Glutathione conjugation

Summary
Organism
Homo sapiens (human)
Reactome
R-HSA-156590
PubChem
R-HSA-156590
Description
  • Glutathione S-Transferases (GSTs; EC 2.5.1.18) are another major set of phase II conjugation enzymes. They can be found in the cytosol as well as being microsomal membrane-bound. Cytosolic GSTs are encoded by at least 5 gene families (alpha, mu, pi, theta and zeta GST) whereas membrane-bound enzymes are encoded by single genes. Soluble GSTs are homo- or hetero-dimeric enzymes (approximately 25KDa subunits) which can act on a wide range of endogenous and exogenous electrophiles. GSTs mediate conjugation using glutathione (GSH), a tripeptide synthesized from its precursor amino acids gamma-glutamate, cysteine and glycine. A generalized reaction is

    RX + GSH -> HX + GSR

    Glutathione conjugates are excreted in bile and converted to cysteine and mercapturic acid conjugates in the intestine and kidneys. GSH is the major, low molecular weight, non-protein thiol synthesized de novo in mammalian cells. As well as taking part in conjugation reactions, GSH also has antioxidant ability and can metabolize endogenous and exogenous compounds. The nucleophilic GSH attacks the electrophilic substrate forming a thioether bond between the cysteine residue of GSH and the electrophile. The result is generally a less reactive and more water-soluble conjugate that can be easily excreted. In some cases, GSTs can activate compounds to reactive species such as certain haloalkanes and haloalkenes. Substrates for GSTs include epoxides, alkenes and compounds with electrophilic carbon, sulfur or nitrogen centres. There are two types of conjugation reaction with glutathione: displacement reactions where glutathione displaces an electron-withdrawing group and addition reactions where glutathione is added to activated double bond structures or strained ring systems.
Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.
Displaying all 5 entries
UniProt ID Protein Name Gene Symbol Pathway Viewer
O60760 Hematopoietic prostaglandin D synthase
  • GSTS
  • HPGDS
  • PGDS
  • PTGDS2
view
P0CG30 Glutathione S-transferase theta-2B
  • GSTT2
  • GSTT2B
view
P10768 S-formylglutathione hydrolase
  • ESD
view
P28161 Glutathione S-transferase Mu 2
  • GST4
  • GSTM2
view
P78417 Glutathione S-transferase omega-1
  • GSTO1
  • GSTTLP28
view

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Acknowledgements

Supported by JST NBDC Grant Number JPMJND2204

Partly supported by NIH Common Fund Grant #1U01GM125267-01


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Last updated: April 6, 2026