Determination of S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]glutathione, a novel metabolite of L-histidine, in tissue extracts from sunlight-irradiated rat by capillary electrophoresis

Exposure of the skin to sunlight results in an increase in the content of e pidermal Urocanic acid, a key metabolite Of L-histidine, and some portions of the metabolite penetrate into the body fluid. S-[2-Carboxy-1 -(1H-imidaz ol-4-yl)ethyl]glutathione (GS(CIE)), an adduct of glutathione and urocanic acid, was proposed to be an origin of a urinary compound, S-[2-carboxy-1-(1 H-imidazol-4-yl)ethyl]-L-cysteine (Cys(CIE)). Various catabolites of Cys(CI E) were also isolated from human urine previously. However, no direct evide nce to show the existence of GS(CIE) as a biological material had been foun d. By using capillary electrophoresis, the glutathione adduct has now been found in the extracts of rat tissues from the kidney, liver, skin and blood when the rat was kept under conditions of sunlight irradiation after the f ur on the dorsal skin had been clipped. On the other hand, no or a trace of GS(CIE) was determined in rat tissue extracts when the animal was kept ind oor in usual manner. The glutathione adduct was isolated from the kidney ex tract of the sunlight-irradiated rat using ion-exchangers and high-voltage paper electrophoresis, and determined by fast-atom-bombardment mass spectro metry. These results indicate that GS(CIE) formation actually occurs in the body and that the formation is accelerated by exposing the rat to sunlight irradiation. From these findings, we propose an alternative pathway of his tidine metabolism which is initiated by the adduction of urocanic acid to g lutathione to form GS(CIE) and terminates with the formation of the urinary compounds via Cys(CIE).