Studies on the Mechanism of Purine Nucleotide Inhibition of a Triphosphopyridine Nucleotide-specific Isocitrate Dehydrogenase

A triphosphopyridine nucleotide-specific isocitrate dehydrogenase from Salmonella typhimurium has been shown to be inhibited by purine nucleoside di- and triphosphates. Other nucleotides do not have the same capacity to inhibit the reaction, and the presence of both a purine nucleus and a pyrophosphate moiety seems to be necessary. The nucleotides appear to have a dual action. At low concentration they are competitive inhibitors of TPN+, and at higher concentration they are primarily competitive inhibitors of isocitrate. Evaluation of kinetic data indicates a distinct difference in mechanism of inhibition between ATP and sodium pyrophosphate with respect to the coenzyme. Competition with TPN+ appears to be a function of the purine nucleus, while that with isocitrate probably is due to chelation of Mn++ by the pyrophosphate grouping of the nucleotide.