On the other hand, guanase, also a deaminising enzyme, is in man to be detected in the kidney, lung, and liver, but not in the pancreas or spleen. In the pig, however, guanase is lacking, and its absence no doubt explains why deposits of guanine may occur in the muscles constituting the so-called guanine gout met with in swine. It is worthy of note also that in pigs’ urine the content of purin bases exceeds that of uric acid.
To sum up, in man the enzyme, xanthine-oxidase, which forms uric acid from xanthine, is located chiefly or exclusively in the liver. This, of course, represents the final stage of purin metabolism, but the antecedent chemical processes involved in the disruption of nucleic acids are initiated by the action of enzymes in the intestinal juices and wall, and to a consideration seriatim of these changes we now proceed.
Stages in Disruption of Nucleic Acid
As might be expected from the complex structure of the nucleic acid molecule, a number of ferments are concerned in its disruption. The gastric and pancreatic juices contain not a trace of any enzymes. Thus, when nucleo-protein is subjected to the gastric juice a moiety of protein is readily split off and hydrolysed to peptone and other products of proteolysis.
But the nuclein element remains unacted upon until it comes under the action of the pancreatic juice. Hydrolysis then ensues, and the ingested nuclein is broken down into nucleic acid and protein. The nucleic acid remains unaffected by the pancreatic juice, but, coming in contact with the succus entericus, it undergoes partial decomposition through the action of a ferment called nuclease or nucleic-acidase. Under its disruptive effect the nucleic acids or poly-nucleotides are further split up into groups known as nucleotides. The two pyrimidine nucleotides split off and undergo no further change. But, through the action of another ferment, nucleotidase, the purin nucleotides are further decomposed to yield nucleosides (substances of the glucoside class made up of a combination of a purin base with a carbohydrate group of the nucleic acid with which also phosphoric acid is linked).
No further stage in hydrolysis of nucleic acid occurs in the intestine, but the nucleosides are again in turn split up after reaching the tissues, particularly in the spleen, liver, and thymus. This, under the action of specific enzymes, nucleosidases, which succeed in breaking the nucleosides down into the so-called “building stones” of the nucleic acid molecule, phosphoric acid group, carbohydrate group, pyrimidine and purin bases, especially adenine and guanine. The adenine and guanine thus formed are, by the action of the ferments adenase and guanase, converted and, by the removal of their amino group, transformed, adenine into hypoxanthine, and guanine into xanthine, thus:—
By the action of oxidases also present in the tissues hypoxanthine is changed into xanthine and xanthine into uric acid (trioxy-purine), this by a specific ferment xanthine oxidase.
Scheme Illustrating the Probable Stages in the Passage of Purin through the Body (Walker Hall)