The effects yielded on uric acid excretion by those antithetic drugs, atropine and pilocarpine, certainly seem to lend colour to Mares’ hypothesis.
Following the injection of atropine, the rise in uric acid output, that normally follows the ingestion of protein, was inhibited. But in sequence to pilocarpine, an excitant and not like atropine, a depressor of secretory activity, a marked increase in uric acid excretion followed. The contrast in response was naturally translated as striking evidence of the important rôle played by the digestive glands on uric acid excretion; in other words, it was held that the major portion of the endogenous uric acid was the reflex of such intensified glandular action.
In opposition, however, Burian, as the outcome of his experimental studies, maintained that a fractional portion only of the endogenous uric acid could be derived from the nucleo-protein of the body cells. This, inasmuch as it would entail a far too extensive katabolism of nuclear substance. Accordingly he propounded the view that the endogenous uric acid in the main was derived from the hypoxanthine of the inosinic acid present in muscular tissue. In this connection it may be noted that, on a diet approximating to Voit’s standard, 0·5 gram of purin is excreted daily. This, it is calculated, is equivalent to nearly 100 grams of thymus or allied tissue, which probably far exceeds the amount that could be gleaned from cellular katabolism.
Proteins and their Derivatives
A comparison of the influence of proteins as contrasted with that of their digested products, the amino-acids, it was thought, might furnish a clue as to the extent of which the alleged activity of the digestive glands was responsible for the increased uric acid output that followed the intake of non-purin protein food.
Such was the supposition entertained by H. B. Lewis, M. S. Dunn, and E. A. Doisy. Alive, moreover, to the deficiency of the older procedure in use for the determination of small amounts of uric acid, Lewis and his collaborators invoked the more accurate colorimetric method of Folin and Denis (as modified by Benedict and Hitchcock).
The experiments were conducted with great care, and with as complete control as possible of the variable factors concerned. The investigators realised that, if any significance was to be attached to fluctuations in uric acid excretion following the intake of proteins and their derivatives, it was essential that accurate information be obtained as to the extent of the variations to be expected normally in the subjects when fasting. “Controls,” therefore, in which no food was consumed throughout the experiments, were instituted at frequent intervals so as to make sure that the level of endogenous uric acid metabolism was not altered by the long-continued purin-free diet.[13]
Passing now to the results obtained, it was noted that, after the intake of three types of purin-free protein food (egg white, cottage cheese, and glidine), there ensued a rise in uric acid output, reaching its maximum during the third or fourth hour after their intake. No quantitative differences in the uric acid output after ingestion of these three types of protein were observed; in short, the findings did but confirm what had been repeatedly demonstrated, viz., that the excretion of the endogenous uric acid is increased by purin-free protein food.
Amino-Acids and Dicarboxylic Amino-Acids
But the further interesting fact emerged, viz., that glycocoll and alanine, end-products of protein digestion, also augmented uric acid excretion; moreover, this even more swiftly than proteins, the maximum being reached within two hours after their intake.