PART III 

 DRUG ACTION 



SUBSTRATE SPECIFICITY OF AMINO-ACID DECARBOXYLASES 



by 



H. BLASCHKO 

 Department of Pharmacology, University of Oxford {England) 



During the last two years a number of observations on substrates of amino-acid 

 decarboxylases have been recorded from this laboratory. In this review the attempt is 

 made to correlate the results obtained and to arrive at conclusions of a more general 

 character. The experimental data and the methods used have been described elsewhere 

 (Blaschko, Holton, and Sloane Stanley^' 2- Blaschko^; Sloane Stanley^* s). 



The decarboxylation of L-3 : 4- dihydroxyphenylalanine (DOPA) is catalysed by 

 two enzymes: the mammahan L-DOPA-decarboxylase (Holtz, Heise, and Ludtke^) 

 :ind the bacterial L-tyrosine decarboxylase (Epps'). The two enzymes differ in their 

 affinity for L-tyrosine: this is probably the "natural" substrate of the bacterial enzyme, 

 but it is not attacked by the mammalian enzyme. The difference in substrate specificity 

 of the two enzymes has been studied more systematically. 



The experimental procedure adopted is easily described. As a source of the bacterial 

 enzyme we used an acetone-dried preparation of Streptococcus f^ecalis R (ATCC 4083) ; 

 we owe this strain to Professor I. C. Gunsalus. The bacteria were usualty grown in a 

 medium free of vitamin Bgi in these preparations the tyrosine apodecarboxylase was 

 present, but had to be completed by the addition in vitro of pyridoxal and ATP. In 

 some of the experiments we used a "complete" preparation obtained from cells grown 

 in the presence of pyridoxal. As a source of the mammalian DOPA decarboxylase we 

 used fresh tissue extracts, from guinea-pigs kidney or from rats liver. 



The enzymic decarboxylation of each amino-acid was measured by following the 

 time course of CO2 formation manometrically. If an amino-acid was found to be decarbo- 

 xylated, the contents of the manometer flasks were used for a determination of the 

 pharmacological activity of the amine formed. The activity was tested on the arterial 

 blood pressure of the spinal cat; the pressor activity of the amine formed by enzjmae 

 action was compared with that of the synthetic amine. 



I. monohydroxyphenylalanines 



Our results are summarized on Table I. It was found that m-hydroxyphenylalanine 

 (the "meta-tyrosine" of Blum^) was a substrate of the mammalian enzyme; the rate of 

 decarboxylation was slightly less than with 3:4-dihydroxyphenylalanine as substrate. 

 The bacterial preparation also acted on w-hydroxyphenylalanine, at about one-third 

 of the rate of decarboxylation of tyrosine. 



In the mammalian tissue extracts, o-hydroxyphenylalanine (Blum's® "oitho- 

 tyrosine") was decarboxylated at approximately the same rate as the meta hydroxy 

 References p. 136I137. 130 



