150 SUBCELLULAR PARTICLES 



the synthetic implications of protein or nucleic acid turnover, but their catabolic 

 counterpart has hardly been considered. Investigations dealing with this problem 

 are those of Reid and co-workers ( 76, 75, 91, 77, 78), who have attempted to 

 correlate some enzymic and metabolic changes occurring in the liver and kidneys 

 of hypophysectomized or adrenalectomized rats. Their results are very complex, 

 and the original publications should be consulted for details. Most relevant to the 

 subject of the present review were the increases observed by the authors in the 

 acid ribonuclease and deoxyribonuclease activities of the supernatant fraction after 

 adrenalectomy. In liver, the ribonucleic acid content of this fraction and its rate of 

 labeling from C^* orotic acid were increased, whereas other fractions showed a 

 decreased rate of synthesis of ribonucleic acid and of protein. It is difficult to assess 

 the significance of these results, especially since the increased synthesis of ribonu- 

 cleic acid in the supernatant fraction preceded the rise in unsedimentable ribonu- 

 clease activity. It should be noted that this rise was not accompanied by a similar 

 increase in unsedimentable acid phosphatase (78). This is in contrast with all the 

 results of a similar nature obtained in our laboratory. 



As will be mentioned below, an increase in the unsedimentable activities of the 

 lysosomal enzymes has been observed in the livers of starved rats. However, it is 

 not known to what extent the loss of protein and ribonucleic acid which occurs 

 in starvation is due to decreased synthesis or increased autolysis. According to 

 Laird, Barton and Nygaard (60), the anabolic capacity of the liver is much de- 

 pressed after 6 days' starvation. 



Of interest in connection with these problems are the experiments of Simp- 

 son (88), who found that the release of radioactive amino acids which occurs in 

 isolated liver slices from animals previously treated with these amino acids is 

 inhibited by lack of oxygen, by cyanide and by 2,4-dinitrophenol. These results 

 have been confirmed by Steinberg and Vaughan (go), who have observed that the 

 inhibition is also produced by the amino acid analogues o-fluorophenylalanine and 

 ^-2-thienylalanine, but not by S-methylcysteine. They conclude that protein break- 

 down as it occurs under the conditions of these experiments is not the result of a 

 simple proteolysis but is in some way energy-dependent and linked with protein 

 synthesis. This phenomenon has been further investigated on isolated fractions by 

 Korner and Tarver(54) who have found that dinitrophenol inhibits the release 

 of amino acids in nuclear and mitochondrial fractions but actually increases it in 

 microsomes, while ATP, especially when added with phosphocreatine or 3-phos- 

 phoglycerate, depresses this release in all fractions. The authors point out that the 

 results are very difficult to interpret without separate knowledge of protein syn- 

 thesis and breakdown, and of the specific activities of the amino acids in the frac- 

 tions. It is obvious that these observations, while indicating that cathepsins may 

 not be the sole agents of protein breakdown, do not demonstrate that these 

 enzymes do not play a role in this process. From what is known of the pH 



