Effect of Fe2+ and Mn2+ on 3-mercaptopicolinate inhibition of cytosolic and mitochondrial phosphoenolpyruvate carboxykinase of five species.

Liver cytosolic or mitochondrial fractions of five species were incubated with 30 micrometer Fe2+ or with 100 micrometer Mn2+ prior to assaying for phosphoenolpyruvate carboxykinase (GTP:oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32) acticity in the presence of 3-mercaptopicolinate. Only the cytosolic carboxykinases were activated 3--4-fold by Fe2+ or Mn2+. Fe2+ enhanced the inhibitory potency of 3-mercaptopicolinate 10--50-fold against the cytosolic and the mitochondrial carboxykinases, but Mn2+ was ineffective. Mn2+ interfered with Fe2+ -enhancement of inhibition by 3-mercaptopicolinate in a manner competitive with Fe2+. It is hypothesized that Fe2+ and 3-mercaptopicolinate form a coordination complex that inhibits the carboxylkinases and that 3-mercaptopicolinate does not blind to a carboxykinase containing Mn2+.