132 H. BLASCHKO VOL. 4 (1950) 



one of two adjacent positions on the benzene ring. The position of this group in the 

 enzyme would be different for the bacterial and the mammalian enzyme, as shown in 

 Fig. I. 



II. 2:5-DIHYDROXYPHENYLALANINE 



This amino-acid has recently been synthetized by Neuberger^. We have examined 

 it and have found that it is a substrate of the mammalian enzyme, but that it is not a 

 substrate of the bacterial enzyme. 



HO HO 



io/ VcHa-CHNHg-COOH ^ VcHg-CHNHa-COOH 



OH 

 3 : 4-dihydroxyphenylalanine • 2 : 5-dihydroxyphenylalanine 



That 2 : 5-dihydroxyphenylalanine is a substrate of the mammalian decarboxylase 

 is easily explained by the hypothesis outlined above ; the lack of affinity for the bacterial 

 enzyme, however, is not obvious; possibly the presence of the hydioxyl group in ortho 

 position interferes with the attachment to the enzyme. 



We have examined both the l and the D forms of this amino-acid ; in agreement 

 with expectation, only the l form is a substrate of DOPA decarboxylase. The product 

 of the decarboxylation reaction, /3-2 : 5-dihydroxyphenylethylamine, seems to be a 

 substrate of amine oxidase ; this suggests that in the living animal it is metabolized as 

 follows : 



HO_ 



^ -CH,-CHNH„-COOH 



OH 



L-2 : 5-dihydroxyphenylalanine 



HO 

 /"^CHg-CHa-NHg 



OH 

 ^-2 : 5-dihydroxyphenylethylamine 



HO 



-CH2-CHO 

 OH 

 homogentisic aldehyde 



HO 



/ VcHg-COOH 



OH 



homogentisic acid 



It has been shown that the amino-acid gives rise to homogentisic acid in the alcap- 

 tonuric subject (Neuberger, Rimington, and Wilson^"). In normal animals and human 

 subjects, both the amino-acid and the corresponding amine are fully metabolized 

 (Neuberger^; Leaf and Neuberger^^). This aspect of our findings has been more fully 

 discussed elsewhere (Blaschko et al}). 

 References p. 1361137. 



