The Pyruvate-Glyoxalate Pathway as an Alternative Toxicity Assessment Tool of Xenobiotics: Lessons from Prebiotic Chemistry

There is an urgent need to evaluate the toxicity of xenobiotics and complex mixtures the prevention the degradation of water quality sustaining aquatic ecosystems. A simple biogenic chemical pathway based on malate formation from pyruvate (pyr) and glyoxalate (glyox) pathway is proposed as quick and cheap screening tool for toxicity assessment. The assay is based on pyr and glyox (aldol) pathway leading to biologically relevant precursors such as oxaloacetate and malate. Incubation of pyr and glyox at 40-70oC in the presence of reduced iron (FeII) led to formation of malate following the first 3 h of incubation. The addition of various xenobiotics/contaminants (silver, copper, zinc, cerium IV, samarium III, dibytlphthalate, 1,3-diphenylguanidine, carbon-walled nanotube, nanoFe2O3 and polystyrene nanoparticles) led to inhibitions in malate at various degrees. Based on the concentration inhibiting malate concentrations by 20% (IC20), the following potencies were observed: silver < copper ~1.3-diphenylguanidine ~ carbon walled nanotube < zinc ~ samarium < dibutylphthalate ~ samarium < Ce(IV) < nFeO3< polystyrene nanoplastics. The IC20 values were also significantly correlated with the reported trout acute lethality data making this test a potential alternative test for trout. The per-glyox was also tested on surface water extracts (C18) and identified the most contaminated sites from large cities and municipal wastewater effluents. The inhibition potencies of the selected test compounds revealed that not only pro-oxidants are associated to toxicity but chemicals hindering enolate formation, nucleophilic attack of carbonyls and dehydration involved in aldol condensation reactions were also associated to toxicity. The per-glyox pathway is based on a fundamental aspect of chemical reactions during the emergence of life and represents a unique tool to identify toxic compounds individually and in complex mixtures.