The Mechanism of Cysteine and Glutathione Protection Against Alloxan Diabetes

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Abstract
Alloxan is rapidly decomposed at pH 7.4. It is also reduced to dialuric acid by sulfhydryl compounds. In absorption spectra studies, the formation of a maximum with alloxan and glutathione at 305 millimicrons is striking, and may be due to the formation of an addition product. Since addition of cysteine converts alloxan to dialuric acid, the fact that added cysteine slows down the formation of a product with an absorption spectrum maximum at 305 millimicrons indicates that the mechanism involves a reaction of glutathione with alloxan rather than with dialuric acid. Since glutathione fails to react, the addition product may take place through the sulfhydryl group of the glutathione. The mechanism by which cysteine protects against alloxan diabetes is due to the reduction of alloxan to dialuric acid. Although dialuric acid can be reconverted, this reconversion is slowed by cysteine. Glutathione removes alloxan from action by forming a new compd. with an absorption spectrum maximum at 305 millimicrons. The data support the view that dialuric acid itself is not diabetogenic. The diabetes after its injn. is due to the conversion of dialuric acid to alloxan.

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