134 H. BLASCHKO VOL. 4 (1950) 



carboxylic acid was achieved by Dalgliesh and Mann^^. We have recently examined 

 this compound. It was found not to be decarboxylated by a number of mammahan 

 tissue extracts and, unhke the corresponding amino-acid, dihydroxyphenylserine, it was 

 not a substrate of the bacterial enzyme preparation. 



The substrate specificity of DOPA decarboxylase in connexion with pathways of 

 adrenaline synthesis has recently been reviewed elsewhere (Blaschko^''). Two possible 

 ultimate precursors of adrenaline were discussed: noradrenaline and N-methyl-3 : 4- 

 dihydroxyphenylethylamine (also known as epinine) : 



HO HO 



lio( V-CHOH-CHjNHg Ho/^^VcHa-CHj-NHiCHg) 



noradrenaline epinine 



The role of epinine in the biosynthesis of adrenaline has recently been discussed 

 by Danneel^^ and by Holtz and Kroneberg^^. The presence of this substance in 

 mammalian tissue has never been demonstrated. Recently, noradrenaline has been 

 found in human tumours of the suprarenal medulla (Holton^") as well as in the supra- 

 renal gland (Schumann^^). Evidence is also accumulating that both adrenaline and 

 noradrenaline are released from the suprarenal medulla (Meier and Bein^^; Bulbring. 

 and Burn-^; Holtz and Schumann^*). 



v. DOPA decarboxylase AND PYRIDOXINE DEFICIENCY 



Like the mammalian enzyme, the bacterial enzyme does not act on N-methyl- 

 tyrosine (Epps'^) and N-methyl-dihydroxyphenylserine. This suggests that the inability 

 to act on N-methyl-amino-acids is due to a property common to both enzymes. 



It is known that the bacterial codecarboxylase (Gale and Epps^^), the prosthetic 

 group of the bacterial tyrosine decarboxylase, is pyridoxal phosphate (Gunsalus, 

 Bellamy and Umbreit^^). Green, Leloir, and Nocito" achieved a partial purification 

 of DOPA decarboxylase and a reactivation of the apoenzyme by pyridoxal phosphate. 

 It is, however, not generally accepted that DOPA decarboxylase contains pyridoxal 

 phosphate (see Martin and Beiler^^; Work and Work-^). 



When the DOPA decarboxylase activity was determined in liver extracts of rats 

 reared on a diet deficient in pyridoxine (vitamine Bg), enzymic activity was found to be 

 low, and in a few of the extracts the activity had practically disappeared (Blaschko, 

 Carter, O'Brien, and Sloane Stanley^"; and unpublished observations). Addition 

 of pyridoxal plus ATP in vitro brought about a partial restoration of the enzymic 

 activity. More recently, through the kindness of Dr K. Folkers, we have been able to 

 test the effect of synthetic codecarboxylase: we have found that it is possible to restore 

 the activity of the extracts from Bg-deficient animals to normal values by the addition 

 in vitro of 10 /<g of synthetic codecarboxylase to the equivalent of 550 mg of fresh weight 

 of liver. These experiments allow us to conclude that DOPA decarboxylase, like the 

 bacterial tyrosine decarboxylase, contains pyridoxal phosphate. 



There is experimental support for a suggestion by Snell^^ that in transamination 

 the initial reaction between amino-acid and pyridoxal phosphate involves the formation 

 of a -N = C( bond. In analogy, it seems likely that the decarboxylation requires a 

 reaction between the amino group of the amino-acid and the aldehyde group of pyridoxal 

 phosphate : 

 References p. 136J13J. 



