Abstract
The enzymes of both de novo and salvage pathways for purine nucleotide synthesis are regulated to meet the demand of nucleic acid precursors during proliferation. Among them, the salvage pathway enzymes seem to play the key role in replenishing the purine pool in dividing and tumour cells that require a greater amount of nucleotides. An imbalance in the purine pools is fundamental not only for preventing cell proliferation, but also, in many cases, to promote apoptosis. It is known that tumour cells harbour several mutations that might lead to defective apoptosis-inducing pathways, and this is probably at the basis of the initial expansion of the population of neoplastic cells. Therefore, knowledge of the molecular mechanisms that lead to apoptosis of tumoural cells is key to predicting the possible success of a drug treatment and planning more effective and focused therapies. In this review, we describe how the modulation of enzymes involved in purine metabolism in tumour cells may affect the apoptotic programme. The enzymes discussed are: ectosolic and cytosolic 5′-nucleotidases, purine nucleoside phosphorylase, adenosine deaminase, hypoxanthine-guanine phosphoribosyltransferase, and inosine-5′-monophosphate dehydrogenase, as well as recently described enzymes particularly expressed in tumour cells, such as deoxynucleoside triphosphate triphosphohydrolase and 7,8-dihydro-8-oxoguanine triphosphatase.
Highlights
Intracellular purine nucleotide concentration is determined and maintained through two distinct pathways, both depending on a common metabolite: 5-phosphoribosyl-1-pyrophosphate (PRPP)(Figure 1)
We describe how the modulation of enzymes involved in purine metabolism in tumour cells may affect the apoptotic programme
As stated before, many effects exerted by the expression of CD73 on tumours are mediated by the participation of the enzyme activity in the conversion of extracellular ATP into Ado, such effects are dependent on the amount and nature of the Ado receptors expressed by tumour cells and other cells present in the tumour microenvironment
Summary
Intracellular purine nucleotide concentration is determined and maintained through two distinct pathways, both depending on a common metabolite: 5-phosphoribosyl-1-pyrophosphate (PRPP). The purinosome formation causes a strong increase in the rate of purine synthesis This regulatory mechanism ensures that, during proliferation and in the absence of preformed purine ring to be salvaged, the supply of purine compounds is secured. The availability of preformed purine ring prevents purinosome formation [2] Regulation both at genetic and protein levels ensures the correct amount of nucleotides to sustain replicative and metabolic needs [3]. It is not surprising that alterations of replicative rate and eventually activation of apoptosis are a consequence of dysfunctions of purine metabolism. The possible applications of this knowledge to anti-tumour in the are activation of apoptosis and the implied molecular mechanisms.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
