Purine ribonucleotide interconversion pathways

The reactions of purine ribonucleotide interconversion may be arranged in two cycles which have inosinate as the common intermediate. One may ask exactly what is the function of these two cycles, into which there are so many points of entry the question may also be asked whether these pathways actually function in a cyclic manner. 

As a redox couple, proline and pyrroline-5-carboxylate provide a mechanism for the intercompartmental and intercellular transfer of redox potential. The transfer of redox potential alters the ratio of NADP /NADPH thereby activating certain metabolic pathways. Although the reduction of pyrroline-5-carboxylate is the central mechanism in the transfer of redox potential, the metabolic interconversions of proline, ornithine, and glutamate with pyrroline-5-carboxylate as the obligate intermediate also may play a role. The endpoint of this regulation appears to be the formation of purine ribonucleotides by both salvage and de novo mechanisms. Proline and pyrroline-5-carboxylate appear to be metabolic signals which can be fine-tuned by humoral factors to coordinate the metabolism of amino acids and ribonucleotides. When the transfer is from cell to cell, proline and pyrroline-5-carboxyl-ate can function as intercellular communicators. 

Biosynthesis and function of RNA - Mcmy inhibitors of RNA synthesis, such as aotinomycin, act by complexing with DNA and inhibiting its template function in the biosynthesis of RNA.3 Base analogs, such as 6-mercapto-purine and 8-azaguanine, interfere with interconversions of ribonucleotide subunits and inhibit novo synthesis of RNA.3 Utilization of these biochemical pathways for the design of chemotherapeutic agents is limited by considerations similar to those discussed for inhibitors of DNA synthesis. 

Fig. 23.1. Pyrimidine pathways Pathways for the de novo synthesis, interconversion, and breakdown of pyrimidine ribonucleotides, indicating their metabolic importance as the essential precursors of the pyrimidine sugars and, with purines, of DNA and RNA. Note that in contrast to purines salvage takes place at the nucleoside not the base level in human cells and pyrimidine metabolism normally lacks any detectable end-product. The importance of this network is highlighted by the variety of clinical symptoms associated with the possible enzyme defects indicated. 23.10, Uridine monophosphate synthase (UMPS), 23.11a, uridine monophosphate hydrolase 1 (UMPHl), 23.12, thymidine phosphorylase (TP), 23.13, dihydropyrimidine dehydrogenase (DPD), 23.14, dihydropyrimidine amidohydrolase (DHP), 23.15, y -ureidopropionase (UP) (23.11b, UMPH superactivity specific to fibroblasts is not shown). CP, carbamoyl phosphate. The pathological metabolites used as specific markers in differential diagnosis are highlighted...

---