In the first reaction, NH4+ + HCO3− is equivalent to NH3 + CO2 + H2O.
Thus, the overall equation of the urea cycle is:
NH3 + CO2 + aspartate + 3 ATP + 2 H2O → urea + fumarate + 2 ADP + 2 Pi + AMP + PPi
Since fumarate is obtained by removing NH3 from aspartate (by means of reactions 3 and 4), and PPi + H2O → 2 Pi, the equation can be simplified as follows:
2 NH3 + CO2 + 3 ATP + H2O → urea + 2 ADP + 4 Pi + AMP
Note that reactions related to the urea cycle also cause the production of 2 NADH, so the urea cycle releases slightly more energy than it consumes. These NADH are produced in two ways:
One NADH molecule is reduced by the enzyme glutamate dehydrogenase in the conversion of glutamate to ammonium and α-ketoglutarate. Glutamate is the non-toxic carrier of amine groups. This provides the ammonium ion used in the initial synthesis of carbamoyl phosphate.
The fumarate released in the cytosol is converted to malate by cytosolic fumarase. This malate is then converted to oxaloacetate by cytosolic malate dehydrogenase, generating a reduced NADH in the cytosol. Oxaloacetate is one of the keto acids preferred by transaminases, and so will be recycled to aspartate, maintaining the flow of nitrogen into the urea cycle.
The two NADH produced can provide energy for the formation of 4 ATP (cytosolic NADH provides only 1.5 ATP due to the glycerol-3-phosphate shuttle who transfers the electrons from cytosolic NADH to FADH2 and that gives 1.5 ATP), a net production of one high-energy phosphate bond for the urea cycle. However, if gluconeogenesis is underway in the cytosol, the latter reducing equivalent is used to drive the reversal of the GAPDH step instead of generating ATP.
The fate of oxaloacetate is either to produce aspartate via transamination or to be converted to phosphoenolpyruvate, which is a substrate for gluconeogenesis.