Multifunctional protein CAD

Oligomeric structure of the multifunctional protein CAD that initiates pyrimidine biosynthesis in mammalian cells. Proc. Natl. Acad. Sci. USA 82, 6802-6806. 

Lee, L., Kelly, R. E., Pastra-Landis, S. C., and Evans, D. R. (1985) Oligomeric structure of the multifunctional protein CAD that initiates pyrimidine biosynthesis in mammalian cells. Proc. Natl. Acad. Sci. U.S.A. 82, 6802—6806. 

Analysis of Intradomain Signaling in the Multifunctional Protein CAD Using Novel Hybrids and Chimeric Molecules... 

There are two multifunctional proteins in the pathway for de novo biosynthesis of pyrimidine nucleotides. A trifunctional protein, called dihydroorotate synthetase (or CAD, where the letters are the initials of the three enzymatic activities), catalyzes reactions 1, 2 and 3 of the pathway (HCC>5"- CAP— CA-asp—> DHO Fig. 15-15). The enzymatic activities of carbamoyl phosphate synthetase, aspartate transcarbamoylase and dihydroorotase, are contained in discrete globular domains of a single polypeptide chain of 243 kDa, where they are covalently connected by segments of polypeptide chain whch are susceptible to digestion by proteases such as trypsin. A bifunctional enzyme, UMP synthase, catalyzes reactions 5 and 6 of the pyrimidine pathway (orotate— OMP—> UMP Fig. 15-15). Two enzymatic activities, those of orotate phosphoribosyltransferase and OMP decarboxylase, are contained in a single protein of 51.5 kDa which associates as a dimer. 

CAD A multifunctional protein that initiates and regulates de novo pyrimidine... 

CAD catalyzes the initial steps (Figure 1) of the de novo pyrimidine biosynthetic pathway in mammalian cells, in which glutamine, ATP, bicarbonate and aspartate are converted to dihydroorotate (i). Dihydroorotate is subsequently oxidized by mitochondrial dihydroorotate dehydrogenase and then converted in two steps to UMP by a second multifunctional protein that has PRPP ttansferase and decarboxylase activities. 

In eukaryotes, enzymes 1 -3 of Figure 22.10 are all part of a single multifunctional polypeptide chain called CAD. In mammals, reactions 5 and 6 are catalyzed by a single protein called UMP synthase. 

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