Aspartate Carbamoyl Transferase Allosteric Control of Pyrimidine Biosynthesis

Aspartate Carbamoyl Transferase Allosteric Control of Pyrimidine Biosynthesis 

The behavior of aspartate carbamoylase changed dramatically when the enzyme was treated with the organic mercurial compound p-hydroxymercuribenzoate (see fig. 9.14). The binding of aspartate no longer showed positive cooperativity, and ATP or CTP were without effect. Exposure to mercurials was found to cause the enzyme to dissociate into two types of fragments, one of which retained the enzymatic activity but was no longer affected by CTP or 

Effects of CTP, ATP, and mercurials on the rate of the reaction catalyzed by aspartate carbamoyl transferase. In the absence of CTP and ATP, the sigmoidal kinetics show positive cooperativity with respect to aspartate. CTP augments the positive cooperativity ATP reverses the effect of CTP. An organic mercurial, or ATP in the absence of CTP, eliminates the cooperativity, converting the curve from sigmoidal to hyperbolic. 

Subunit structure of aspartate carbamoyl transferase and the fragments produced by treating the enzyme with mercurials. In the complete enzyme (top), the three sets of regulator dimers are sandwiched between two trimers of catalytic subunits (see fig. 9.17). The approximate location of the active site in each c subunit of the trimer facing the viewer is indicated with a c. 

The changes in sedimentation coefficient and chemical reactivity caused by PALA fit the model that the enzyme exists in two distinct conformations (T and R) and that the binding of PALA to only one or two of the c subunits causes the entire c6r6 complex to flip from the T to the R state. The dissociation constant for PALA is higher in the T state than in the R state. The equilibrium constant L = [T]/[R] has been calculated to be 250 in the absence of substrates and 

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Allosteric Enzymes Typically Exhibit a Sigmoidal Dependence on Substrate Concentration The Symmetry Model Provides a Useful Framework for Relating Conformational Transitions to Allosteric Activation or Inhibition Phosphofructokinase Allosteric Control of Glycolysis Is Consistent with the Symmetry Model Aspartate Carbamoyl Transferase Allosteric Control of Pyrimidine Biosynthesis Glycogen Phosphorylase Combined Control by Allosteric Effectors and Phosphorylation... 

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