EFFECT OF ORGANIC FORMS OF SELENIUM ON DELTA-AMINOLEVULINATE DEHYDRATASE FROM LIVER, KIDNEY, AND BRAIN OF ADULT RATS

The inhibitory effect of various forms of organic selenium compounds a nd of diphenyl ditelluride (PhTe)(2) on delta-aminolevulinate dehydrat ase (delta-ALA-D) from liver, kidney, and brain of rats was investigat ed because it has been reported that organocalcogens catalyze the oxid ation of thiols. Diphenyl diselenide (PhSe)(2), p-chloro-diphenyl dise lenide (pClPhSe)(2), propyl-2-2-diphenyl diselenide, and propyl-2-meth oxy-2-phenyl selenide inhibited delta-ALA-D and the IC50 ranged from 2 to 32 mu M depending on the selenium compound and whether it was prei ncubated with the enzyme. (pClPhSe)(2) was the most potent inhibitor o f delta-ALA-D, and preincubation increased the inhibitory potency of a ll the tested compounds. Inorganic selenium compounds (sodium selenite , Na2SeO3 and selenium dioxide, SeO2) inhibited delta-ALA-D, and the p otency of SeO, was greater than that of(pC1PhSe)(2). Diphenyl ditellur ide (PhTe)(2) also inhibited delta-ALA-D but with relatively lower pot ency than that of organic and inorganic selenium compounds. The inhibi tory effect of propyl-2-2-diphenyl diselenide and propyl-2-methoxy-2-p henyl selenide seems to be mediated by (PhSe)(2) since the compounds d ecomposed rapidly to (PhSe)(2) in aqueous medium. The inhibitory actio n of selenium forms on delta-ALA-D from liver, kidney, and brain was a ntagonized by sulfhydryl protecting agents (dithiotreitol and reduced glutathione). The effects of organic seleniun compounds on delta-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 (Ph Se)(2) was not related to the formation of oxyradicals in the medium s ince superoxide dismutase and catalase did not affect the inhibition o f delta-ALA-D by (PhSe)(2). delta-ALA-D from cucumber leaves was not i nhibited by selenium or tellurium compounds, which suggests that these compounds act directly on the B or beta-site of the animal enzyme. Th ese results suggest that delta-ALA-D from liver, kidney, and brain is a potential molecular target for the toxic effect of organic forms of selenium and tellurium. (C) 1998 Academic Press.