Studies on Uric Acid and Related Compounds

The systematic study of the substrate specificity of mammalian xanthine oxidase has indicated a common mechanism by which various purines may be dehydrogenated (1). The results obtained also made it clear why methylated xanthines, with the exception of 1-methylxanthine (2), cannot be oxidized by xanthine oxidase to the corresponding substituted uric acids (3, 4). Therefore, another source had to be sought for these compounds, which appear regularly in the urine of mammals after administration of substituted xanthines (5). It appeared possible that bacterial enzymes are responsible for this metabolic reaction. Our knowledge of bacterial xanthine oxidases is rather limited. Villela, AiYonso, and Mitidieri (6) demonstrated xanthine oxidase in Lactobacillus casei ATCC 7469, and Franke and Hahn (7) tested the activity of Pseudomonas aeruginosa against xanthine and some of its methyl derivatives, all of which were oxidized. Other intestinal strains, on the other hand, were found inactive. The capacity of Mycobacterium smegmatis to convert xanthine into uric acid has been reported by di Fonzo (8). On the basis of these findings, it appeared possible that substituted uric acids are produced by the intestinal flora and absorbed into the general circulation, owing to the fact that they are much more soluble than uric acid itself. Therefore, a systematic study of the ability of the bacterial population in the human intestine to oxidize xanthine and other purine derivatives was undertaken, and the oxidation products were identified in each case by unequivocal methods. Our results differ essentially from those reported by Franke and Hahn (7).