Enzymes
| UniProtKB help_outline | 2,308 proteins |
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- Name help_outline 15-deoxy-Δ12,14-prostaglandin J2 Identifier CHEBI:85236 Charge -1 Formula C20H27O3 InChIKeyhelp_outline VHRUMKCAEVRUBK-GODQJPCRSA-M SMILEShelp_outline CCCCC\C=C\C=C1/[C@@H](C\C=C/CCCC([O-])=O)C=CC1=O 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline glutathione Identifier CHEBI:57925 Charge -1 Formula C10H16N3O6S InChIKeyhelp_outline RWSXRVCMGQZWBV-WDSKDSINSA-M SMILEShelp_outline [NH3+][C@@H](CCC(=O)N[C@@H](CS)C(=O)NCC(=O)[O-])C(=O)[O-] 2D coordinates Mol file for the small molecule Search links Involved in 104 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 15-deoxy-Δ12,14-prostaglandin J2-S-(R)-glutathione Identifier CHEBI:194498 Charge -2 Formula C30H43N3O9S InChIKeyhelp_outline PJVSKAKTGJJITI-YPYHUWNQSA-L SMILEShelp_outline C1(CC(/C(/[C@H]1C/C=C\CCCC([O-])=O)=C/C=C/CCCCC)=O)SC[C@H](NC(CC[C@H]([NH3+])C(=O)[O-])=O)C(=O)NCC(=O)[O-] 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:75963 | RHEA:75964 | RHEA:75965 | RHEA:75966 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Publications
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Biosynthesis of prostaglandin 15dPGJ2 -glutathione and 15dPGJ2-cysteine conjugates in macrophages and mast cells via MGST3.
Steinmetz-Spaeh J., Liu J., Singh R., Ekoff M., Boddul S., Tang X., Bergqvist F., Idborg H., Heitel P., Roennberg E., Merk D., Wermeling F., Haeggstroem J.Z., Nilsson G., Steinhilber D., Larsson K., Korotkova M., Jakobsson P.J.
Inhibition of microsomal prostaglandin E synthase-1 (mPGES-1) results in decreased production of proinflammatory PGE<sub>2</sub> and can lead to shunting of PGH<sub>2</sub> into the prostaglandin D<sub>2</sub> (PGD<sub>2</sub>)/15-deoxy-Δ<sup>12,14</sup>-prostaglandin J<sub>2</sub> (15dPGJ<sub>2</ ... >> More
Inhibition of microsomal prostaglandin E synthase-1 (mPGES-1) results in decreased production of proinflammatory PGE<sub>2</sub> and can lead to shunting of PGH<sub>2</sub> into the prostaglandin D<sub>2</sub> (PGD<sub>2</sub>)/15-deoxy-Δ<sup>12,14</sup>-prostaglandin J<sub>2</sub> (15dPGJ<sub>2</sub>) pathway. 15dPGJ<sub>2</sub> forms Michael adducts with thiol-containing biomolecules such as GSH or cysteine residues on target proteins and is thought to promote resolution of inflammation. We aimed to elucidate the biosynthesis and metabolism of 15dPGJ<sub>2</sub> via conjugation with GSH, to form 15dPGJ<sub>2</sub>-glutathione (15dPGJ<sub>2</sub>-GS) and 15dPGJ<sub>2</sub>-cysteine (15dPGJ<sub>2</sub>-Cys) conjugates and to characterize the effects of mPGES-1 inhibition on the PGD<sub>2</sub>/15dPGJ<sub>2</sub> pathway in mouse and human immune cells. Our results demonstrate the formation of PGD<sub>2</sub>, 15dPGJ<sub>2</sub>, 15dPGJ<sub>2</sub>-GS, and 15dPGJ<sub>2</sub>-Cys in RAW264.7 cells after lipopolysaccharide stimulation. Moreover, 15dPGJ<sub>2</sub>-Cys was found in lipopolysaccharide-activated primary murine macrophages as well as in human mast cells following stimulation of the IgE-receptor. Our results also suggest that the microsomal glutathione S-transferase 3 is essential for the formation of 15dPGJ<sub>2</sub> conjugates. In contrast to inhibition of cyclooxygenase, which leads to blockage of the PGD<sub>2</sub>/15dPGJ<sub>2</sub> pathway, we found that inhibition of mPGES-1 preserves PGD<sub>2</sub> and its metabolites. Collectively, this study highlights the formation of 15dPGJ<sub>2</sub>-GS and 15dPGJ<sub>2</sub>-Cys in mouse and human immune cells, the involvement of microsomal glutathione S-transferase 3 in their biosynthesis, and their unchanged formation following inhibition of mPGES-1. The results encourage further research on their roles as bioactive lipid mediators. << Less