CAD, A Multienzymatic Protein at the Head of de Novo Pyrimidine Biosynthesis

  • Francisco del Caño-Ochoa
  • María Moreno-Morcillo
  • Santiago Ramón-MaiquesEmail author
Part of the Subcellular Biochemistry book series (SCBI, volume 93)


CAD is a 1.5 MDa particle formed by hexameric association of a 250 kDa protein that carries the enzymatic activities for the first three steps in the de novo biosynthesis of pyrimidine nucleotides: glutamine-dependent Carbamoyl phosphate synthetase, Aspartate transcarbamoylase and Dihydroorotase. This metabolic pathway is essential for cell growth and proliferation and is conserved in all living organisms. However, the fusion of the first three enzymatic activities of the pathway into a single multienzymatic protein only occurs in animals. In prokaryotes, by contrast, these activities are encoded as distinct monofunctional enzymes that function independently or by forming more or less transient complexes. Whereas the structural information about these enzymes in bacteria is abundant, the large size and instability of CAD has only allowed a fragmented characterization of its structure. Here we retrace some of the most significant efforts to decipher the architecture of CAD and to understand its catalytic and regulatory mechanisms.


Glutaminase Carbamoyl phosphate synthetase Aspartate transcarbamoylase Dihydroorotase Nucleotide metabolism PALA Metabolic disease 


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Francisco del Caño-Ochoa
    • 1
  • María Moreno-Morcillo
    • 1
  • Santiago Ramón-Maiques
    • 1
    Email author
  1. 1.Department of Genome Dynamics and FunctionCentro de Biología Molecular Severo Ochoa (CSIC-UAM)MadridSpain

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