Argininosuccinase, urea cycle

The synthesis of fumarate by argininosuccinase links the urea cycle to the citric acid cycle (Fig. 2). Fumarate is an intermediate of this latter cycle which is then hydrated to malate, which in turn is oxidized to oxaloacetate (see Topic LI). 

The enzymes that catalyze these steps are homologous to argininosuccinate synthetase and argininosuccinase, respectively. Thus, four of the five enzymes in the urea cycle were adapted from enzymes taking part in nucleotide biosynthesis. The remaining enzyme, arginase, appears to be an ancient enzyme found in all domains of life. 

An inborn error of metabolism which is due to a deficiency of the urea cycle enzyme argininosuccinase. Argininosuccinic acid and ammonia accumulate and the symptoms include mental retardation and hepatomegaly. 

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