ABSTRACT
Nitrogen is incorporated into a cell’s metabolism in several oxidation states including NH4+ , NO3-, N2, as well as through urea and amino acids, and purine and pyrimidine metabolites, however the most common route for utilization of inorganic nitrogen is generally ammonia. Reactions involving nitrogen assimilation in all organisms lead to the formation of central nitrogen carriers, primarily glutamate, and glutamine, and to a lesser extent the secondary metabolites aspartate and carbamoyl phosphate. Carbamoyl phosphate is unique in that it is only utilized for the biosynthesis of arginine, urea, and pyrimidine nucleotides. As such most nitrogen transfer from ammonia to the amino acids and other nitrogen containing molecules is conducted through the two primary nitrogen carriers’ glutamate and glutamine. By and large, the process from substrate uptake to cellular component synthesis using nitrogen is carried out in three steps. First, and only aer nitrogen sources from the environment are transported into the cells, ammonia formation occurs through the reduction of nitrite or N2 or by hydrolytic release mechanisms from nitrogen containing organic substrates. e second step involves nitrogen transfer, in which case, the ammonia is transferred to form glutamate and glutamine. Glutamine is the direct nitrogen donor for most nitrogen containing building blocks, except for the α-amino group of the amino acids for which glutamine is only an indirect donor, where glutamate on the other hand, is the universal amino donor of α-amino acids. In E. coli ammonia assimilation is conducted through glutamine synthesis mediated by L-glutamine synthetase when not under energy limitation or by a glutamate dehydrogenase (GDH) pathway when energy in the cell is at a premium and phosphate levels are high. e GDH pathway is the primary ammonia assimilation route in fungi and yeast. In the third step, nitrogen is nally released by transferring the α-amino group of L-glutamate to 2-oxo acids, the direct precursors of α-amino acids, by aminotransferase enzymes. In general, most cell types possess a variety of aminotransferases in which each enzyme is uniquely responsible for the synthesis of a group of 2-oxo acids.
