title: Amino acid substitutions in the human glutathione S-transferases confer different specificities in the prostaglandin endoperoxide conversion pathway.
abstract: The human glutathione S-transferases 1-1 and 2-2, which differ from each other by 11 amino acids, have different catalytic activities against cumene hydroperoxide and t-butyl hydroperoxide. Using prostaglandin H2 as the peroxide substrate, we found that GSH S-transferase 1-1 catalyzed the transformation of prostaglandin H2 to prostaglandin F2 alpha and E2 at a 4:1 ratio whereas GSH S-transferase 2-2 produced primarily prostaglandin D2 and F2 alpha at a 4:1 ratio. Our results indicate that GSH S-transferases catalyze the reduction and isomerization of prostaglandin H2 endoperoxide in vitro. We suggest that the amino acid substitutions between these two isozymes may be responsible for the difference in catalytic specificities. We propose that these isozymes are important reagents for the biosynthesis of various prostaglandins.
authors.affiliation: Department of Veterinary Science, Pennsylvania State University, University Park 16802.
authors.forename: J R
authors.initials: JR
authors.lastname: Burgess
authors.forename: N W
authors.initials: NW
authors.lastname: Chow
authors.forename: C C
authors.initials: CC
authors.lastname: Reddy
authors.forename: C P
authors.initials: CP
authors.lastname: Tu
mesh_terms: D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D011449:Prostaglandin Endoperoxides / Q000378:metabolism*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000378:metabolism; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D007527:Isoenzymes; D011449:Prostaglandin Endoperoxides; D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; D044262:Prostaglandin H2; D015237:Dinoprost; D005982:Glutathione Transferase; D015232:Dinoprostone