Metabolic recycling of ammonia via glutamate dehydrogenase supports breast cancer biomass

Abstract

Cancer cells put ammonia back to work Ammonia, often considered a metabolic waste product, can be recycled to build new amino acids. Rapidly proliferating cells produce extracellular nitrogen. Spinelli et al. used metabolic tracing of 15 N to follow the fate of extracellular ammonia and its incorporation into more than 200 components of the nitrogen metabolome (see the Perspective by Dang). Accumulation of ammonia enabled glutamate dehydrogenase to function in reductive amination, which allowed incorporation of nitrogen from ammonia back into amino acids. Experiments in mice also showed incorporation of ammonia into glutamate, aspartate, and proline. Science , this issue p. 941 ; see also p. 862