REDUCTION AND BINDING OF ARSENATE AND DIMETHYLARSINATE BY GLUTATHIONE- A MAGNETIC-RESONANCE STUDY

By observing the chemical shifts of the proton and carbon-13 nuclei of reduced glutathione, the interactions of arsenate, arsenite and dimet hylarsinate with this tripeptide have been characterized. These spectr al studies show the reduction and complexation of arsenic to be a two- step process. Initially, the oxidation of 2 mol of glutathione reduces arsenate to arsenite. Then, 3 mol of glutathione are consumed in the formation of a glutathione-arsenite complex. Similar experiments with arsenite identified a (glutathione)3-arsenite complex; however, no oxi dized glutathione was detected. The arsenite binding site in the gluta thione-arsenite complex is the cysteinyl sulfhydryl. The glutathione-a rsenite complex is stable over the pH range from 1.5 to 7.0-7.5. At hi gher pH, dissociation occurs releasing reduced glutathione. For a glut athione to dimethylarsinate ratio of 3, oxidized glutathione is also c oupled with a reduction to trivalent dimethylarsinous acid, prior to t he formation of a 1:1 glutathione-dimethylarsinite complex. The role o f reduced glutathione in the metabolism of arsenic is consistent with the previously described effects of this agent on the organismic toxic ity of arsenic.