VOL. 4 (1950) 



SPECIFICITY OF DECARBOXYLASES 



135 



R 



H— C— NH2 + 



I 

 COOH 



= C— H 



I 

 C 



— c c — 



II I 



H— C— N = C— H 



I I 



COOH C 



— C C — 



II I 



+ H»0 



It is clear that this reaction will only occur when the amino group is unsubstituted. 

 We conclude that N-methyl-amino-acids are unable to react with the formation of a 

 -N = C( bond. This inability would account for the fact that N-methyl-amino-acids 

 are not substrates of the amino-acid decarboxylases. 



VI. THE BASIS OF SUBSTRATE SPECIFICITY 



The experiments discussed have shown two different types of substrate specificity. 

 DOPA decarboxylase may serve to demonstrate these: 



a. tyrosine is not a substrate of DOPA decarboxylase, because it does not react 

 with the enzyme protein ; 



b. N-methyl-3 : 4-dihydroxyphenylalanine is not a substrate of DOPA decarbo- 

 xylase, because it does not react with the coenzyme. 



DOPA decarboxylase, like all the amino-acid decarboxylases, presents a third type 

 of substrate specificity: specificity for the members of the L series. Holtz, Heise, and 

 LtJDTKE^ suggested already that DOPA decarboxylase was specific for L-dihydroxy- 

 phenylalanine ; we have confirmed this, using the d isomer which was not decarbo- 

 xylated (Bl.\schko^2)_ 



The lack of affinity for the d form is easily understood in the light of the evidence 

 discussed in this review. If we consider the alpha carbon atom of the amino-acid, 



la 



H— C— NH2 

 COOH 



we see that three of the groups attached to this atom take part in the decarboxylation 

 reaction: 



a. the carboxy group, which loses carbon dioxide, 



b. the amino group which reacts with the aldehyde group of pyridoxal, and 



c. the group R which reacts with the enzyme protein. 



If the decarboxylation requires a fixed relationship of these three groups relative 

 to the enzyme, it is clear that the L and D forms are not equivalent ; only one of the 

 stereoisomers can be expected to fulfil the conditions required for decarboxylation. The 

 stereospecificity of other enzymes dealing with amino-acids may have a similar basis 

 (see Rydon^^), but the conditions of specificity are not so completely known. 



It has been pointed out that the presence of a third polar group in R is a common 

 feature of all bacterial amino-acid decarboxylases (Gale^*). The same is true for the 

 mammalian decarboxylases, not only for DOPA decarboxylase, but also for the l- 

 cysteic decarboxylase of mammalian liver (Blaschko^^). 

 References p. 136I13';. 



