Figure 1

Organization and allosteric regulatory properties of the enzymes catalyzing the first three reactions of the pyrimidine pathway in E. coli , S. cerevisiae and mammals. This scheme shows the functional domains that catalyze the first steps in the de novo pyrimidine biosynthetic pathway, the amidotransferase or glutaminase domain (GLNase), the CPSase synthetase domain consisting of two subdomains (CPS-A and CPS-B), the dihydroorotase domain (DHOase), and the ATCase domain. The activities are associated with separate polypeptide chains in E. coli, whereas in mammals (CAD) all are consolidated on a single multifunctional protein. In yeast, the CPSase and ATCase domains are carried by a single polypeptide, but in this case the active DHOase that is encoded by a separate gene is replaced with an inactive DHOase homologue (pDHO). Eucaryotes ATCases lack the regulatory subunit (Reg) found in the E. coli protein. The scheme also shows the allosteric effectors that regulate the activity of these proteins and the localization of the regulatory sites represented by arrows.