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Lethal synthesis, or suicide metabolism,[1] is the biosynthesis of a toxin from a precursor which is not itself toxic, such as the synthesis of fluorocitrate from fluoroacetate or the synthesis of methylglyoxal from glycerol.[2][3][4]
The term was first publicised by Rudolph Peters in his Croonian Lecture of 1951.[5][3][6]
A 1971 study published by the Harvard Medical School identified methylglyoxal, a form of glycerol, as a product of lethal synthesis in a specific E.coli mutant.[4] In E.coli, the synthesis of triose phosphate from glycerol is a reaction regulated by the synthesis rate of glycerol kinase and by feedback inhibition by fructose-1,6-bisphosphate.[4] The study demonstrated that, in E.coli mutants that had lost both control mechanisms, glycerol kinase no longer reacted to feedback regulation and instead produced the cytotoxic methylglyoxal.[4] A more recent review of research done on methylglyoxal metabolism concluded that the compound's cytotoxic nature is dependent on its ability to form advanced glycation end products (AGEs).[7] These compounds, which are thought to be factors in ageing and in the progression of degenerative diseases, have been shown to hinder the functions of the proteins they target.[7]
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