3 dinor-6-keto-PGF1α Metabolite chebi:73944
6-keto-PGF1α Metabolite chebi:28158
DH-15d-Δ12,14-PGD2 Metabolite chebi:165317
5(S),6(S)-epoxy-15(S)-HETE Metabolite chebi:64095
13,14-dihydro-15-keto-PGA2 Metabolite chebi:89315 8: Prostanoid Metabolites as Biomarkers in Human Disease Helena Idborg; Sven-Christian Pawelzik. 2022. PubMed 36005592.
Ca2+ Metabolite chebi:29108 calcium
9-deoxy-Δ12-PGD2* Metabolite chebi:175297
15-keto-13,14-dihydro-PGF2α Metabolite chebi:63976
LXA4 Metabolite lipidmaps:LMFA03040001
11-dehydro-TxB2 Metabolite chebi:28667
6-keto-PGE1 Metabolite chebi:28269
PGE2 Metabolite chebi:15551
Osbond acid (22:5,w6) Metabolite chebi:53488 =docosapentaenoic acid (DPAω6, 22:5)
Tetracosatetraenoic acid (24:4, w-6) Metabolite hmdb:HMDB0006246
20-COOH-LTE4 Metabolite pubchem.compound:53481508
IP3 Metabolite chebi:16595
19-OH-PGE1 Metabolite cas:55123-67-6
PGD2 Metabolite chebi:15555
PGH1 Metabolite chebi:91133
PGJ2 Metabolite chebi:27485
15-keto-PGE1 Metabolite cas:22973-19-9
PGD1 Metabolite chebi:27696
TxA Metabolite chebi:15627
PGG2 Metabolite chebi:27647 Prostaglandin G2 is abbreviated as PGG2
Δ6-trans-12-epi-LTB4 Metabolite chebi:63982
15-deoxy-Δ12,14-PGJ2 Metabolite chebi:34159 =15d-PGJ2
19-OH-PGE2 Metabolite chebi:165313
15-keto-PGE2 Metabolite chebi:15547
PGC2 Metabolite chebi:27555 PGC2=Prostaglandin C2
PGB2 Metabolite chebi:28099 PGB2=Prostaglandin B2
TxB Metabolite chebi:28728
cAMP Metabolite chebi:17489 PGI2 binding to the associated IP receptor (coupled to Gs) leads to an activation of the AC and thus to an increase of intracellular cAMP. Its elevation downregulates store-mediated calcium entry, calcium mobilization and secretion, as well as platelet adhesion to subendothelial collagen via integrin α2β1. The cAMP increase further results in an activation of protein kinase-A (PKA) and in principle, in an inhibition of platelet activation. Analogous to cAMP, PKA activity has been associated with a reduced Ca2+ release from intra-platelet stores
Membrane phospholipids Metabolite chebi:16247
19-OH-6-keto-PGF1α Metabolite chebi:172589
6,15-Diketo-13,14-dihydro-PGF1α Metabolite chebi:72595
2,3-dinor-11β-PGF2α Metabolite chebi:165323
2,3-Dinor-TxB2 Metabolite chebi:89991
15-deoxy-Δ12,14-PGD2 Metabolite chebi:63999 =15d-PGJ2
LTB4 Metabolite chebi:15647
5(S)-HpETE Metabolite hmdb:HMDB11135
LTD4 Metabolite chebi:28666
LTA4 Metabolite chebi:15651
LTE4 Metabolite chebi:15650
LTC4 Metabolite chebi:16978
DH-PGI2 Metabolite chebi:165328
ROS Metabolite chebi:26523
20-OH-LTB4 Metabolite chebi:15646
8-iso-15-keto-PGF2α Metabolite chebi:175523
2,3-dinor-8-IsoPGF2α Metabolite pubchem.compound:9548881
8-iso-13,14-dihydro-15-keto-PGF2α Metabolite lipidmaps:LMFA03110004
15-F2-IsoP Metabolite chebi:187201 = 8-iso-PGF2a
15-D2-IsoP Metabolite lipidmaps:LMFA03110099 Iso-Prostaglandin H2
15-J2-IsoP Metabolite lipidmaps:LMFA03110101 Iso-Prostaglandin H2
15-A2-IsoP Metabolite lipidmaps:LMFA03110138 Iso-Prostaglandin H2
12-F2-IsoP Metabolite lipidmaps:LMFA03110042 Iso-Prostaglandin H2
12-D2-IsoP Metabolite lipidmaps:LMFA03110085 Iso-Prostaglandin H2
12-J2-IsoP Metabolite lipidmaps:LMFA03110087 Iso-Prostaglandin H2
12-15d-J2-IsoP Metabolite lipidmaps:LMFA03110090 Iso-Prostaglandin H2
12-E2-IsoP Metabolite lipidmaps:LMFA03110190 Iso-Prostaglandin H2
12-A2-IsoP Metabolite lipidmaps:LMFA03110248 Iso-Prostaglandin H2
8-F2-IsoP Metabolite lipidmaps:8-F2t-IsoP
8-D2-IsoP Metabolite lipidmaps:LMFA03110057 Iso-Prostaglandin H2
8-J2-IsoP Metabolite lipidmaps:LMFA03110059 Iso-Prostaglandin H2
8-15d-J2-IsoP Metabolite lipidbank:LMFA03110062 Iso-Prostaglandin H2
8-E2-IsoP Metabolite lipidmaps:LMFA03110003 Iso-Prostaglandin H2
5-F2-IsoP Metabolite lipidmaps:LMFA03110039 Iso-Prostaglandin H2
5-D2-IsoP Metabolite lipidmaps:LMFA03110070 Iso-Prostaglandin H2
5-J2-IsoP Metabolite lipidmaps:LMFA03110072 Iso-Prostaglandin H2
5-15d-J2-IsoP Metabolite lipidmaps:LMFA03110075 Iso-Prostaglandin H2
5-E2-IsoP Metabolite lipidmaps:LMFA03110174 Iso-Prostaglandin H2
5-A2-IsoP Metabolite lipidmaps:LMFA03110257 Iso-Prostaglandin H2
7-DH-F2-IsoP Metabolite lipidmaps:LMFA03110299
14-DH-F2-IsoP Metabolite lipidmaps:LMFA03110331
10-DH-F2-IsoP Metabolite lipidmaps:LMFA03110315
17-DH-F2-IsoP Metabolite lipidmaps:LMFA03110347
11-deoxy-13,14-dihydro-15-keto-11β,16-cyclo-PGE1 Metabolite cas:1283861-32-4
Δ13-reductase GeneProduct ensembl:ENSG00000140043 =15-oxoprostaglandin-Δ13-reductase
p53 GeneProduct ensembl:ENSG00000141510
CYP4F8 GeneProduct ensembl:ENSG00000186526
PTGES GeneProduct ensembl:ENSG00000148344 =microsomal prostaglandin E synthase 1 (mPGES-1)
PGFS GeneProduct ensembl:ENSG00000157870 =Prostaglandin F synthase
15-ketoprostaglandin reductase GeneProduct ensembl:ENSG00000140043
NAT1 GeneProduct ensembl:ENSG00000171428
ALOX15 GeneProduct ensembl:ENSG00000161905
SLCO2A1 GeneProduct ensembl:ENSG00000174640
PGES GeneProduct ensembl:ENSG00000148344 =prostaglandin E synthase
γ-GT GeneProduct ensembl:ENSG00000100031 Identical to GGT1
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TBXAS1 GeneProduct ensembl:ENSG00000059377 =CYP5A1
Carboxypeptidase A GeneProduct eccode:
GPX1 GeneProduct ensembl:ENSG00000233276
ALOXE3 GeneProduct ensembl:ENSG00000179148
2,4-dienoyl-CoA reductase GeneProduct ensembl:ENSG00000104325
EPHX2 GeneProduct ensembl:ENSG00000120915
PGDS GeneProduct ensembl:ENSG00000107317 =Prostaglandin D synthase
15-ketoprostaglandin reductase GeneProduct ensembl:ENSG00000140043
ABCC4 GeneProduct ensembl:ENSG00000125257
PG-9KR GeneProduct ensembl:ENSG00000159228 PG-9KR= Prostaglandin-9-ketoreductase
DPEP GeneProduct eccode:
AKR1C3 GeneProduct ensembl:ENSG00000196139 =aldo-keto reductase family 1 member C3
CYP4F8 GeneProduct ensembl:ENSG00000186526
H-PGDS GeneProduct ensembl:ENSG00000163106
PGDS GeneProduct ensembl:ENSG00000107317
PGE synthase GeneProduct ensembl:ENSG00000148344
TXAS GeneProduct ensembl:ENSG00000059377 =Thromboxane synthase
CYP4F8 GeneProduct ensembl:ENSG00000186526 =cytochrome P450 family 4 subfamily F member 8
LTC4S GeneProduct ensembl:ENSG00000213316
NAT2 GeneProduct ensembl:ENSG00000156006
ALOX15B GeneProduct ensembl:ENSG00000179593
p21 GeneProduct ensembl:ENSG00000124762
GPX1 GeneProduct ensembl:ENSG00000233276
PGES GeneProduct ensembl:ENSG00000148344 =Prostaglandin E synthase
ALOX12 GeneProduct ensembl:ENSG00000108839
ALOX12 GeneProduct ensembl:ENSG00000108839
HPGD GeneProduct ensembl:ENSG00000164120 15-PGDH=15-hydroxy-prostaglandin dehydrogenase
L-PGDS GeneProduct ensembl:ENSG00000107317
CYP8A1 GeneProduct ensembl:ENSG00000124212 =prostaglandin I2 synthase =PTGIS
AKR1B1 GeneProduct ensembl:ENSG00000085662
AKR1C3 GeneProduct ensembl:ENSG00000196139 =NADPH-dependent PGD2 11-ketoreductase =aldo-keto reductase family 1 member C3 =EC
GSTP1 GeneProduct ensembl:ENSG00000084207
GGT1 GeneProduct ensembl:ENSG00000100031
PTGES2 GeneProduct ensembl:ENSG00000148334 =microsomal prostaglandin E synthase 2 (PTGES2)
PTGES3 GeneProduct ensembl:ENSG00000110958 =prostaglandin E synthase 3 (cPGES)
AKR1B1 GeneProduct ensembl:ENSG00000085662 =aldo-keto reductase family 1 member B
p38 MAPK GeneProduct ensembl:ENSG00000185386
11-hydroxythromboxane B2 dehydrogenase GeneProduct ensembl:ENSG00000165092 11-hydroxythromboxane B2 dehydrogenase is the same as cytosolic aldehyde dehydrogenase
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PTGS1 GeneProduct ensembl:ENSG00000095303 Prostaglandin-endoperoxide synthase 1 =cyclooxygenase (COX)
PTGS2 GeneProduct ensembl:ENSG00000073756 prostaglandin-endoperoxide synthase 2 =cyclooxygenase (COX)
ELOVL2 GeneProduct ensembl:ENSG00000197977 fatty acid elongase 2
ELOVL5 GeneProduct ensembl:ENSG00000012660 fatty acid elongase 5
FADS2 GeneProduct ensembl:ENSG00000134824 gene=FADS2 Δ6-Desaturase
FADS1 GeneProduct ensembl:ENSG00000149485 Δ5-Desaturase
ELOVL5 GeneProduct ensembl:ENSG00000012660 fatty acid elongase 5
Δ13-reductase GeneProduct ensembl:ENSG00000140043 =15-oxo-prostaglandin Δ13-reductase
Δ13-reductase GeneProduct eccode: =15-oxoprostaglandin-Δ13-reductase
DPEP1 GeneProduct ensembl:ENSG00000015413 =Human microsomal dipeptidase (MDP, formerly referred to as dehydropeptidase-I or renal dipeptidase) [EC]
GGT1 GeneProduct ensembl:ENSG00000100031
DPEP2 GeneProduct ensembl:ENSG00000167261
LTC4S GeneProduct ensembl:ENSG00000213316
GGT5 GeneProduct ensembl:ENSG00000099998 =gamma-glutamyltransferase 5
LTA4H GeneProduct ensembl:ENSG00000111144
ALOX5 GeneProduct ensembl:ENSG00000012779 =arachidonate 5-lipoxygenase
FLAP GeneProduct ensembl:ENSG00000132965 gene = ALOX5AP FLAP= 5-lipoxygenase activating protein
HPGD GeneProduct ensembl:ENSG00000164120 15-PGDH=15-hydroxy-prostaglandin dehydrogenase
HPGD GeneProduct ensembl:ENSG00000164120 15-PGDH=15-hydroxy-prostaglandin dehydrogenase
HPGD GeneProduct ensembl:ENSG00000164120 15-PGDH=15-hydroxy-prostaglandin dehydrogenase
SIRT1 GeneProduct ensembl:ENSG00000096717
p53 GeneProduct ensembl:ENSG00000141510 Gene: TP53
p53 GeneProduct ensembl:ENSG00000141510
p21 GeneProduct ensembl:ENSG00000124762 Gene: CDKN1A
Rb GeneProduct ensembl:ENSG00000139687
Rb GeneProduct ensembl:ENSG00000139687
p53 GeneProduct ensembl:ENSG00000141510
HPGD GeneProduct ensembl:ENSG00000164120 15-PGDH=15-hydroxy-prostaglandin dehydrogenase
ELOVL2 GeneProduct ensembl:ENSG00000197977 fatty acid elongase 2
FADS2 GeneProduct ensembl:ENSG00000134824 gene=FADS2 Δ6-Desaturase
ALOX15 GeneProduct ensembl:ENSG00000161905
PTGS2 GeneProduct ensembl:ENSG00000073756
ALOX5 GeneProduct ensembl:ENSG00000012779 =arachidonate 5-lipoxygenase
ALOX15B GeneProduct ensembl:ENSG00000179593
ALOX15B GeneProduct ensembl:ENSG00000179593
ALOX15 GeneProduct ensembl:ENSG00000161905
ALOX15 GeneProduct ensembl:ENSG00000161905
GSH Protein kegg.genes:C00051 Cofactor
Cytosolic phospholipase A2 Protein uniprot:P47712
Cytosolic phospholipase A2 Protein uniprot:P47712
CysLT1R Protein ensembl:ENSG00000173198 =cysteinyl leukotriene type 1 receptor
PAI-1 Protein ensembl:ENSG00000106366 Gene: SERPINE1
Cytosolic phospholipase A2 Protein uniprot:P47712


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