The effect of zinc on the oxidation of krebs cycle intermediates by rat liver and kidney homogenates

Zinc ions in small concentrations (2 × 10^?5M) inhibit rat liver and kidney succinoxidase systems by forming an inactive complex with the enzyme. Under conditions which favor oxidative phosphorylation (isotonic KCl homogenates, Mg ion, and muscle adenylate or adenosine triphosphate), inhibition by zinc occurs, but this inhibition is transitory. The rate of oxidation subsequently rises to a level even higher than shown by the control data. A later fall to a lower level of activity can be attributed to the zinc inhibition of other Krebs cycle intermediates, particularly the oxidation of α-ketoglutarate and citrate. The addition of a protein such as insulin has no protective action against zinc inhibition, and crystalline zinc insulin causes the same inhibition as does zinc sulfate. With the exception of succinoxidase, the oxidizing enzymes of rat kidney are more readily inhibited by zinc ions than are those of rat liver.Amorphous insulin, in itself, inhibits citrate oxidation by rat kidney homogenates.