Nitrogen-saving strategies used by transformed cells to mitigate the deficit of reduced nitrogen carriers in the tumor microenvironment. (A) De novo glutamine synthesis; (B) Preference for transamination of glutamate to α-ketoglutarate as a strategy to maximize non-essential amino acid synthesis in proliferating cells; (C) De novo glutamate synthesis; (D) Preference for CPS-I-mediated route of carbamoyl-phosphate production in LKB1-deificient tumors; (E) Increased availability of aspartate for pyrimidine synthesis coupled to an increased reliance on arginine import in ASS1-deficient tumors. GLUL; glutamate-ammonia ligase (glutamine synthetase); GDH1, glutamate dehydrogenase 1; CAD, carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase; CPS-I, carbamoyl phosphate synthetase I; ASS1, argininosuccinate synthetase 1.