Schematic diagram of de novo and salvage purine nucleotide synthesis with points of regulation by Akt

Schematic diagram of de novo and salvage purine nucleotide synthesis with points of regulation by Akt. Glucose (Glu) can be converted to ribose 5-phosphate (Rib-5-P) via either the oxidative or non-oxidative pentose phosphate pathway (PPP). Under normal conditions, most ribose 5-phosphate used in purine synthesis comes from the non-oxidative pathway. Ribose 5-phosphate is converted by PRPP synthetase to PRPP (reaction 1), which is converted to phosphoribosylamine (PRA) by PRPP amidotransferase, the first committed step of the de novo pathway (reaction 2). Glycine combines with phosphoribosylamine to produce glycinamide ribonucleotide (GAR), which is combined with formate to produce FGAR (reaction 3); the latter is converted to AICAR in five subsequent steps (shown as a dashed arrow with the first step, reaction 4, inhibited by azaserine). AICAR and formate are converted by the bifunctional enzyme ATIC (reaction 5) to IMP, which can then be converted to either AMP or GMP. The major routes of AMP and GMP catabolism differ. AMP is converted to hypoxanthine (Hx) via adenosine (Ado) and inosine (Ino), and GMP is converted to guanine (Gua); in both cases ribose 1-phosphate (Rib-1-P) is generated. The ribose 1-phosphate can undergo isomerization to ribose 5-phosphate and then be converted to PRPP, and hypoxanthine and guanine can be converted to IMP by hypoxanthine phosphoribosyltransferase (reaction 6). PRPP production from glucose is shown in green, the de novo purine pathway is shown in pink, purine nucleotide catabolism and the purine salvage pathway are shown in yellow, and points of regulation by PI3K/Akt are shown in red. Glu-6-P, glucose 6-phosphate; 10f-THF, 10-formyltetrahydrofolate.

Publication

The Phosphatidylinositol 3-Kinase/Akt Cassette Regulates Purine Nucleotide Synthesis. (2009) Wei Wang, et al. J Biol Chem. 2009 Feb 6;284(6):3521-3528. Figure: F1. All organisms Drosophila melanogaster Homo sapiens

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