Nitrogen Metabolism in Cancer and Immunity

Transaminases and deaminases regulate nitrogen availability for various biosynthetic pathways and are often altered to support the growth of cancer and immune cells. Glutamine and glutamate, which are the major reservoirs of nitrogen in cells, are used as nitrogen donors for synthesizing many nitrogenous compounds in both cancer and immune cells. Ammonia, liberated during deamination reactions, can be recycled by glutamine synthetase (GS), glutamate dehydrogenase (GDH), and carbamoyl phosphate synthetase (CPS) in cancer cells; however, whether such metabolic adaptation exists in other cell types remains largely unknown. The circuits that control the acquisition and maintenance of cellular nitrogen are often rewired at multiple levels in cancer and immune cells. Each cell type within the tumor microenvironment has a unique requirement for nitrogen sources. Expression of specific transaminases for nonessential AA synthesis are differentially regulated in cancer and T cells during AA deficiency. As one of the fundamental requirements for cell growth and proliferation, nitrogen acquisition and utilization must be tightly regulated. Nitrogen can be generated from amino acids (AAs) and utilized for biosynthetic processes through transamination and deamination reactions. Importantly, limitations of nitrogen availability in cells can disrupt the synthesis of proteins, nucleic acids, and other important nitrogen-containing compounds. Rewiring cellular metabolism to support anabolic processes is a feature common to both cancer and proliferating immune cells. In this review, we discuss how nitrogen is utilized in biosynthetic pathways and highlight different metabolic and oncogenic programs that alter the flow of nitrogen to sustain biomass production and growth, an important emerging feature of cancer and immune cell proliferation. As one of the fundamental requirements for cell growth and proliferation, nitrogen acquisition and utilization must be tightly regulated. Nitrogen can be generated from amino acids (AAs) and utilized for biosynthetic processes through transamination and deamination reactions. Importantly, limitations of nitrogen availability in cells can disrupt the synthesis of proteins, nucleic acids, and other important nitrogen-containing compounds. Rewiring cellular metabolism to support anabolic processes is a feature common to both cancer and proliferating immune cells. In this review, we discuss how nitrogen is utilized in biosynthetic pathways and highlight different metabolic and oncogenic programs that alter the flow of nitrogen to sustain biomass production and growth, an important emerging feature of cancer and immune cell proliferation.