title: Inhibitory effects in vitro of S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-glutathione, a proposed metabolite of L-histidine, on gamma-glutamyltransferase activity.
abstract: A transfer of the gamma-glutamyl moiety of S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]glutathione (I), an adduct of glutathione and L-histidine metabolite urocanic acid, has been investigated by using gamma-glutamyltransferase preparation from bovine kidney. When an equimolar mixture of two diastereomers of compound I in a phosphate buffer was allowed to react with glycylglycine in the presence of the transferase, two diastereomers of N-[S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-L-cysteinyl]glycine (II) were formed in the same yield with each other and this was accompanied by a formation of gamma-glutamylglycylglycine. Kinetics of compound I with the transferase indicated high affinity between the two materials, while the maximal reaction velocity of the gamma-glutamyl transfer was low. Effects of compound I in vitro on the transfer of gamma-glutamyl moiety of gamma-glutamyl-p-nitroanilide to glycylglycine with the transferase were also studied, and the results indicated that the transfer was suppressed by compound I based on its competitive and non-competitive inhibitions. These results suggest that little variation in reactivities of two diastereomers of compound I as the substrate is given by the difference in stereomerism of their asymmetric carbon atoms and that inhibitory effects of compound I on the catalytic action of the transferase is of sufficient physiological importance to decrease the degradation of natural gamma-glutamyl compounds, such as glutathione and its analogs.
authors.affiliation: Department of Biochemistry, Okayama University Medical School, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Shimizu
authors.forename: M
authors.initials: M
authors.lastname: Kinuta
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006639:Histidine / Q000378:metabolism*; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D013237:Stereoisomerism; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; C081579:S-(2-carboxy-1-(1H-imidazol-4-yl)ethyl)glutathione; D006639:Histidine; D005723:gamma-Glutamyltransferase; D005978:Glutathione