Mode of Action of 5 : 6-Dimethylbenzimidazole and Certain Keto-Acids as Inhibitors of Hæm Biosynthesis

Abstract

Abbott and Dodson¹ reported an inhibition by 5 : 6-dimethylbenzimidazole of the incorporation of ¹⁵N-glycine into hæm by chicken erythrocyte preparations. Later work by Abbott, Dodson and Auvil² showed that this inhibition is at a step prior to the formation of δ-aminolævulic acid in the biosynthetic pathway. Recently, it has been reported³ that the inhibition is to be located in those steps of δ-aminolævulic acid synthesis which involve either activation of glycine, in which pyridoxal phosphate is concerned, or condensation of the activated glycine derivative with succinyl-coenzyme A. Production of succinyl-coenzyme A itself is not inhibited by 5 : 6-dimethylbenzimidazole in the chicken erythrocyte preparations used³. Evidence has been presented recently⁴ for the involvement of ferrous iron in the biosynthesis of δ-aminolævulic acid ; work described at the same time showed that ferrous iron consistently diminished the inhibition by 5 : 6-dimethylbenzimidazole of δ-aminolævulic acid biosynthesis. Several other metal ions examined, including ferric iron, did not have this effect.