Ophthalmate biosynthesis in hepatocytes (WP4487)

Homo sapiens

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This pathway visualises the mechanism of ophthalmate biosynthesis in hepatocytes. GSH can inhibits GCC; however when the cell is facing oxidative stress, GSH is consumed, and therefore activating GCS. This enhances the biosynthesis of ophthalmate, which is transported out of the cell over the hepatocellular membrane via MRP transporters.

Authors

Denise Slenter , Egon Willighagen , Martina Summer-Kutmon , and Eric Weitz

Activity

last edited

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

glutathione metabolic pathway

Cell Type Ontology

hepatocyte

Participants

Label Type Compact URI Comment
Cys Metabolite wikidata:Q186474
Gamma-Glu-Cys Metabolite wikidata:Q288236
GSH Metabolite wikidata:Q116907 aka glutathione
2AB Metabolite wikidata:Q27104317 aka 2-aminobutyrate
Gamma-Glu-2AB Metabolite pubchem.compound:78437958 aka gamma-Glutamyl-2-aminobutyrate
Ophthalmate Metabolite ttd.drug:Q7098084 aka ophthalmic acid
Ophthalmate Metabolite wikidata:Q7098084 aka ophthalmic acid
GCS Protein eccode:6.3.2.2 aka Glutamate Cysteine Ligase (GCL) (EC 6.3.2.2), previously known as gamma-glutamylcysteine synthetase (GCS)
GS Protein eccode:6.3.2.3 aka Glutathione synthetase (GSS)

References

  1. Glutathione synthetase. Purification from rat kidney and mapping of the substrate binding sites. Oppenheimer L, Wellner VP, Griffith OW, Meister A. J Biol Chem. 1979 Jun 25;254(12):5184–90. PubMed Europe PMC Scholia
  2. Synthesis of ophthalmic acid in liver and kidney in vivo. Orlowski M, Wilk S. Biochem J. 1978 Feb 15;170(2):415–9. PubMed Europe PMC Scholia
  3. On the active site thiol of gamma-glutamylcysteine synthetase: relationships to catalysis, inhibition, and regulation. Huang CS, Moore WR, Meister A. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2464–8. PubMed Europe PMC Scholia
  4. Differential metabolomics reveals ophthalmic acid as an oxidative stress biomarker indicating hepatic glutathione consumption. Soga T, Baran R, Suematsu M, Ueno Y, Ikeda S, Sakurakawa T, et al. J Biol Chem. 2006 Jun 16;281(24):16768–76. PubMed Europe PMC Scholia