Nitrogen Excretion and the Urea Cycle:- Pathway Interconnections Reduce the Energetic Cost of Urea Synthesis
If we consider the urea cycle in isolation, we see that the synthesis of one molecule of urea requires four high energy phosphate groups (Fig. 18–10). Two ATP molecules are required to make carbamoyl phosphate, and one ATP to make argininosuccinate—the latter ATP undergoing a pyrophosphate cleavage to AMP and PPi, which is hydrolyzed to two Pi. The overall equation of the urea cycle is
2NH4++HCO3-+3ATP-4+H2O→urea+2ADP3+4Pi-2+AMP2-+2H+
However, the urea cycle also causes a net conversion of oxaloacetate to fumarate (via aspartate), and the re generation of oxaloacetate (Fig. 18–12) produces NADH in the malate dehydrogenase reaction. Each NADH molecule can generate up to 2.5 ATP during mitochondrial respiration, greatly reducing the overall energetic cost of urea synthesis.
FIGURE 18–12 Links between the urea cycle and citric acid cycle. The interconnected cycles have been called the “Krebs bicycle.” The pathways linking the citric acid and urea cycles are called the aspartate-argininosuccinate shunt; these effectively link the fates of the amino groups and the carbon skeletons of amino acids. The inter connections are even more elaborate than the arrows suggest. For Mitochondrial matrix Ornithine Carbamoyl phosphate Cytosol example, some citric acid cycle enzymes, such as fumarase and malate dehydrogenase, have both cytosolic and mitochondrial isozymes. Fumarate produced in the cytosol—whether by the urea cycle, purine biosynthesis, or other processes—can be converted to cytosolic malate, which is used in the cytosol or transported into mitochondria (via the malate-aspartate shuttle; see Fig. 19–27) to enter the citric acid cycle.
