The conversion of alloxan to alloxanic acid in plasma.

Since the discovery of alloxan diabetes in 1943 (l), several investigators have discussed the possibility that alloxan might be involved in some way in the pathogenesis of diabetes mellitus. Dunn et al. (1) considered this on the ground that alloxan was chemically related to uric acid. Lazarow (2) reviewed the possible relation of alloxan to diabetes and discussed the pro_ tective mechanism of the sulfhydryl compounds. Conn, Louis, and Johnston (3), having demonstrated that adrenocorticotropic hormone (ACTH) caused a fall in blood glutathione and temporary diabetes in human subjects, compared the action of ACTH to that of alloxan, which also lowers blood glutathione and causes glycosuria. The rapid disappearance of alloxan in plasma (4, 5) makes it necessary to determine quantitatively the end-products in investigating the relation of alloxan to diabetes mellitus. In this paper the decomposition products of alloxan have been studied as a contribution to the problem of the relationship of alloxan to diabetes mellitus. The instability of alloxan has been studied (4-6) and the conversion of alloxan to salts of alloxanic acid in alkali has been described (7-9). Alloxanic acid has been characterized by the elementary analysis of it,s barium salt (8), of its methyl and ethyl esters (7), and by its oxidation to parabanic acid (7). The conversion of alloxan to alloxanic acid has also been followed by means of the hydrogen ion concentration of the reaction (9). Since these procedures are unsatisfactory for use in biological fluids, we have used hydrolytic and oxidative reactions combined with paper chromatography. With these methods, which have not hitherto been applied to this problem, the decomposition of alloxan in buffers and plasma has been studied.