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 dimethylarsinate with this tripeptide have been characterized. These spectral 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 oxidized glutathione was detected. The arsenite binding site in the glutathione-arsenite complex is the cysteinyl sulfhydryl. The glutathione-arsenite complex is stable over the pH range from 1.5 to 7.0-7.5. At higher pH, dissociation occurs releasing reduced glutathione. For a glutathione to dimethylarsinate ratio of 3, oxidized glutathione is also coupled with a reduction to trivalent dimethylarsinous acid, prior to the formation of a 1:1 glutathione-dimethylarsinite complex. The role of reduced glutathione in the metabolism of arsenic is consistent with the previously described effects of this agent on the organismic toxicity of arsenic.
Delnomdedieu
M
M
Center for Environmental Medicine, University of North Carolina, Chapel Hill 27711.
Basti
M M
MM
Otvos
J D
JD
Thomas
D J
DJ
D001149:Arsenates / Q000737:chemistry / Q000378:metabolism*; D018053:Arsenites / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002101:Cacodylic Acid / Q000737:chemistry / Q000378:metabolism*; D004355:Drug Stability; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010084:Oxidation-Reduction
D001149:Arsenates; D018053:Arsenites; D002101:Cacodylic Acid; D005978:Glutathione; C015001:arsenite; C025657:arsenic acid