Regulation of purine biosynthesis in cultured human cells

Add time:08/09/2019    Source:sciencedirect.com

Orotic acid, an intermediate in the synthesis of pyrimidine nucleotides, has been shown in the present study to inhibit an early step of purine biosynthesis de novo in cultured human cells as manifested by the decreased synthesis of N-formylglycinamide ribonucleotide (FGAR). Concentrations of orotic acid that inhibited purine synthesis also reduced intracellular levels of 5-phosphoribosyl 1-pyrophosphate (PP-ribose-P), an essential substrate for the first enzyme unique to this pathway. Orotic acid had no inhibitory effect on FGAR synthesis in mutant cells with high PP-ribose-P levels or in normal cells if depletion of PP-ribose-P by orotic acid was prevented with azaorotate. These studies provide substantial evidence that the inhibitory effect of orotic acid on purine synthesis in cultured human cells is due to a depletion of intracellular PP-ribose-P.

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