ODCase have passed through lateral gene transfer, resulting in eukaryotes' having enzymes from bacterial and eukaryotic origin. For instance, Metazoa, Amoebozoa, Plantae, and Heterolobosea have eukaryotic ODCase and OPRTase, whereas Alveolata and stramenopiles have bacterial ones. Other rearrangements are also possible, since Fungi have bacterial OPRTase and eukaryotic ODCase, whereas kinetoplastids have the inverse combination. Merging both the fusion order and evolutionary origin, organisms end up having fused UMPS where one of its catalytic domains comes from bacteria and the other from eukaryotes. The driving force for these fusion events seems to be the acquired thermal stability. Homo sapiens OPRTase and ODCase activities lower to a greater extent when heated than the fused protein does. To determine the driving force of protein association, several experiments have been performed separating both domains and changing the linker peptide that keeps them together. In Plasmodium falciparum, the OPRTase-OMPDCase complex increases the kinetic and thermal stability when compared to monofunctional enzymes. In H. sapiens, even though separate and fused domains have a similar activity, the former have a higher sensitivity to conditions promoting monomer dissociation. Also, the linker peptide can be removed without inactivating catalysis. In Leishmania donovani, separate OPRTase does not have detectable activity possibly due to lower thermal stability or lack of its linker peptide. Regulation UMPS is subject to complex regulation by OMP, the product of its OPRTase and the substrate for the ODCase. OMP is an allosteric activator of OMP decarboxylase activity. At low enzyme concentration and low OMP concentrations, OMP decarboxylase shows negative cooperativity, whereas, at higher OMP concentrations, the enzyme shows positive cooperativity. However, when enzyme concentrations are higher, these complex kinetics do not manifest. Orotate PRTase activity is activated by low concentrations of OMP, phosphate, and ADP. Mechanism OPRTase P. falciparum OPRTase follows a random pathway in OMP synthesis and degradation. Transition state analyses have used isotopic effects and quantum calculations to reveal a completely dissociated dianionic orotate structure, a ribocation, and a nucleophilic pyrophosphate molecule. Nonetheless, this is unexpected, since most N-ribosyltransferases involve protonated and neutral leaving groups, whereas deprotonated orotate is not a good one in the cationic transition state. OPRTase, as a member of type I PRTases, has a prominent loop next to its active site. It is flexible in its open state and can hardly be seen in electronic density maps for some OPRTases. For catalysis to occur, a dimer must exist in