Inhibition of Human Erythrocyte Glucose 6-Phosphate Dehydrogenase by Cadmium,Nickel and Aluminium

The inhibition of human erythrocyte glucose 6-phosphate dehydrogenase (G6PD) by Cd (II), Al (III) and Ni (II) was studied. The enzyme was partially purified having specific activity of 1.4 U/mg protein. Cadmium inhibited G6PD activity progressively up to 1.5 mM concentration where about 65% of the enzyme activity was lost. The inhibition was uncompetitive and noncompetitive with respect to glucose 6-phosphate and NADP+, respectively. Cd (II) also increased maximum emission spectrum of the intrinsic protein fluorescence. Sulfhydryl compounds such as glutathione (1.2 mM), β-mercaptoethanol (1.2 mM) or dithiothreitol (1.25 mM) protected the enzyme activity against Cd (II) inhibition and restored the native protein fluorescence. The data suggest that sulfhydryl groups are involved in Cd (II) inhibition. The inhibition patterns for Al (III) were mixed type and competitive when NADP+ and glucose 6-phosphate were the variable substrates, respectively. The enzyme inhibition by Al (III) was increased as the pH of the incubation mixture decreased indicating that mainly the ionized form of Al (III) abolishes the enzyme activity. The types of the enzyme inhibition by Ni (II) were competitive with respect to NADP+ and mixed type when glucose 6-phosphate varied. Ki values of 1.5 mM, 0.039 mM 0.05 mM for Cd (II), Al (III) and Ni (II) were calculated from the slope replots, respectively. The data suggest that direct interaction of these metal ions with human erythrocyte G6PD produces a reversible inhibition of the enzyme and that their toxicity, at least in part, may be due to the inhibition of this enzyme.