INHIBITION OF INOSINIC ACID DEHYDROGENASE OF SARCOMA 180 ASCITES CELLS BY NUCLEOTIDES AND THEIR ANALOGS

IMP dehydrogenase of sarcoma 180 ascites tumor cells is inhibited in a competitive manner by the guanine nucleotide biosynthetic pathway end-product GMP. The effectiveness of IMP as a substrate and of GMP as an inhibitor was mimicked less strongly by dIMP and dGMP, as well as by the corresponding nucleoside di- and triphosphate compounds. 8-Azaguanosine 5'-phosphate, 2-amino-6-chloropurine ribonucleoside 5'-phosphate, 2,6-diaminopurine ribonucleoside 5'-phosphate and AMP, which also may be considered to be derivatives of GMP and IMP, produced inhibition of enzymatic activity. IMP, XMP and GMP behaved similarly in protecting IMP dehydrogenase from inhibition by N-ethylmaleimide. No evidence was found requiring the postulation of an allosteric site in the mammalian enzyme for the feedback inhibitor GMP. © 1969.