The physiological derivation of uric acid from nucleic acid did not long lack experimental proof. In 1886 Minkowski found that, given extirpation of their livers, the urine of birds contained ammonium lactate, evidently a substitute for the uric acid normally present, notwithstanding the uric acid never entirely disappeared from the urine. This indicated the derivation of uric acid from two sources:—
- (1) Conversion in the liver of ammonium lactate into uric acid.
- (2) Some other, though unknown, process of formation.
To clear up the obscurity regarding the latter, V. Mach, after extirpating the livers of geese, injected them subcutaneously with hypoxanthine, finding that the same was converted into uric acid, which was excreted in the urine. In this way the capacity of the organism to elaborate uric acid from a purin precursor was demonstrated.
Uric Acid a Derivative of Nucleic Acid
Despite V. Mach’s revelation, the origin of uric acid from nucleic acid was still to seek. In the year following (1889) Horbaczewski traced it to this source, and in the following manner. Mixed with water, the pulp of the calf’s spleen was put to digest at 50° until putrefaction began. The fluid was then sterilised with a solution of lead acetate, and arterial blood being added it was kept at 50°, a current of air meanwhile being passed slowly through the mixture. Subsequently the fluid was found to contain uric acid; but the experiment being repeated, without the passage of air, xanthine and hypoxanthine and not uric acid resulted.
While Horbaczewski’s experimental findings were amply confirmed, some of his deductions therefrom were subsequently proved faulty. (Thus, he thought putrefaction an essential factor; also he believed that the formation of uric acid ensued before the purin groups were disengaged from the nucleic acid, and definitely affirmed that the uric acid was not produced by the oxidation of free xanthine or hypoxanthine.)
But, nevertheless, this pioneer established that in both man and rabbits uric acid was derived from nucleic acid. Also, having observed that when after starvation the food intake was resumed, a leucocytosis occurred, he announced his belief in the following theory. Thus, he noted that leukæmics, whose blood showed a high leucocyte count, excreted an unusually large amount of uric acid; consequently, he came to the conclusion that uric acid was formed from defunct leucocytes. Also that nuclein-rich food, when ingested, contributed to the formation of uric acid only in so far as it induced leucocytosis. Hence the origin of the increased uric acid excretion which occurs when feeding is resumed after starvation.
This increased excretion of uric acid after the ingestion of food rich in nucleic acid has been amply confirmed; but all the earlier attempts to achieve an increased excretion by the ingestion of free purin bases, as opposed to the combined purin bases, existing as such in nucleic acid, failed, although tried repeatedly.
So much for the various stages by which our knowledge of the purin derivatives of nucleic acid has been gradually acquired, for though purin bases had, from early times, been known to exist in animal tissues, their presence there could not be rationally accounted for prior to the discovery of nucleic acid.
It still remains for us to deal in detail with the further developments of our knowledge which concern the disruption of nucleic acid in the body and the process by which uric acid is derived therefrom.