De novo biosynthesis of pyrimidine ribonucleotides (WP92)

Purine and pyrimidine nucleotides have many diverse and essential roles in the cell. They are precursors to DNA, RNA, and many important metabolites (for example CDP-diacylglycerol). Nucleotides can also be used as an energy source (primarily as ATP), signaling molecules, and cofactor components (for example coenzyme A). In yeast, the initial steps of de novo pyrimidine biosynthesis are catalyzed by the bifunctional carbamoylphosphate synthetase/aspartate transcarbamylase Ura2p. In the first step, Ura2p catalyzes the synthesis of carbamoylphosphate from CO2, ATP, and glutamine. In the second, Ura2p condenses carbamoylphosphate with aspartate to yield ureidosuccinate/carbamoyl-L-aspartate. Third, dihydroorotase (Ura4p) catalyzes closure of the pyrimidine ring of ureidosuccinate to form dihydroorotate (DHO). DHO, in turn, is oxidized to orotic acid (OA), condensed with phosphoribosyl pyrophosphate to form orotidine 5-monophosphate, and finally decarboxylated to yield UMP. These three steps are catalyzed by Ura1p, Ura5p/Ura10p, and Ura3p, respectively. UMP may then undergo further processing to form other pyrimidines. Source: https://pathway.yeastgenome.org/

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