5-Iodoribose 1-phosphate, an analog of ribose 1-phosphate. Enzymatic synthesis and kinetic studies with enzymes of purine, pyrimidine, and sugar phosphate metabolism.
The 5'-deoxy-5'-iodo-substituted analogs of adenosine and inosine are cytotoxic to tumor cells that have high activities of 5'-methylthioadenosine phosphorylase and purine nucleoside phosphorylase, respectively (Savarese, T.M., Chu, S-H., Chu, M.Y., and Parks, R. E., Jr. (1984) Biochem. Pharmacol. 34, 361-367). 5-Iodoribose 1-phosphate (5-IRib-1-P), the common intracellular metabolite of these 5'-iodonucleosides, has been synthesized enzymatically from 5'-deoxy-5'-iodoadenosine via adenosine deaminase from Aspergillus oryzae and human erythrocytic purine nucleoside phosphorylase. The purification and chemical properties of 5-IRib-1-P are described. The analog sugar phosphate inhibited purine nucleoside phosphorylase from human erythrocytes, phosphoglucomutase from rabbit muscle, and 5'-methylthioadenosine phosphorylase from Sarcoma 180 cells with Ki values of 26, 100, and 9 microM, respectively. Enzymes that react with 5-phosphoribosyl 1-pyrophosphate (P-Rib-PP), P-Rib-PP amidotransferase, hypoxanthine-guanine phosphoribosyltransferase, adenine phosphoribosyltransferase, and orotate phosphoribosyltransferase-orotidylate decarboxylase from extracts of Sarcoma 180 cells, were inhibited with Ki values of 49, 465, 307, and 275 microM, respectively. 5-IRib-1-P had no effect on P-Rib-PP synthetase. Since the Ki values of the analog sugar phosphate for 5'-methylthioadenosine phosphorylase and P-Rib-PP amidotransferase are much lower than the Km values of the natural substrates, Pi or P-Rib-PP which are reported to be present at nonsaturating concentrations under physiological conditions, these enzymes could be significantly inhibited by 5-IRib-1-P in intact cells.
D000243:Adenosine Deaminase / Q000378:metabolism*; D000818:Animals; D001230:Aspergillus / Q000201:enzymology; D004912:Erythrocytes / Q000201:enzymology; D006151:Guanosine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009132:Muscles / Q000201:enzymology; D009700:Nucleoside Deaminases / Q000378:metabolism*; D010428:Pentosephosphates / Q000378:metabolism*; D010430:Pentosyltransferases / Q000378:metabolism*; D010733:Phosphoglucomutase / Q000378:metabolism*; D011683:Purine-Nucleoside Phosphorylase / Q000378:metabolism*; D011817:Rabbits; D012267:Ribosemonophosphates / Q000378:metabolism*; D012510:Sarcoma 180 / Q000201:enzymology
D010428:Pentosephosphates; D012267:Ribosemonophosphates; C047626:5-iodoribose 1-phosphate; D006151:Guanosine; C047627:8-amino-5'-iodoguanosine; C031154:ribose 1-phosphate; D010430:Pentosyltransferases; D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase; D010733:Phosphoglucomutase