The most important objective in this research is to study the metabolism of N?G?-monomethyl-L-arginine, an endogenously synthesized compound, and to identify one of the metabolites as N-methylurea, a compound which can be nitrosated to give rise to 1-N-methyl,1-N-nitrosourea, one of the most potent carcinogens known. This will be pursued with the following aims: (1) to study the metabolic pathways of N?G?-monomethyl-L-arginine which involve hydrolytic cleavage, oxidative demethylation, and decarboxylation; (2) to investigate the possible formation of N-methylurea from N?G?-monomethyl-L-arginine; (3) to further purify protein methylase I which methylates the guanadine group of protein-bound arginine residues; and (4) to investigate the possible antitumor effects of N?G?-monomethyl-L-arginine on tumor cells in tissue or cell culture. (K)
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