INHIBITION OF INOSINIC ACID DEHYDROGENASE BY 6-CHLOROPURINE NUCLEOTIDE

The inactivation of IMP dehydrogenase of sarcoma 180 ascites tumor cells by 6-chloroinosine 5'-phosphate (ClIMP) has been examined. In the absence of substrates the inhibition of enzymatic activity by this purine nucleotide analog is progressive with time and is not reversed by dialysis. IMP, XMP and GMP protect the enzyme from inactivation by ClIMP, while NAD+, NADH and glutathione do not protect. The data are quantitatively consistent with the hypothesis that ClIMP forms a reversible complex with the active site of the enzyme, with an apparent inhibition constant of 2 × 10-4 M (compared to a Km for IMP of 2 × 10-5 M); this reversible EI complex then slowly decays to form an irreversibly inactivated enzyme. © 1969.