Phospholipid biosynthesis modulates nucleotide metabolism and reductive capacity.

Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101231976 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-4469 (Electronic) Linking ISSN: 15524450 NLM ISO Abbreviation: Nat Chem Biol Subsets: MEDLINE

Original Publication: New York, NY : Nature Pub. Group, [2005]-

Saccharomyces cerevisiae*/metabolism ; Saccharomyces cerevisiae*/genetics ; Oxidation-Reduction* ; Phospholipids*/metabolism ; Phospholipids*/biosynthesis ; Nucleotides*/metabolism ; Nucleotides*/biosynthesis; NADP/metabolism ; Pentose Phosphate Pathway ; Cytidine Triphosphate/metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Antioxidants/metabolism ; Glutathione/metabolism ; Glutathione/biosynthesis

Phospholipid and nucleotide syntheses are fundamental metabolic processes in eukaryotic organisms, with their dysregulation implicated in various disease states. Despite their importance, the interplay between these pathways remains poorly understood. Using genetic and metabolic analyses in Saccharomyces cerevisiae, we elucidate how cytidine triphosphate usage in the Kennedy pathway for phospholipid synthesis influences nucleotide metabolism and redox balance. We find that deficiencies in the Kennedy pathway limit nucleotide salvage, prompting compensatory activation of de novo nucleotide synthesis and the pentose phosphate pathway. This metabolic shift enhances the production of antioxidants such as NADPH and glutathione. Moreover, we observe that the Kennedy pathway for phospholipid synthesis is inhibited during replicative aging, indicating its role in antioxidative defense as an adaptive mechanism in aged cells. Our findings highlight the critical role of phospholipid synthesis pathway choice in the integrative regulation of nucleotide metabolism, redox balance and membrane properties for cellular defense.
Competing Interests: Competing interests: The authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

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0 (Phospholipids)
0 (Nucleotides)
53-59-8 (NADP)
65-47-4 (Cytidine Triphosphate)
0 (Saccharomyces cerevisiae Proteins)
0 (Antioxidants)
GAN16C9B8O (Glutathione)

Date Created: 20240726 Date Completed: 20241223 Latest Revision: 20241224

20241225

10.1038/s41589-024-01689-z

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