Pathways for alpha-D-ribose utilization for nucleobase salvage and 5-fluorouracil activation in rat brain.
Recently, interest has increased in the use of alpha-D-ribose (Rib) as a naturally occurring nutriceutical for enhancement of cardiac and muscular performance. Most likely the elevation of available PRPP, following Rib administration, plays a key role in the salvage of purine nucleobases, thus, accelerating the restitution of ATP pool. In addition, administration of Rib improves some of the neurological symptoms in patients with adenylosuccinase deficiency. In this paper, we show that rat brain extract can catalyze the Rib-mediated salvage of both adenine and uracil, as well as the activation of the pyrimidine pro-drug, 5-fluorouracil (5-FU). The results strongly support that the pentose may be converted to both PRPP and Rib1-P for the salvage of the adenine and uracil, respectively. Most likely two-reaction pathway, composed of ribokinase and PRPP synthetase, is responsible of the PRPP formation, needed to salvage adenine to adenine nucleotides. A two-reaction pathway, composed of ribokinase and phosphopentomutase, appears to be responsible of the Rib1-P formation, needed to salvage uracil to uracil-nucleotides and to activate 5-FU to cytotoxic 5-FU-ribonucleotides. alpha-D-2'-Deoxyribose (deoxyRib) has a negligible effect on both the salvage of natural nucleobases to deoxyribonucleotides and on the activation of 5-FU to cytotoxic 5-FU-deoxynucleotides.
Barsotti
Catia
C
Laboratory of Biochemistry, Department of Physiology and Biochemistry, University of Pisa, Via S. Maria 55, 56126, Pisa, Italy.
Ipata
Piero Luigi
PL
D000225:Adenine / Q000378:metabolism; D000818:Animals; D000963:Antimetabolites / Q000378:metabolism*; D001921:Brain; D005472:Fluorouracil / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D010754:Phosphoribosyl Pyrophosphate / Q000378:metabolism; D011685:Purine Nucleotides / Q000378:metabolism; D011742:Pyrimidine Nucleotides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012266:Ribose / Q000378:metabolism*; D014498:Uracil / Q000378:metabolism
D000963:Antimetabolites; D011685:Purine Nucleotides; D011742:Pyrimidine Nucleotides; D014498:Uracil; D012266:Ribose; D010754:Phosphoribosyl Pyrophosphate; D000225:Adenine; D005472:Fluorouracil