The final product of the purine metabolism differs in the various animal species; only the dalmatian dog and the primates excrete uric acid in the urine, as man does. For over a year seven female dalmatian dogs have been used in a study on different methods of lowering the uric acid excretion. Uric acid derives from the oxidation of xanthine through a reaction catalyzed by xanthine oxidase. Four possible ways of interfering with this reaction were experimented, in order to lower the uric acid which reaches the kidneys and is excreted. I. Lessen the enzyme available. Xanthine oxidase has in its molecule molybdenum, which is necessary for the enzyme activity. The administration of tungsten which issimilar to molybdenum, causes a lowered enzymatic activity. This action of tungsten, formerly described by Sorrentino in man, has been confirmed in the dalmatian dog. II. Interfere with the xanthine enzyme reaction using a great amount of an anti-metabolite of xanthine, allopurinol, which by a mass action blocks the reactive sitesof the enzymatic molecule, excluding them from contact with xanthine. By means ofsuch a mechanism, allopurinol is able to provoke a lowered uricosuria. III. Bind the uric acid as soon as it is being formed, to prevent it from entering the kidney in an eliminable form. The anti-uric acid antibody production could theoretically fulfill this goal, but in practice the immunization induced in the dalmatian dog does not interfere with the uric acid excretion. IV. Block the xanthine oxidase inducing the production of anti-enzyme antibodies. Immunization against milk xanthine oxidase causes no changes of uricosuria. In the final analysis, both tungsten and allopurinol are able to lessen the uricosuria in the dalmatian dog. Tungsten shows its action after a latency period which is longer than allopurinol, and causes a greater and longer lasting lowering of uricosuria. Allopurinol acts much faster, but its action disappears rapidly.

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© 1970 S. Karger AG, Basel
1970
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