Guanosine 5 -phosphate pyrophosphorylase

Human neoplasm cells in culture show a different type of resistance to 6-mercaptopurine from that cited above, in that they delete the enzyme responsible for converting this pro-drug to the therapeutic nucleotide (6-thioinosine 5 -phosphate) (Brockman, 1963). The deleted enzyme is inosine 5 -phosphate pyrophosphorylase. Similarly, resistance to 8-azaguanine is accompanied by loss of the enzyme guanosine 5 -phosphate pyrophosphorylase in human epidermoid carcinoma cells (Brockman et al., 1961). Resistance to 5-fluoro-uracil also depends on the uneconomic cell s ceasing to convert this pro-drug to the nucleotide. 

This enzyme [EC 2.7.7.28], also known as NDP-hexose pyrophosphorylase, catalyzes the reaction of a nucleoside triphosphate with a hexose 1-phosphate to produce a NDP-hexose and pyrophosphate (or, diphosphate). In the reverse reaction the NDP-hexose can be, in decreasing order of activity, guanosine, inosine, and adenosine diphosphate hexoses in which the sugar is either glucose or mannose. 

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