Cytidine triphosphate ATCase inhibition

Perhaps the best-studied regulatory enzyme of this kind is aspartate transcarbamoy-lase (ATCase), which catalyzes the first steps in the biosynthetic pathway leading to uridine and cytidine nucleotides. Today, a great amount of information, structural, thermodynamical, and kinetic, is available on this system. Specifically it is known that cytidine triphosphate (CTP) inhibits ATCase. (Other molecules, such as ATP, activate the same enzyme. We shall focus, in this section, on inhibitory effectors only.)... 

Figure 10.2. CTP luhibits ATCase. Cytidine triphosphate, an end product of the pyrimidine synthesis pathway, inhibits aspartate transcarbamoylase despite having little structural similarity to reactants or products.

In this experiment we will examine some of the properties of the aspartate transcarbamylase of Escherichia coli, which is typical of many enzymes subject to feedback inhibition and which has been studied extensively. Aspartate transcarbamylase (ATCase) catalyzes the first reaction unique to the biosynthesis of pyrimidine nucleotides. ATCase is subject to specific inhibition by quite low concentrations of one of its end products, cytidine 5 -triphosphate (CTP). This relationship and two other regulatory interactions important to the control of pyrimidine biosynthesis are summarized in Figure 9-1. 

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