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Formation of S ‐[2‐carboxy‐1‐(1 H ‐imidazol‐4‐yl) ethyl]glutathione, a new metabolite of L ‐histidine, from cis ‐urocanic acid and glutathione by the action of glutathione S ‐transferase
Author(s) -
Kinuta Masahiro,
Kinuta Keiko,
Yamada Hiroshi,
Abe Tadashi,
Yoshida Yumi,
Araki Kenta,
Li ShunAi,
Otsuka Atsushi,
Nakanishi Akira,
Moriyama Yoshinori,
Takei Kohji
Publication year - 2003
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.200305582
Subject(s) - urocanic acid , chemistry , glutathione , metabolite , adduct , histidine , cysteine , stereochemistry , enzyme , biochemistry , organic chemistry
Exposure of the skin to sunlight results in an increase of the content of epidermal trans ‐urocanic acid, a key metabolite of L ‐histidine, and also in occurrence of the isomerization of trans ‐urocanic acid to the cis isomer. S ‐[2‐Carboxy‐1‐(1 H ‐imidazol‐4‐yl)ethyl]glutathione (GS(CIE)), an adduct of urocanic acid and glutathione, is a presumed origin of a urinary compound S ‐[2‐carboxy‐1‐(1 H ‐imidazol‐4‐yl)ethyl]‐ L ‐cysteine (Cys(CIE)). The formation of GS(CIE) is stimulated by exposing the skin to sunlight irradiation. In this study we investigated an enzymatic formation of GS(CIE) from glutathione and cis ‐urocanic acid by incubation with rat liver extract that contained glutathione S ‐transferase (GST) at high activity. The formation of GS(CIE) was suppressed significantly when a liver extract depleted of GST activity was used. Enzymatic degradation of GS(CIE) with γ ‐glutamyl transpeptidase resulted in the formation of N ‐{ S ‐[2‐carboxy‐1‐(1 H ‐imidazol‐4‐yl)ethyl]‐ L ‐cysteinyl}glycine, a metabolic intermediate between the glutathione adduct and Cys(CIE). A hydrolyzed product of GS(CIE) by HCl was identical with the urinary Cys(CIE). Compounds were analyzed by high‐voltage paper electrophoresis, capillary electrophoresis, and fast atom bombardment mass spectrometry. From these results, we suggest that GS(CIE) formed from cis ‐urocanic acid and glutathione is an origin of the urinary compound Cys(CIE) and that the formation reaction is catalyzed mostly by the action of GST.