Nucleotide pyrophosphorylase, action

From this brief survey, it is seen that there were few features of carbohydrate metabolism in plants that escaped Hassid s touch, and much that we now know about the role of sugar nucleotides in the interconversion of carbohydrates in plants is a direct result of his persistent effort. From the incorporation of labelled precursors into monosaccharides, to the conversion of the monosaccharides into their glycosyl phosphates, to the action of the pyrophosphorylases in the synthesis of glycosyl esters of nucleoside pyrophosphates, to the interconversion of the resulting sugar nucleotides, to the polymerization of the activated monosaccharides to yield disaccharides and the homopolysaccharides, and, finally, to the modification of the polysaccharides by methylation—in summary, to almost every aspect... 

The reverse phenomenon, decreased enzyme synthesis, can also be the mechanism of drug resistance. The antimetabolite pro-drug 6-mercaptopurine (6MP) is activated to its nucleotide by inosine-5 -phosphate pyrophosphorylase. The enzyme is deleted in resistant neoplastic cells. Resistance to 5-fluorouracil similarly develops by deletion of the enzyme converting this pro-drug to its active nucleotide. A mechanism of resistance by which a drug is excluded from its site of action can also be operative. This has been established for tetracycline antibiotics. Here the permeability of the cellular membrane to the drug is altered so that it cannot penetrate and accumulate within the target cell. Similarly, it has been demonstrated with such a membrane modification in MTX-resistant leukemia cells in mice. 

In liver, specific pyrophosphorylases catalyse the synthesis of nucleotides from free bases and 5-phos-phoribosyl 1-pyrophosphate alternatively, nucleosides may be formed first from bases and ribose 1-phosphate by the action of a nucleoside phosphoiy-lase (Fig.). Deoxynucleosides can be formed from bases and deoxyribose 1-phosphate by the action of deoxynucleoside phosphorylase. 

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