Metabolism of alloxanic acid in a soil microorganism.

Alloxan is a polyoxy-pyrimidine of unusual biological interest, being the agent of choice for producing experimental diabetes (Shaw-Dunn, Sheehan, and McLetchie, 1943). Despite the fact that it has been used extensively for many years, very little is known of its ultimate fate in mammals or other forms of life. It is exceedingly unstable at physiological pH values and is spontaneously converted to alloxanic acid within a few minutes in blood (Leech and Bailey, 1945; Seligson and Seligson, 1951), or other milieus (Richardson and Cannan, 1929; Archibald, 1945; Patterson, Lazarow, and Levey, 1949). Although mammals receiving alloxan excrete small quantities of murexide (Cerecedo, 1931; Lee and Stettin, 1952) and a compound which yields mesoxalic acid on hydrolysis (Seligson et al., 1951), the major decomposition products would appear to be unidentified substituted urea compounds which arise from alloxanic acid metabolism (Lee and Stettin, 1952). A study of the metabolism of alloxanic acid in a bacterium obtained by soil enrichment was undertaken to establish a route for alloxan catabolism. The method of simultaneous adaptation was used as this technique has been successful in studying the breakdown of related pyrimidines (Wang and Lampen, 1952; Hayaishi and Kornberg, 1952; Lara, 1952). An additional reason for studying alloxanic acid catabolism was the hope that the knowledge gained might suggest means for evaluating the hypothesis that certain cases of diabetes may arise from the endogenous formation of alloxan from various natural precursors. According to this hypothesis (Lazarow, 1946) normal products of metabolism such as uric acid or substances in vegetable foodstuffs may give rise to alloxan under certain conditions. The fugitive nature of alloxan makes it difficult to test this hypothesis