| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
In the skin, only trans-urocanic acid is formed from L-histidine by histidine ammonia-lyase and then accumulated in epidermis because of the absence of urocanate hydratase from the skin. The epidermal urocanic acid isomerized to the cis isomer by ultraviolet light. However, physiological functions of the accumulation and of the isomerization have not been elucidated. This research deals with a new pathway of urocanic acid metabolism, which is initiated by the adduction of glutathione to urocanic acid to form a glutathione S-conjugated imidazole compound (I), and also with its physiological roles. We previously suggested that the metabolism related to the trans-cis isomerization and the elimination of the epidermal urocanic acid under conditions of sunlight irradation. New knowledges and results obtained are as follows : 1, Three additional metabolites of compound I were specified, and the new metabolic pathway has been established completely ; 2, Compound I and its metabolites located in the pathway have an asymmetric beta-carbon atom on the skeletal imidazolepropanoate part of their molecules, i.e., the existance of two diastereomers of each metabolite ; 3, The two diastereomers of each metabolite were prepared, purified by ion-exchangers, and characterizad by physicochemical analyzes ; 4, A new method for simultaneous determination of the diastereomers was developed by capillary electrophoresis, and this method achieved characterization of the enzymatic recognition of stereoisomerism on the beta-carbon atom of their molecules ; 5, A great inhibitory effect of compound I on gamma-glutamyltransferase activity was elucidated and this involves a physiological importance of the formation of compound I under conditions of sunlight irradiation probably to increase intracellular and/or extracellular levels of glutathione, and to protect from oxidative stresses or damages in tissues caused by sunlight.
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