Purin Metabolism in other Disorders
Working at the Research Hospital for the Study of Special Diseases at Cambridge, Strangeways (1910) commented on the striking resemblance that obtained between certain cases of so-called rheumatoid arthritis and gout, as evidenced by X-ray findings and section of the joints. Their similitude in these respects suggested that the nature of the apparent kinship of the two disorders might be elucidated by a study of purin metabolism in instances of rheumatoid arthritis.
To this end Ackroyd studied the purin metabolism in eleven persons, the victims of rheumatoid arthritis. His conclusion was that there was no important variation from the normal. To quote his own words, he states that “it may be (1) completely normal, or (2) while normal as regards endogenous excretion, the period of increased uric acid excretion which follows the administration of hypoxanthine may be prolonged for more than four days. It is more likely that this effect is individual, than that it is characteristic of any particular form of the disease, excepting those cases in which the prolongation is accompanied by active manifestation of the disease.”
W. J. Mallory, critically analysing Ackroyd’s cases, points out that he used only hypoxanthine in his studies; also that, while hypoxanthine has this advantage, that it is of definite and known chemical composition, furnishing a known quantity of basic nitrogen, it labours under this drawback: “It is by simple oxidation converted into uric acid, and probably calls into action only a limited part of the ferment system concerned in the formation of uric acid.” As a consequence, therefore, the amount of information on metabolism that can be gleaned through its usage is more restricted than if nucleinic acid were invoked in its place; for this substance, on the other hand, calls into action all the various enzymes concerned in the disruption of nuclein or nucleic acid.
Alive to these advantages, Mallory, in addition to hypoxanthine, used nucleinic acid in his investigations of purin metabolism in a series of eight “undoubted cases of so-called rheumatoid arthritis.” The value of the inclusion of nucleinic acid is revealed by the fact that some of the cases, when given exogenous purin in the form of hypoxanthine, showed no deviation from the normal. On the other hand, when given nucleinic acid, a prolongation of the period of increased uric acid excretion ensued; this even though the total amount of basic nitrogen in nucleinic acid is less than in hypoxanthine. Thus 4 grams of nucleinic acid have 0·2632 gram of basic nitrogen, while 0·75 gram hypoxanthine has 0·309 gram of basic nitrogen.
Apart from his own series of cases, Mallory analysed those of other observers, and his conclusions are as follows: “Of nineteen cases of rheumatoid arthritis in which the purin metabolism has been studied by three different observers, nine cases, or 47·3 per cent., show a marked variation from the normal in their reaction to purin-containing substances while they are on a purin-free diet.
“In these cases the period of increased uric acid excretion which follows the administration of purin-containing substances is much prolonged. Following the administration of purin-containing substances, a considerable number of cases suffer from attacks of sub-acute arthritis, accompanied in some cases by an increased uric acid excretion.”
It will be seen that in virtue of:—
(1) The prolongation of the period of exogenous uric acid excretion, and
(2) Increased uric acid excretion during attacks of sub-acute arthritis,