Deoxyribose 1-phosphate phosphorolysis

As already stated, cells would appear to have the means of converting bases into deoxyribonucleotides through the reversibility of nucleoside phosphorolysis, providing deoxyribose 1-phosphate was available. It will be seen below that the coupled activities of deoxyriboaldolase and phos-phoribomutase (enzymes involved in degradation of deoxyribose phosphates) will generate deoxyribose 1-phosphate in vitro under certain conditions and, therefore, these enzymes represent a possible cellular source of this compound. However, it has not been demonstrated that any contribution to the formation of deoxyribonudeoside phosphates is made by... 

A close look at this reaction reveals that in the opposite direction, the reaction is of the phosphorolysis type. For this reason, the enzymes catalyzing the reaction with ribose-l-phosphate are called phosphorylases, and they also participate in nucleic acid degradation pathways. Purine nucleoside phosphorylases thus convert hypoxanthine and guanine to either inosine and guanosine if ribose-l-phosphate is the substrate or to deoxyinosine and deoxyguanosine if deoxyribose-1-phosphate is the substrate. Uridine phosphorylase converts uracil to uridine in the presence of ribose-l-phosphate, and thymidine is formed from thymine and deoxyribose-l-phosphate through the action of thymidine phosphorylase. 

Purine nucleosides are cleaved by the action of purine nucleoside phosphorylase with the liberation of ribose 1-phosphate (Kl, PI). The enzyme is apparently specific for purines. The material from erythrocytes catalyzes the phosphorolysis of purine but not pyrimidine nucleosides (T6.) Purine phosphorylase activity is found widespread in nature and in many animal tissues (FIO). Friedkin and Kalckar investigated an enzyme capable of cleaving purine deoxynucleosides to the aglycone and deoxy-ribose 1-phosphate. They concluded that the enzyme was identical to that which splits purine ribonucleosides (F8, F9). This enzyme is capable of degrading inosine, xanthosine, and guanosine to forms readily attacked by other enzymes. In so doing, it permits living cells to retain the ribose and deoxyribose moieties. 

Purine nucleoside phosphorylase (PNP) catalyses the phosphorolysis of purine ribonucleosides and 2 -deoxyribo-nucleosides to the purine base and ribose- or 2-deoxyribose-a-1-phosphate. PNP is a key enzyme in the T-cell-mediated immune response. As such, it is an attractive target in a number of therapeutic areas, such as organ transplantation, T-cell-mediated autoimmune disorders and T-cell proliferative diseases. PNP has been the subject of a thorough and successful structure-based drug design study, of which the following gives only a flavour. 

Deoxyribose 1-phosphate, derived from initial phosphorolysis of deoxyribonucleoside BidR, is utilized to form the new nucleoside B2dR, the net result (3) being deoxyribosyl transfer. This sequence is phosphate-de-pendent. 

---