THE INDIVIDUAL PURINES Uric Acid.—This was the first purine known, being discovered in human urinary calculi by the Swedish chemist Scheele in 1776. Scheele made careful investigations of its reactions and properties, these results being still used to identify uric acid. Thirty years later it was found that uric acid occurred in guano, and still later it was found that birds' excrement consisted largely of uric acid. Guano consists of the excrement of certain South American sea birds, which, with the help of a dry climate, has been ac cumulating for untold years. By far the best source of uric acid, however, is the excrement of serpents, which consists of over 95% of uric acid combined with small amounts of potassium and ammonia. It is only necessary to dissolve snakes' excrement in dilute alkali, filter, and reprecipitate with mineral acid.
Uric acid, however, occurs in other ways. As the mono-sodium salt it is the substance precipitated in body tissues in cases of gout, and is responsible for the formation of the gouty nodules with the subsequent inflammation and irritation which characterize this disease. Uric acid also occurs normally in the blood of man and other animals. In man the blood normally contains less than 0.1 mg. per cu. cm. Uric acid confines itself to the animal king dom, although other purines are common as plant products.
The following table (Givens and Hunter) shows the variation in the relative amounts of allantoin, uric acid and bases (other purines) excreted in the urines of different species of mammals.
Man stands out as eliminating 90% of his purine-allantoin nitrogen in the form of uric acid, this proportion being 11 times as much as the monkey, which is biologically his closest relative. Too much importance must not be attached to the biological significance of this, however, as the ratio is known to vary con siderably, even within a species.
The origin of uric acid as an excretory product has long been a matter of interest. According to A. P. Mathews (Physiological
Chemistry, New York, 1915), the reason for the excretion of pro tein nitrogen in the form of uric acid rather than urea by birds and reptiles, is to be ascribed to their environment during evolution. The birds were evolved from the reptiles, and the reptiles were probably evolved in a dry, arid region, as indicated by other body characteristics. Urea is very soluble in water, and has a great af finity for it, whereas uric acid is insoluble, with no affinity for water, so that the excretion of nitrogen as uric acid rather than urea, saves much water for the organism, and would be an import ant adaptation in a region comparatively devoid of water.
In man the excreted uric acid may be divided into two varieties, the endogenous and the exogenous uric acid. The endogenous uric acid, about 0-4 grams a day, is very nearly constant for a given individual, but varies slightly in amount in different persons. It represents the uric acid which is formed in the body by syn thesis and by the breakdown of nuclear tissue. On a diet which is free from purines, it is independent of the amount of fat, carbo hydrate, protein or number of calories ingested. It is thought to originate from the oxidation of the hypoxanthine constantly formed in muscle and other tissues.
The exogenous uric acid is that formed by the oxidation of purines taken in as part of the food, chiefly in meat. All meat, and particularly glandular meat such as liver and sweetbreads, contains varying amounts of nucleic acid, which contains about 20% of the purines guanine and adenine. In the body these two substances are changed, by means of enzymes, into two other purines, xanthine and hypoxanthine, which are both oxidized to uric acid. The amount of exogenous uric acid depends, then, on the purine intake. Furthermore, it has repeatedly been shown that uric acid and other purines, injected hypodermically into the body, can be recovered nearly quantitatively in the urine.