The exact mechanism of the increased susceptibility to poisons of the liver in the protein-depleted dog, rat, and human remains obscure.A previous report (1) raised the question of a general loss of activity of the liver enzymes as being the result of protein depletion.But without a knowledge of the precise mode of action of such toxic agents as chloroform, it is not possible to focus a study on the immediate problem.However, the effect of protein depletion on enzyme activity in general seems fundamentally important enough to warrant a study of the effect of inanition and the resulting liver protein depletion on a number of liver enzymes.Addis et al. (2) have systematically studied the tissue protein lost by the rat during fasting for periods up to 7 days, in which time the liver may lose 40 per cent of its protein.Kosterlitz (3) has extended the study to include and correlate changes in liver phospholipide and nucleoprotein.Kaplansky et al. (4) have described the decrease of deaminating, transaminating, and glycogen-forming functions in protein-depleted rats.This report presents data on changes in activity in rat liver enzyme with acute inanition induced by a 7 day fast.The enzymes studied were selected because they represent enzymes of different functional classes, because their intracellular distributions differ, and because their activity may be measured in multiple fashion without manometric techniques.The observed changes in catalase, alka.linephosphatase, xanthine dehydrogenase, and cathepsin activity parallel or exceed the loss of liver protein.It thus appears that the biochemically functional proteins of the liver cell (i.e., the enzymes) are sacrificed along with cell proteins in general.These findings relate to a number of important questions concerning (1) the metabolic relation of enzymes to recognized morphologic structures of the liver cell, (2) the relative stability of intracellular enzyme proteins under conditions of organ protein catabolism or loss, (3) the importance of dietary protein in maintaining not only the integrity of organ protein in general
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Leon L. Miller (1948) studied this question.
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