Aspartate transcarbamoylase

Aspartate transcarbamoylase ATCase aspartate  carbamoyltransferase,  a key enzyme in pyrimidine  biosynthesis gives a good instance of allosteric  regulation.  The ATCase catalyzes the formation of N-carbamoylaspartate from aspartate and carbamoyl phosphate and is the committed step in pyrimidines biosynthesis in the figure.  Binding  of  the  two  substrates  carbamoyl and aspartate phosphate  is cooperative,  as  described  through  the  sigmoidal  curve  of  V0 against substrate concentration. ATCase consists of six catalytic subunits and six regulatory subunits.  The enzyme  is  feedback-inhibited through  the  end-product  of  the  pathway, CTP which is also known as cytosine triphosphate that acts as an allosteric  inhibitor. This  molecule  connects  to  the  regulatory  subunits  and  causes  a decrease  in  the catalytic  activity  of ATCase  through decreasing  the affinity  of the catalytic  subunits for substrate molecules.  In compare, ATP, one of the intermediates earlier on in the pathway which acts as an allosteric activator enhancing the affinity of ATCase for its substrates and leading to an increase in activity describe in the figure. ATP competes with the similar binding site on the regulatory subunit as CTP.  High  stages  of ATP signal to the cell in which energy is available for DNA replication and so ATCase is activated resulting  in  the  synthesis  of  the  needed  pyrimidine  nucleotides. Whenever pyrimidines are abundant the high levels of CTP inhibit ATCase avoiding needless synthesis of N-carbamoylaspartate and subsequent intermediates in the pathway

Figure: Formation of N-carbamoylaspartate by aspartate transcarbamoylase (ATCase) is the committed step in pyrimidine biosynthesis and a key control point.