Organic Combinations
It will be recalled that purin bodies cannot be detected in the blood in health, though their administration by the mouth results in an increase in the excreta. Minkowski, to account for this, suggested that the purins in the blood were circulating in a combination which prevented them from giving the usual reactions, typical of their presence therein. We have an analogy in the masking of arsenic and iron in the cacodyl compounds and the ferrocyanide ion.[8]
The explanation proffered by Minkowski was elaborated by Von Noorden. His view was that lying at the disposal of the normal organism are a certain number of organic substances. These latter can combine with uric acid and render it soluble. It is then in this form passed through the blood in the kidneys, which eliminate from it the uric acid. Now, in gout these organic substances are deficient or wanting, and the result is that the uric acid is passed into the blood in the form of urates, the elimination of which only proceeds with difficulty; in other words, the purins normally circulate in organic combination and abnormally as salts of sodium.
It is worthy of note that, from a solution containing albuminous substances, Burian and Walker Hall found that while it was easy to remove the bulk of the purins, a certain percentage always remained which it was difficult to extract.
The view that uric acid is probably carried in the blood in combination with some other organic body and not, as was formerly supposed, with sodium salts, rapidly gained adherents, but the nature of the organic complex is still not accurately known. Many believe that at least a moiety of the uric acid circulates in combination with nucleic (thyminic) acid, but no such compound has yet been isolated from the blood. Nevertheless, as MacLeod suggests, this theory, were it proved correct, would account for the fact that some purins at least are katabolised in the body when they are given in a combined state, as thyminic acid, but are excreted unchanged when ingested in a free state. Thus, certain purins, e.g., adenine, when given freely, cause inflammation and calculous deposits in the kidneys of dogs which, however, does not ensue when they are fed with thymic acid.
But Walker Hall, discussing the good results obtained by Schmoll and Fenner from the administration of thyminic acid, states that his experiments do not indicate that the improvement is at all associated with any change in the uric acid excretion.
To sum up, it is obvious, from the mere variety of the hypotheses advanced, that we are still much in the dark as to the actual form in which uric acid circulates in the blood. While on the one hand the quadriurate theory appears no longer tenable,[9] on the other the nature of the suggested uric acid organic complex is still unknown.
Nay, more, Walker Hall, writing in 1913-14, states “there are many who consider that the sodium mono-urate is the only possible compound;” while Wells, in his “Chemical Pathology” (1918), claims that the best evidence points to uric acid existing in the blood “in a free state and not combined, as was at one time urged by several students of gout.”