VOL. 4 (1950) SPECIFICITY OF DECARBOXYLASES I33 



III. 3:4-DIHYDROXYPHENYLSERINE (NORADRENALINE CARBOXYLIC ACID) 



The study of this compound has revealed another difference between the mamma- 

 Han and the bacterial decarboxylase^. On decarboxylation, it yields noradrenaline : 



KO HO 



HO<^ VCHOH-CHNH2-COOH " HO(^ V-CHOH-CH2NH2 + CO2 



3 : 4-dihydrox3rphenylserine noradrenaline 



It was found that the amino-acid was not decarboxylated by extracts of mammalian 

 tissues; it was, however, decarboxylated by the bacterial preparation. The rate of COg 

 formation with dihydroxyphenylserine was much slower than with tyrosine as substrate, 

 but the decarboxylation was almost quantitative ; approximately one-half of the racemic 

 substance was decarboxylated. The biological assay on the arterial blood pressure of 

 the spinal cat, together with the measurement of the amount of COg formed, showed that 

 the amine formed was laevo-noradrenaline. 



IV. N-METHYLATED AMINO-ACIDS 



Ten years ago, the observation was made that the introduction of a N-methyl group 

 abolished the substrate specifity for DOPA decarboxylase (Blaschko^^). Preparations 

 of mammalian liver and kidney which had DOPA decarboxylase activity were found 

 not to act on N-methyl-3 : 4-dihydroxyphenylalanine : 



HO 



HO / y CHOH-CHNH (CH3)-COOH 



This observation was made the basis of a scheme of biosynthesis of sympathin and 

 adrenaline. It had often been assumed previously that the formation of adrenaline 

 involved a decarboxylation reaction, but it was now shown that the body was not able 

 to produce a secondary amine by direct decarboxylation of the N-methyl-amino-acid, 

 whereas it was able to produce the corresponding primary amine. Primary amines with 

 sjmipathicomimetic activity were therefore postulated as intermediary products in 

 adrenaline synthesis. Earlier already, pharmacologists had discussed the possibility of 

 the identity of Cannon's "sympathin E" with noradrenaline (Bacq^^; Stehle and 

 Ellsworth^^). The biochemical findings gave a simple explanation for the occurrence 

 of this substance. 



Two amino-acids were studied in 1939: N-methyl-dihydroxyphenylalanine and 

 N-methyl-tyrosine. One important methylamino-acid, however, was not available at 

 that time ; this was N-methyl-3 : 4-dihydroxyphenylserine. Already in 1906, Friedmann^^ 

 had considered this acid as a possible precursor ot adrenaline ; he suggested that adren- 

 aline was formed in the reaction: 



HO HO 



Ho/ yCHOH-CHNH(CH3)-COOH ^ Ho/ yCHOH-CH2NH(CH8) -^ CO2 



N-methyl-3 : 4-dihydroxyphenylserine adrenaline 



(adrenaline carboxylic acid) 



This suggestion could not be tested by experiment until the synthesis of adrenaline 

 References p. 136113^. 



