Urea Cycle: Overall Stoichiometry

Because four high-energy phosphate bonds are consumed in the synthesis of each molecule of urea, the synthesis of urea is irreversible, with a large, negative ΔG. One nitrogen of the urea molecule is supplied by free ammonia and the other nitrogen by aspartate. Glutamate is the immediate precursor of both ammonia (through oxidative deamination by GDH) and aspartate nitrogen  (through transamination of oxaloacetate by AST). In effect, both nitrogen atoms of urea arise from glutamate, which, in turn, gathers nitrogen from other amino acids (Fig. 1).

Figure 1:  Flow of nitrogen from amino acids to urea. Amino groups for urea synthesis are collected in the form of ammonia (NH₃) and aspartate. NAD(H) = nicotinamide adenine dinucleotide; HCO₃ ^– = bicarbonate.