140 THE BIOSYNTHESIS OF PROTEINS 



enzyme activity in animals. The system which has best been studied from 

 the biochemical point of view is the stimulation of tryptophan peroxidase 

 activity of rat liver. It was soon observed (Knox, 1951) that an increase of 

 this enzyme activity can be obtained not only by tryptophan, but also by 

 the injection of histidine or of adrenaline. Adrenalectomy reduces the 

 normal basic level of the enzyme. Due to this and other hormonal actions, 

 involved controlling effects are observed. Cortisone and hydroxycortisone 

 stimulate the production of the enzyme (Knox and Auerbach, 1955). 

 Adrenocorticotropic hormone (ACTH) stimulates peroxidase activity, and 

 hypophysectomy depresses it. This effect of ACTH is probably mediated 

 through the steroid hormones since ACTH causes the synthesis of corti- 

 costeroids (Koritz et ah, 1957). Reserpin (Canal et ah, 1959) and insulin 

 (Schor and Frieden, 1958) also increase the level of the enzyme. The stimu- 

 lating effects of tryptophan and of insuline or hydroxycortisone are 

 additive, as if these agents were acting in different ways (Civen and Knox, 

 1959; Schor and Frieden, 1958). 



Increase in tryptophan peroxidase activity was obtained in isolated 

 perfused liver (Price and Dietrich, 1957) and in liver slices (Ephimotchkina, 

 1954). Such systems make it possible to avoid the hormonal effects. Even in 

 cell-free systems, an increase of tryptophan peroxidase was caused by 

 tryptophan (Clouet and Gordon, 1959), but the increment of enzyme 

 activity was correlated with changes in permeability of the mitochondria, 

 which strongly suggests that the increase in activity might reflect changes 

 in the accessibility of the enzyme rather than an actual de novo synthesis 

 (Gordon and Rydziel, 1959). There were indications that a net synthesis 

 of tryptophan peroxidase occurs during in vivo induction by tryptophan 

 (Gros et al., 1956). On the other hand, convincing evidence was recently 

 obtained that substrate induction of this enzyme activity may be due — at 

 least in part — to an intracellular translocation of the enzyme or of an 

 activator (Greengaard and Feigelson, 1960); this reminds one of certain 

 observations by Lee and Williams (1953) pointing in the same direction. 

 It is therefore doubtful whether tryptophan peroxidase 'induction' has 

 anything in common with the induced synthesis of enzymes as observed in 

 micro-organisms; it might be a case of adjustment of the activity of pre- 

 existing enzyme systems. This may explain the rapid disappearance of the 

 enzyme activity during deadaptation (Feigelson et al., 1959). 



The activity of tyrosine a-ketoglutarate transaminase can also be 

 increased by injecting tyrosine or hydroxycortisone (Lin and Knox, 1958). 

 It would seem at present that the increase rests on a process of activation or 

 release and not on protein synthesis, as shown by experiments combining 

 the use of labelled amino acids and the serological isolation of the enzyme 

 (Kenney, 1960). 



One should therefore be very careful in assimilating these effects with 



