Formation of S-[2-carboxy-1-(1H-imidazol-4-yl) ethyl]glutathione, a new metabolite of L-histidine, from cis-urocanic acid and glutathione by the action of glutathione S-transferase.
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-(1H-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-(1H-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 gamma -glutamyl transpeptidase resulted in the formation of N-[S-[2-carboxy-1-(1H-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.
D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives / Q000652:urine; D019075:Electrophoresis, Capillary; D004590:Electrophoresis, Paper; D005978:Glutathione / Q000031:analogs & derivatives* / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D005982:Glutathione Transferase / Q000172:deficiency / Q000378:metabolism*; D006639:Histidine / Q000378:metabolism*; D007093:Imidazoles / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism / Q000528:radiation effects; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013237:Stereoisomerism; D013472:Sunlight; D014560:Urocanic Acid / Q000378:metabolism*
D007093:Imidazoles; C081579:S-(2-carboxy-1-(1H-imidazol-4-yl)ethyl)glutathione; D006639:Histidine; D005982:Glutathione Transferase; D014560:Urocanic Acid; D005978:Glutathione; D003545:Cysteine