The Individual Purines

Man excretes ingested purines almost entirely as uric acid, although other mammals excrete theirs almost entirely as allantoin, because the human body is lacking in a specific enzyme, uricase, which oxidizes uric acid to allantoin. The small amount of allantoin excreted by the human is probably preformed in the food. In the livers and other organs of animals which excrete allantoin, we find varying amounts of uricase, and if these organs are ground up and digested with uric acid, it is oxidized to allan toin. Different animals apparently differ in the efficiency with which this reaction is performed.

When the uric acid metabolism is disturbed, for reasons which are not as yet understood, the uric acid output in the urine is lowered. As the individual constantly ingests more purine, the result is that it is stored up. At first this storage takes place in the blood, but owing to the very low solubility of uric acid and its mono-sodium salt, only a limited amount can be held in this way.

The excess crystallizes out, mainly in the cartilages and joints, as acid sodium urate, and the irritation resulting from these de posits is known as gout. It is evident that a gouty person should avoid foods which contain purines, such as meat, and confine his protein diet to such foods as milk and eggs, which are virtually purine free.

Guanine and Nucleic Acid.

Guanine, one of the two amino-purines occurring in nature, takes its name from the fact that it was discovered in guano, by B. Unger in 1845. Since that time, however, it has been found widely distributed throughout the animal and plant world. It occurs in the scales and skin of the bony fishes, and in the swim bladders, to which it gives their characteristic pearly appearance. It also is the chief constituent of the excrement of spiders. Human and pig urine contain small amounts of guanine. By far its most important occurrence, how ever, is in organs rich in cells, such as the pancreas, liver, spleen, testicles, etc., in animals, and in the germ cells of plants. It occurs here as a constant constituent of nucleic acid, of which it con stitutes about '0%.

Nucleic acid, a compound occurring in the nuclei of all cells, is built up from four molecules of phosphoric acid, four of sugar, two of pyrimidines, and one each of guanine and adenine. When taken into the body as food, the guanine and adenine are even tually excreted as uric acid. These changes are brought about by the action of enzymes, which eventually break the nucleic acid up into its component molecules. The guanine is then changed by

an enzyme, guanase, into its corresponding oxygen derivative, xanthine, which is then oxidized by an enzyme, xanthine oxidase, to uric acid.

It is an extremely interesting fact that in the pig the organs are entirely lacking in guanase it is thus impossible for it to change guanine into allantoin, and consequently the pig frequently suffers from a form of gout, similar in all respects to that in hamans, except that the deposit in the joints consists of crystalline guanine instead of acid sodium urate.

Adenine.

Adenine and guanine are the only two amino purines, and differ from one another by only one atom of oxygen, guanine being an oxidized adenine.

Adenine, discovered by A. Kossel in 1884 among the hydrolytic products of pancreatic nucleic acid, is found in all glandular tissues, which are rich in nucleins. In addition, it occurs free in the leaves of plants, for example tea leaves and alfalfa leaves. It has also been found combined with sugar in the blood stream.

Adenine, like guanine, is one of the chief contributors to the uric acid and allantoin output of mammals. After the enzymic cleavage of the nucleic acid there are two special enzymes to take care of the adenine. One of these, adenase, replaces the amino-group by an hydroxyl, giving hypoxanthine. Another en zyme, an oxidase, oxidizes the hypoxanthine to xanthine, which is further metabolized as in the case of guanine.

Xanthine.

This purine, first discovered by Marcet, in 1817, in a urinary stone, derives its name from the Greek word, xanthos, meaning yellow : when it is evaporated in a dish with a yellow spot remains. Xanthine occurs widely distributed in animal and plant matter, wherever guanine is found, being probably derived from guanine by enzymic and putrefactive processes.

Hypoxanthine (Sarcine).

Hypoxanthine is a reduced xan thine, which was discovered by Scherer in 185o in an extract of spleen. In general, it may be found in all nuclear tissues, and is probably there as a decomposition product of adenine, from which it is derived by the substitution of an hydroxyl by an amino-group. This change is brought about by the enzyme, adenase, as a result of either normal degradation or putrefactive processes. It is also found in small amounts in bone marrow.