Effect of Organic Forms of Selenium on δ-Aminolevulinate Dehydratase from Liver, Kidney, and Brain of Adult Rats

Abstract

The inhibitory effect of various forms of organic selenium compounds and of diphenyl ditelluride (PhTe)2on δ-aminolevulinate dehydratase (δ-ALA-D) from liver, kidney, and brain of rats was investigated because it has been reported that organocalcogens catalyze the oxidation of thiols. Diphenyl diselenide (PhSe)2, ρ-chloro-diphenyl diselenide (ρClPhSe)2, propyl-2-2-diphenyl diselenide, and propyl-2-methoxy-2-phenyl selenide inhibited δ-ALA-D and the IC50 ranged from 2 to 32 μM depending on the selenium compound and whether it was preincubated with the enzyme. (ρClPhSe)2was the most potent inhibitor of δ-ALA-D, and preincubation increased the inhibitory potency of all the tested compounds. Inorganic selenium compounds (sodium selenite, Na2SeO3and selenium dioxide, SeO2) inhibited δ-ALA-D, and the potency of SeO2was greater than that of (ρClPhSe)2. Diphenyl ditelluride (PhTe)2also inhibited δ-ALA-D but with relatively lower potency than that of organic and inorganic selenium compounds. The inhibitory effect of propyl-2-2-diphenyl diselenide and propyl-2-methoxy-2-phenyl selenide seems to be mediated by (PhSe)2since the compounds decomposed rapidly to (PhSe)2in aqueous medium. The inhibitory action of selenium forms on δ-ALA-D from liver, kidney, and brain was antagonized by sulfhydryl protecting agents (dithiotreitol and reduced glutathione). The effects of organic selenium compounds on δ-ALA-D were related to the stability of the Se–Se (or Se–C) bond because the compound methyl-diphenyl diselenide (which possesses the most stable Se–C–Se bond) did not inhibit the enzyme. The inhibitory action of (PhSe)2was not related to the formation of oxyradicals in the medium since superoxide dismutase and catalase did not affect the inhibition of δ-ALA-D by (PhSe)2. δ-ALA-D from cucumber leaves was not inhibited by selenium or tellurium compounds, which suggests that these compounds act directly on the B or β-site of the animal enzyme. These results suggest that δ-ALA-D from liver, kidney, and brain is a potential molecular target for the toxic effect of organic forms of selenium and tellurium.