A study of xanthine metabolism in the rat.

Par many years it has been known that purine catabolism in the rat results in the formation and subsequent urinary excretion of allantoin as the main end-product. Individual enzymes catalyzing the steps in purine catabolism have been identified and methods for assaying these enzymes in vitro have been developed. With the discovery that xanthine oxidase activity in vitro is influenced greatly by the level of dietary protein (l-3) a means was offered for directly comparing the activity in vitro of the enzymes involved in xanthine catabolism with activity of those enzymes in the intact animal. In rats on low protein diets it has been observed that liver xanthine oxidase activity as measured in vitro is greatly decreased, in many cases disappearing entirely, if the dietary protein level is reduced sufficiently. If xanthine oxidase rather than uricase limited the rate of breakdown of xanthine to allantoin, animals with low xanthine oxidase activity should convert xanthine to allantoin at a slower rate than animals with normal xanthine oxidase activity. If not, then measurements in vitro of xanthine oxidase activity may not be taken as an indication of the actual rate of xanthine oxidation in the intact animal. This problem was studied by placing animals on a ration known to decrease xanthine oxidase activity in vitro, by injecting them with a known amount of xanthine, measuring the rate of allantoin excretion in the urine, and finally assaying the tissues of the rats for xanthine oxidase and uricase activity. The urinary excretion of other purines from the animals with xanthine injected was also measured in an attempt to account for all of the injected xanthine either as allantoin or purine. The xanthine was injected rather than fed, since dietary xanthine would probably be incompletely absorbed from the intestinal tract because of its relatively low solubility. In that case quantitative relationships between the amount of xanthine ingested and catabolites excreted could not have been made.