The blocking of the tetrachloroplatinate (II) inhibition of malate dehydrogenase by sulfur-containing amino acids

Abstract

The inhibition of malate dehydrogenase ( l-malate:NAD oxidoreductase, EC 1.1.1.37) by the tetrachloroplatinate (II) complex, PtCl 4 2−, in the presence of various concentrations of the amino acids d l-methionine and l-cysteine was measured. The relative concentrations of PtCl 4 2− to malate dehydrogenase was 100:1. From the data, the half-life and the relative rate of inhibition in the presence and absence of the amino acids were calculated. Using these values it was possible to calculate a stability constant for each system. The stability constants for the malate dehydrogenase-PtCl 4 2−- l-cysteine ( K c ), malate dehydrogenase-PtCl 4 2−- d l-methionine ( K m ) and, malate dehydrogenase-PtCl 4 2−( K E ) were 56 M −1, 917 M −1 and 8·10 5 M −1, respectively. The reversibility of the malate dehydrogenase-PtCl 4 2− complex was also demonstrated, by addition of d l-methionine to the completely inhibited enzyme. About 40% of the enzyme activity was regenerated. Using the stability constants it was calculated that 27% of the enzyme's activity should be regenerated. From the results it is suggested that the free platinum complexes may be maintained in solution for a longer period of time if some or all of the halide ligands were replaced by sulfur groups from molecules like cysteine or methionine.