The Relation of Amino Acid Availability in Dietary Protein to Liver Enzyme Activity*

In 1948 Miller (1) demonstrated that the loss of liver xanthine oxidase activity in the rat greatly exceeded the loss of liver protein during acute inanition. Moreover, xanthine oxidase appeared to be the most labile of the four liver enzymes studied. Westerfeld and Richert (2) observed that increasing the level of protein in the diet tended to bring about an increase in liver xanthine oxidase activity, although there was no direct correlation between the level of dietary protein and enzyme activity. Because of the apparent lability of liver xanthine oxidase, the present work was undertaken to observe whether the measured activity of this enzyme could be used as an index of general protein metabolism. In this work the question of availability of amino acids in dietary protein has been related to liver xanthine oxidase activity under conditions in which gross body changes are not in general sensitive enough to reflect small protein variations in the animal body. It has been found that, at a level of whole dietary protein which maintains and even supports growth of the adult rat, liver xanthine oxidase activity may be appreciably decreased, probably because of incomplete assimilation of the amino acids in the protein. Early in the experiments it was observed that animals fed a 14.6 per cent casein diet exhibited much lower liver xanthine oxidase activity than rats fed a good stock ration. It was also observed that if the animals were fed acid-hydrolyzed casein at an 18 per cent level (isonitrogenous with 14.6 per cent casein) the xanthine oxidase activity based on liver protein was also much higher than that in animals fed the 14.6 per cent casein diet. If the animals were unable to digest completely the ingested whole protein, the poor availability of one or more essential amino acids could account for the low xanthine oxidase activity. On the other hand if the protein were fed in a predigested form, i.e., as acid-hydrolyzed casein, this difiiculty should not be encountered and xanthine oxidase activity should be normal. To rule out the possibility of the formation of unknown factors