Pentose phosphates in nucleoside interconversion and catabolism

Abstract

Pentose phosphates are heterocyclic, five-membered, oxygen-containing phosphorylated ring structures, with ribose-5-phosphate (Rib-5-P) and 2-deoxyribose-5-phosphate (deoxyRib-5-P) being basal structures of ribonucleotides and deoxyribonucleotides, respectively, and 5-phosphoribosyl-1-pyrophosphate (PRPP) the common precursor of both de novo and 'salvage' synthesis of nucleotides. Two main pathways are involved in pentose phosphate biosynthesis (Fig. 1). In the oxidative branch of the pentose phosphate pathway, Rib-5-P is generated from glucose-6-phosphate. In the phosphorylase-mediated pathway, deoxyribose-1- Ribose phosphates are either synthesized through the oxidative branch of the pentose phosphate pathway, or are supplied by nucleoside phosphorylases. The two main pentose phosphates, ribose-5-phosphate and ribose-1-phosphate, are readily interconverted by the action of phosphopentomutase. Ribose-5-phosphate is the direct precursor of 5-phosphoribosyl-1-pyrophosphate, for both de novo and 'salvage' synthesis of nucleotides. Phosphorolysis of deoxyribonucleosides is the main source of deoxyribose phosphates, which are interconvertible, through the action of phosphopentomutase.The pentose moiety of all nucleosides can serve as a carbon and energy source. During the past decade, extensive advances have been made in elucidating the pathways by which the pentose phosphates, arising from nucleoside phosphorolysis, are either recycled, without opening of their furanosidic ring, or catabolized as a carbon and energy source. We review herein the experimental knowledge on the molecular mechanisms by which (a) ribose-1-phosphate, produced by purine nucleoside phosphorylase acting catabolically, is either anabolized for pyrimidine salvage and 5-fluorouracil activation, with uridine phosphorylase acting anabolically, or recycled for nucleoside and base interconversion; (b) the nucleosides can be regarded, both in bacteria and in eukaryotic cells, as carriers of sugars, that are made available though the action of nucleoside phosphorylases. In bacteria, catabolism of nucleosides, when suitable carbon and energy sources are not available, is accomplished by a battery of nucleoside transporters and of inducible catabolic enzymes for purine and pyrimidine nucleosides and for pentose phosphates. In eukaryotic cells, the modulation of pentose phosphate production by nucleoside catabolism seems to be affected by developmental and physiological factors on enzyme levels.Abbreviations

The Pentose Moiety of Adenosine and Inosine Is an Important Energy Source for the Fermented-Meat Starter Culture Lactobacillus sakei CTC 494

“…This indicates that adenosine is not first converted into inosine, as has been proposed before (2). A complete recovery of hypoxanthine in the medium also occurs in the case of Bacillus cereus NCIB 8122 when grown on inosine as the sole energy source (15,40). This was also the case for L. lactis and B. subtilis strains, which do not grow on inosine and adenosine as the sole energy sources (16,34).…”

“…No adenosine deaminase activity occurred, as was predicted by the genome-scale model of L. sakei 23K (2) and as experimentally shown for Bacillus spp. and Escherichia coli (14,15,40). When glucose was added to the growth medium in combination with adenosine or inosine, the catabolism of these nucleosides started after all glucose was depleted, suggesting carbon catabolite repression as a regulatory mechanism involved in nucleoside catabolism by L. sakei.…”

“…This has been shown for Bacillus spp. and E. coli strains as well (40), underlining that ribonucleosides are carriers of ribose as fermentable carbohydrates for all of these bacterial species when free carbohydrates are lacking.…”

Accumulation of thymidine-derived sugars in thymidine phosphorylase overexpressing cells

“…dR-1-P can also be formed by conversion of purine deoxynucleosides by purine nucleoside phosphorylase (PNP) [32]. Therefore theoretically, PNP may also be an angiogenic enzyme.…”

Paracrine Stimulation of Endothelial Cell Motility and Angiogenesis by Platelet-Derived Deoxyribose-1-Phosphate

“…14 -16 dRP is the product of the phosphorolytic degradation of deoxynucleosides in the "nucleotide salvage pathway," which is catalyzed by 3 enzymes in mammalian cells: thymidine phosphorylase (TP, or platelet-derived endothelial cell growth factor, EC 2.4.2.4), uridine phosphorylase (UP, EC 2.4.2.3), and purine nucleoside phosphorylase (PNP, EC 2.4.2.1). 17 We have used pharmacological inhibitors of TP, UP, or PNP in human platelets and the genetic ablation of TP and UP in mouse platelets to investigate whether platelet-derived dRP stimu- …”