Editing Urea cycle (section)

=== Overall reaction equation ===
In the first reaction, {{chem|NH|4|+}} + {{chem|HCO|3|-}} is equivalent to [[Ammonia|NH<sub>3</sub>]] + [[Carbon dioxide|CO<sub>2</sub>]] + [[Water|H<sub>2</sub>O]].

Thus, the overall equation of the urea cycle is:
* [[Ammonia|NH<sub>3</sub>]] + [[Carbon dioxide|CO<sub>2</sub>]] + [[aspartate]] + 3 [[Adenosine triphosphate|ATP]] + 3 [[Water|H<sub>2</sub>O]] → [[urea]] + [[fumarate]] + 2 [[Adenosine diphosphate|ADP]] + 2 [[Phosphate|P<sub>i</sub>]] + [[Adenosine monophosphate|AMP]] + [[Pyrophosphate|PP<sub>i</sub>]] + [[Water|H<sub>2</sub>O]]
Since fumarate is obtained by removing NH<sub>3</sub> from aspartate (by means of reactions 3 and 4), and PP<sub>i</sub> + H<sub>2</sub>O → 2 P<sub>i</sub>, the equation can be simplified as follows:
* 2 [[Ammonia|NH<sub>3</sub>]] + [[Carbon dioxide|CO<sub>2</sub>]] + 3 [[Adenosine triphosphate|ATP]] + 3 [[Water|H<sub>2</sub>O]] → [[urea]] + 2 [[Adenosine diphosphate|ADP]] + 4 [[Phosphate|P<sub>i</sub>]] + [[Adenosine monophosphate|AMP]]
Note that reactions related to the urea cycle also cause the production of 2 [[NADH]], so the overall reaction releases slightly more energy than it consumes. The NADH is produced in two ways:
* One NADH molecule is produced 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 hydrated to [[malate]] by cytosolic [[fumarase]]. This malate is then oxidized to [[oxaloacetate]] by cytosolic [[malate dehydrogenase]], generating a reduced NADH in the cytosol. [[Oxaloacetate]] is one of the keto acids preferred by [[transaminase]]s, and so will be recycled to [[aspartate]], maintaining the flow of nitrogen into the urea cycle.
We can summarize this by combining the reactions:
* CO<sub>2</sub> + [[glutamate]] + [[aspartate]] + 3 ATP + 2 NAD<sup>+</sup>+ 3 H<sub>2</sub>O → [[urea]] + [[α-ketoglutarate]] + [[oxaloacetate]] + 2 ADP + 2 P<sub>i</sub> + AMP + PP<sub>i</sub> + 2 NADH
The two NADH produced can provide energy for the formation of 5 [[Adenosine triphosphate|ATP]] (cytosolic NADH provides 2.5 ATP with the malate-aspartate shuttle in human liver cell), a net production of two 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 [[Phosphoenolpyruvic acid|phosphoenolpyruvate]], which is a substrate for [[gluconeogenesis]].<!--
An excellent way to memorize the Urea Cycle is to remember the [[mnemonic]] phrase "Ordinarily Careless Crappers Are Also Frivolous About Urination." The first letter of each word corresponds to the first letter of each of the main reactants or products that are combined with each other or produced as one progresses through the five reactions of the cycle (Ornithine, Carbamoyl phosphate, Citrulline, Aspartate, Argininosuccinate, Fumarate, Arginine, Urea).-->