On demand utilization of phosphoribosyl pyrophosphate by downstream anabolic pathways - Archive ouverte HAL
Article Dans Une Revue Journal of Biological Chemistry Année : 2023

On demand utilization of phosphoribosyl pyrophosphate by downstream anabolic pathways

Résumé

The pentose phosphate pathway (PPP) is critical for anabolism and biomass production. Here we show that the essential function of PPP in yeast is the synthesis of phosphoribosyl pyrophosphate (PRPP) catalyzed by PRPP-synthetase. Using combinations of yeast mutants, we found that a mildly decreased synthesis of PRPP affects biomass production, resulting in reduced cell size, while a more severe decrease ends up affecting yeast doubling time. We establish that it is PRPP itself that is limiting in invalid PRPP-synthetase mutants and that the resulting metabolic and growth defect can be bypassed by proper supplementation of the medium with ribose-containing precursors or by the expression of bacterial or human PRPPsynthetase. In addition, using documented pathologic human hyperactive forms of PRPPsynthetase, we show that intracellular PRPP as well as its derived products can be increased in both human and yeast cells and we describe the ensuing metabolic and physiological consequences. Finally, we found that PRPP consumption appears to take place "on demand" by the various PRPP-utilizing pathways, as shown by blocking or increasing the flux in specific PRPP-consuming metabolic routes. Overall, our work reveals important similarity between human and yeast for both synthesis and consumption of PRPP.
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Dates et versions

hal-04151647 , version 1 (05-07-2023)

Identifiants

Citer

Benoît Pinson, Michel Moenner, Christelle Saint-Marc, Alexandra Granger-Farbos, Bertrand Daignan-Fornier. On demand utilization of phosphoribosyl pyrophosphate by downstream anabolic pathways. Journal of Biological Chemistry, In press, ⟨10.1016/j.jbc.2023.105011⟩. ⟨hal-04151647⟩

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