Details of Metabolite

General Information of MET (ID: META00001)
Name 12-HETE
Synonyms   Click to Show/Hide Synonyms of This Metabolite
(12S)-12-Hydroxy-5,8,14-cis-10-trans-eicosatetraenoate; (12S)-12-Hydroxy-5,8,14-cis-10-trans-eicosatetraenoic acid; (5Z,8Z,10E,12S,14Z)-12-Hydroxyeicosa-5,8,10,14-tetraenoate; (5Z,8Z,10E,12S,14Z)-12-Hydroxyeicosa-5,8,10,14-tetraenoic acid; (5Z,8Z,10E,14Z)-(12S)-12-Hydroxyeicosa-5,8,10,14-tetraenoate; (5Z,8Z,10E,14Z)-(12S)-12-Hydroxyeicosa-5,8,10,14-tetraenoic acid; (5Z,8Z,10E,14Z)-(12S)-12-Hydroxyicosa-5,8,10,14-tetraenoate; (5Z,8Z,10E,14Z)-(12S)-12-Hydroxyicosa-5,8,10,14-tetraenoic acid; (5Z,8Z,10E,14Z)-12-Hydroxy-5,8,10,14-eicosatetraenoic acid; 12(S)-HETE; 12(S)-Hydroxy-5(Z),8(Z),10(e),14(Z)-eicosatetraenoate; 12(S)-Hydroxy-5(Z),8(Z),10(e),14(Z)-eicosatetraenoic acid; 12(S)-Hydroxy-5,8,14(Z),10(e)-eicosatetraenoate; 12(S)-Hydroxy-5,8,14(Z),10(e)-eicosatetraenoic acid; 12(S)-Hydroxy-5,8,14-cis-10-trans-eicosatetraenoic acid; 12(S)-Hydroxyeicosatetraenoate; 12(S)-Hydroxyeicosatetraenoic acid; 12-Hydroxy-5,8,10,14-eicosatetraenoic acid; 12-Hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid; 12-Hydroxyeicosatetraenoic acid; 12-L-Hydroxy-5,8,10,14-eicosatetraenoic acid; 12S-HETE; 12S-Hydroxy-5,8,10,14-(Z,Z,e,Z)-eicosatetraenoic acid; FA(20:4(5Z,8Z,10E,12-OH,14Z)); FA(20:4(5Z,8Z,10E,12S-OH,14Z))
Source Endogenous;Fatty acyls;Food
Structure Type   Eicosanoids  (Click to Show/Hide the Complete Structure Type Hierarchy)
Lipids and lipid-like molecules
Fatty Acyls
Eicosanoids
PubChem CID
5283155
HMDB ID
HMDB0006111
Formula
C20H32O3
Structure
<iframe style="width: 300px; height: 300px;" frameborder="0" src="https://embed.molview.org/v1/?mode=balls&cid=5283155"></iframe>
3D MOL 2D MOL
  Click to Show/Hide the Molecular/Functional Data (External Links/Property/Function) of This Metabolite
KEGG ID
C14777
ChEBI ID
34146
Physicochemical Properties Molecular Weight 320.5 Topological Polar Surface Area 57.5
XlogP 5.2 Complexity 392
Heavy Atom Count 23 Rotatable Bond Count 14
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 3
Function
12-Hydroxyeicosatetraenoic acid (CAS: 71030-37-0), also known as 12-HETE, is an eicosanoid, a 5-lipoxygenase metabolite of arachidonic acid. 5-Lipoxygenase (LO)-derived leukotrienes are involved in inflammatory glomerular injury. LO product 12-HETE is associated with the pathogenesis of hypertension and may mediate angiotensin II and TGFbeta induced mesangial cell abnormality in diabetic nephropathy. 12-HETE is markedly elevated in the psoriatic lesions. 12-HETE is a vasoconstrictor eicosanoid that contributes to high blood pressure in (renovascular) hypertension and pregnancy-induced hypertension. A significant percentage of patients suffering from a selective increase in plasma LDL cholesterol (type IIa hyperlipoproteinemia) exhibits increased platelet reactivity. This includes enhanced platelet responsiveness against a variety of platelet-stimulating agents ex vivo and enhanced arachidonic acid metabolism associated with increased generation of arachidonic acid metabolites such as 12-HETE, and secretion of platelet-storage products. 12-HETE is a highly selective ligand used to label mu-opioid receptors in both membranes and tissue sections. The 12-S-HETE analog has been reported to augment tumour cell metastatic potential through activation of protein kinase C. 12-HETE has a diversity of biological actions and is generated by a number of tissues including the renal glomerulus and the vasculature. 12-HETE is one of the six monohydroxy fatty acids produced by the non-enzymatic oxidation of arachidonic acid. 12-HETE is a neuromodulator that is synthesized during ischemia. Its neuronal effects include attenuation of calcium influx and glutamate release as well as inhibition of AMPA receptor (AMPA-R) activation. 12-HETE is found to be associated with peroxisomal biogenesis defect and Zellweger syndrome, which are inborn errors of metabolism.
Regulatory Network
Full List of Protein(s) Regulated by This Metabolite
      GPCR rhodopsin (GPCR-1)
            G-protein coupled receptor 31 (GPR31) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation 12-HETE addition (1.50 hours)
                      Induced Change GPR31 protein expression levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that 12-HETE addition causes the increase of GPR31 protein expression compared with control group.
      Transcription regulator (TR)
            DNA-binding factor KBF1 (p105) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation 12-HETE addition (1.50 hours)
                      Induced Change NFKB1 protein expression levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that 12-HETE addition causes the increase of NFKB1 protein expression compared with control group.
            DNA-binding factor KBF2 (NFKB) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation 12-HETE addition (1.50 hours)
                      Induced Change NFKB2 protein expression levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that 12-HETE addition causes the increase of NFKB2 protein expression compared with control group.
      Transferases (EC 2)
            Signal-regulated kinase 1 (ERK1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation 12-HETE addition (0.08 hours)
                      Induced Change MAPK3 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that 12-HETE addition causes the increase of MAPK3 protein phosphorylation compared with control group.
            Signal-regulated kinase 2 (ERK2) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation 12-HETE addition (0.08 hours)
                      Induced Change MAPK1 protein phosphorylation levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that 12-HETE addition causes the increase of MAPK1 protein phosphorylation compared with control group.
Full List of Protein(s) Regulating This Metabolite
      Hydrolases (EC 3)
            Group 3 secretory phospholipase A2 (PLA2G3) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Knockout of Pla2g3
                      Induced Change 12-HETE concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockout of Pla2g3 leads to the decrease of 12-HETE levels compared with control group.
      Lyases (EC 4)
            Hydroperoxide isomerase ALOXE3 (eLOX-3) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Knockout of Aloxe3
                      Induced Change 12-HETE concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that knockout of Aloxe3 leads to the increase of 12-HETE levels compared with control group.
      Oxidoreductases (EC 1)
            Arachidonate 15-lipoxygenase B (ALOX15B) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [4]
                      Introduced Variation Overexpression of Alox15b
                      Induced Change 12-HETE concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of Alox15b leads to the increase of 12-HETE levels compared with control group.
References
1 Identification of the orphan G protein-coupled receptor GPR31 as a receptor for 12-(S)-hydroxyeicosatetraenoic acid. J Biol Chem. 2011 Sep 30;286(39):33832-40.
2 Group III secreted phospholipase A2 regulates epididymal sperm maturation and fertility in mice. J Clin Invest. 2010 May;120(5):1400-14.
3 Aloxe3 knockout mice reveal a function of epidermal lipoxygenase-3 as hepoxilin synthase and its pivotal role in barrier formation. J Invest Dermatol. 2013 Jan;133(1):172-80.
4 Systematic analysis of rat 12/15-lipoxygenase enzymes reveals critical role for spinal eLOX3 hepoxilin synthase activity in inflammatory hyperalgesia. FASEB J. 2013 May;27(5):1939-49.

If you find any error in data or bug in web service, please kindly report it to Dr. Zhang and Dr. Mou.