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Nitrogen Excretion and the Urea Cycle:-The Citric Acid and Urea Cycles Can Be Linked

المؤلف:  David L. Nelson، Michael M. Cox

المصدر:  Lehninger Principles of Biochemistry

الجزء والصفحة:  668

2026-06-14

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Nitrogen Excretion and the Urea Cycle:-The Citric Acid and Urea Cycles Can Be Linked

Because the fumarate produced in the argininosuccinase reaction is also an intermediate of the citric acid cycle, the cycles are, in principle, interconnected—in a process dubbed the “Krebs bicycle” (Fig. 18–12). How ever, each cycle can operate independently and communication between them depends on the transport of key intermediates between the mitochondrion and cy tosol. Several enzymes of the citric acid cycle, including fumarase (fumarate hydratase) and malate dehydrogenase, are also present as isozymes in the cytosol. The fumarate generated in cytosolic arginine synthesis can therefore be converted to malate in the cytosol, and these intermediates can be further metabolized in the cytosol or transported into mitochondria for use in the citric acid cycle. Aspartate formed in mitochondria by transamination between oxaloacetate and glutamate can be transported to the cytosol, where it serves as nitrogen donor in the urea cycle reaction catalyzed by argininosuccinate synthetase. These reactions, making up the aspartate-argininosuccinate shunt, provide metabolic links between the separate pathways by which the amino groups and carbon skeletons of amino acids are processed.

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 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.