Gout, with a section on ocular disease in the gouty

by Llewellyn J. Llewellyn

In addition, like results followed the ingestion of the dicarboxylic amino-acids (glutaminic and aspartic acids), the increase in endogenous uric acid excretion being even more pronounced than with glycocoll or alanine.

Now, it must be recalled that the amino-acids represent the end-products of protein digestion. Accordingly, Lewis and his co-workers argue that “since no digestive processes are required for the utilisation of amino-acids, it can hardly be considered that the rises in endogenous uric acid observed following the ingestion of four different amino-acids can be attributed to the work of the digestive glands.” The effect, they held, is more probably attributable to “a direct stimulation of the body cells by amino-acids or their katabolism products, a stimulation of nuclear metabolism,” for it is known that amino-acids disappear very swiftly from the blood-stream to be stored up temporarily in the tissues.

The question that now confronted the observers was whether the stimulation of nuclear metabolism was an inherent property of amino-acids. If so, “substituted amino-acids might be expected to exert a similar influence.” But, if on the contrary, it was due not to the amino-acids as such but “either to the cellular work of their katabolism or to the intermediary products of their breakdown, a substituted amino-acid which does not follow the normal path of amino-acid catabolism would in all probability be devoid of the power of stimulation.”

To this end, they selected sarcosine or methyl-glycocoll to elucidate the point at issue; this, inasmuch as it has been found to pass through the organism for the most part unchanged. The result justified their inference, for no perceptible influence on uric acid excretion was noted. Hence, on the basis of this experiment, they inferred that the stimulation of uric acid metabolism was not an inherent property of amino-acids; in other words, that if an amino-acid when ingested does not undergo disruptive katabolism, it is without effect on uric acid excretion.

Now deaminisation is the first stage in the katabolism of amino-acids, yielding as products ammonia and a-ketonic or hydroxy acids. The ammonia thus formed normally undergoes conversion into urea and is excreted as such. In order to ascertain whether the ammonia stimulated uric acid excretion, ammonium chloride was administered, but no rise in the uric acid output above the normal level ensued. Also, the ingestion of urea seemed to entail no appreciable increase in the uric acid elimination; in other words, these katabolic products of the nitrogenous moiety of the amino-acids are without effect. As to the non-nitrogenous intermediary products of the katabolism of amino-acids, i.e., the a-ketonic or hydroxy acids, it was impossible to investigate the influence of these on the endogenous uric acid elimination.[14]

Lusk also has brought forward evidence that in the presence of amino-acids cellular activities are intensified markedly. According to Taylor and Rose, too, not only nuclear katabolism, but also nuclear anabolism, may be accelerated by the presence of large amounts of amino-acids.

Lewis and his collaborators consider that the results of their researches militate against Mares’ hypothesis, viz., that the origin of the increased amounts of endogenous uric acid that follow the intake of purin-free protein stuffs is referable to intensified activity of the digestive glands.

They hold that “it can be accounted for equally well as the result of a general stimulation of all cellular metabolism by the products of digestion of proteins the amino-acids.”