Methylglyoxal production and detoxification pathways.

(A) MG is formed mainly as a byproduct of glycolysis. In most organisms it is transformed from dihydroxyacetone phosphate (DHAP) by methylglyoxal synthase (MGS). (B) MG production can also result from the metabolism of lipids and proteins. (C) MG detoxification occurs mainly through the glyoxalase system that consists of two enzymes glyoxalase A (GloA) and glyoxalase B (GloB). MG can react non-enzymatically with reduced glutathione (GSH) to form a hemithioacetal which is transformed to S-lactoylglutathione by GloA. S-lactoylglutathione activates potassium efflux pumps that acidify the cytoplasm and confer protection against MG. GloB then transforms S-lactoylglutathione to D-lactate, recycling GSH in the process. Adapted from Allaman et al, 2015 [7].