Abstract.
The de novo biosynthesis of pyrimidine nucleotides provides essential precursors for multiple growth-related events in higher eukaryotes. Assembled from ATP, bicarbonate and glutamine, the uracil and cytosine nucleotides are fuel for the synthesis of RNA, DNA, phospholipids, UDP sugars and glycogen. Over the past 2 decades considerable progress has been made in elucidating the mechanisms by which cellular pyrimidines are modulated to meet the needs of the cell. Recent studies demonstrate that CAD, a rate-limiting enzyme in the de novo synthesis of pyrimidines, is regulated through reversible phosphorylation, Myc-dependent transcriptional changes and caspase-mediated degradation. These studies point to increasing evidence for cooperation between key cell signaling pathways and basic elements of cellular metabolism, and suggest that these events have the potential to determine distinct cellular fates, including growth, differentiation and death. This review highlights some of the recent advances in the regulation of pyrimidine synthesis by growth-factor-stimulated signaling pathways.
Similar content being viewed by others
Author information
Authors and Affiliations
Additional information
Received 12 July 2002; accepted 24 July 2002
RID="*"
ID="*"Corresponding author.
Rights and permissions
About this article
Cite this article
Huang, M., Graves, L. De novo synthesis of pyrimidine nucleotides; emerging interfaces with signal transduction pathways. CMLS, Cell. Mol. Life Sci. 60, 321–336 (2003). https://doi.org/10.1007/s000180300027
Issue Date:
DOI: https://doi.org/10.1007/s000180300027