The role of alpha,beta-dicarbonyl compounds in the toxicity of short chainsugars

The extent to which sugars serve as targets for superoxide was examined usi ng glycolaldehyde as the simplest sugar and using superoxide dismutase (SOD )-replete and SOD-null strains growing under aerobic and anaerobic conditio ns. Glycolaldehyde was more toxic to the SOD-null strain than to its SOD re plete parent, and this differential effect was oxygen-dependent. The produc t, glyoxal, could be trapped in the medium by 1,2-diaminobenzene and assaye d as quinoxaline. The SOD-null strain produced more glyoxal and eliminated it more slowly than the SOD-replete parent strain. Glyoxal was similar to 1 0 times more toxic than glycolaldehyde and was more toxic to the SOD-null s train than to the parental strain. 1,2-Diaminobenzene protected against the toxicity of glycolaldehyde, These Escherichia coli strains contained the g lutathione-dependent glyoxalases I and II, as well as the glutathione-indep endent glyoxalase III. Of these enzymes, glyoxalase III was most abundant, and it was inactivated within the aerobic SOD-null strain and also in extra cts when exposed to the flux of superoxide and hydrogen peroxide imposed by the xanthine oxidase reaction. Thus, it appears that short chain sugars ar e oxidized by superoxide yielding toxic dicarbonyls, Moreover, the defensiv e glyoxalase III is also inactivated by the oxidative stress imposed by the lack of SOD, thereby exacerbating the deleterious effect of sugar oxidatio n.