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

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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.

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References

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Authors and Affiliations

  1. Department of Chemical Pathology, University College Hospital Medical School, London, W.C.1.

    E. G. BROWN

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  1. E. G. BROWN
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BROWN, E. Mode of Action of 5 : 6-Dimethylbenzimidazole and Certain Keto-Acids as Inhibitors of Hæm Biosynthesis. Nature 182, 1091–1092 (1958). https://doi.org/10.1038/1821091a0

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