Targeting Arg metabolism. Arg can be synthesized from other amino acids via urea cycle; however, tumor cells lacking the urea cycle enzyme arginosuccinate synthetase (ASS) rely on exogenous supply of Arg. The endogenous sources of Arg can be used as a potential therapeutic intervention in treating cancer. ADI catalyzes Arg degradation to citrulline and ammonium. ARGase generates ornithine as an intermediate, and ornithine carbomoyltransferase (OTC) catalyzes the conversion of ornithine to citrulline. Upon condensation of Asp and citrulline by the enzymatic activity of ASS, arginosuccinate intermediate is generated followed by the reformation of Arg.