324 2. ANALOGS OF ENZYME REACTION COMPONENTS 



tion) (Gooder and Happold, 1954). The importance of the indole N in 

 binding is indicated by the weak inhibition with the last analog (tryptophan 

 with the indole N methylated) and the failure of indene (the hydrocarbon 



/ 

 .CHoCOO" /\ /CH,— CH 



NH^ 



IJ COO' 



N' "^ N 



I I 



H CH3 



3-Indolylacetate 0-1 -Methyl- 3 -indolylalanine 



.CHoCHoNH, 



N 

 I 

 H 



0-3-Indolylethylamine 



analog of indole) to inhibit, while the importance of the carboxylate group 

 is reflected in the weak inhibition by the indolylethylamine. The potency 

 of indole may be attributed to the fact that it may not have to be oriented 

 in a manner necessary for reaction of the side chain. 



Tryptophan Pyrrolase (Tryptophan Peroxidase) 



This enzyme initiates one of the most important catabolic pathways of 

 tryptophan and is readily inhibited by certain analogs. Hayaishi (1955 b) 

 found the Pseudomonas enzyme to be sensitive to the hydroxytryptophans, 

 and calculated the values of K; shown in the following tabulation. Since 



Substance 



Ki or Kg Relative — Zli^ of binding 



(milf) (kcal/mole) 



5- Hydroxy tryptophan . 002 8 . 06 



7-Hydroxytryptophan 0.12 5.55 



L-Tryptophan 0.4 4.81 



5-hydroxytryptophan is normally formed from tryptophan on the pathway 

 to serotonin, its potent inhibition of the pyrrolase suggests that it may 

 play a role in regulating tryptophan metabolism. The enzyme from rat 

 liver is also inhibited by 5-hydroxytryptophan and even more potently 



