326 2. ANALOGS OF ENZYME REACTION COMPONENTS 



It is likely that the same enzyme is responsible for the hydroxylation of 

 both phenylalanine and tryptophan, since the K^ for phenylalanine is close 

 to the iii,,, when it is the substrate; the affinity for tryptophan is, however, 

 much less. These results may help to explain some of the changes observed 

 in phenylpyruvic oligophrenia (see pages 329 and 429). 



Tryptophan-Activating Enzyme 



An activating enzyme from pancreas is specific for tryptophan with 

 respect to other normal amino acids but can activate certain analogs of 

 tryptophan (Sharon and Lipmann, 1957). The analogs tested fall into three 

 categories: 



Group I are activated (tryptazan, azatryptophan, 5-fluorotryptophan, 

 and 6-fluorotryptophan). 



Group 11 are inhibitory (tryptamine, D-tryptophan, /5-methyltryptophan, 

 5-hydroxytryptophan, 5-methyltryptophan, and 6-methyltryptophan). 



Group III are inactive (indole, indoleacetate, 6-methyltryptazan, and 

 iV-acety Itry ptophan ) . 



CH,— CH ^-^ ^ CH^— CH 



^coo' f H H coo' 



N N N 



I I 



H H 



r 



Tryptazan Azatryptophan 



Reciprocal plots were said to indicate competitive inhibition but actually 

 do not show pure competition, and it might better be designated as partially 

 competitive inhibition. For analogs to be activated they must match the 

 size of tryptophan, and the introduction of bulkier groups prevents reaction 

 with ATP but allows binding and inhibition. Azatryptophan and tryptazan 

 are both incorporated into proteins. In E. coli, azatryptophan permits syn- 

 thesis of proteins and nucleic acids but many of the enzymes are not in 

 the normal forms (Pardee and Prestidge, 1958). The synthesis of adaptive 

 enzymes, such as /?-galactosidase, is inhibited very rapidly, and phage for- 

 mation is blocked more readily than bacterial growth. The induced synthe- 

 sis of maltase in yeast is also very potently suppressed by tryptazan, in- 

 corporation of all amino acids being simultaneously blocked (Halvorson 

 etal., 1955). 5-Methyltryptophan and 6-methyltryptazan inhibit moderate- 

 ly, while 6-methyltryptophan is inactive. 



