308 



2. ANALOGS OF ENZYME REACTION COMPONENTS 



A block of dopa decarboxylase would thus decrease the rate of formation 

 of these three physiologically active amines in the tissues. 



Of historical interest are the following observations on the analog inhi- 

 bition of this enzyme: dopamine (Blaschko, 1942), epinephrine (Schapira, 

 1946), various aromatic amines (tryptamine, tyramine, phenylethylamine, 

 etc.) (Polonovski et al., 1946), and the various hydroxy, methoxy, and 

 dimethoxy derivatives of phenylethylamine, the dimethoxy analogs being 

 the most potent (Gonnard, 1950). 



These studies were extended in important ways by Sourkes (1954), 

 who discovered the potent inhibiting activity of certain a-methylphenyl- 

 alanines (Table 2-10). Especially inhibitory is a-methyldopa and this sub- 



Table 2-10 

 Inhibition of Dopa Decarboxylase from Pig Kidney Cortex " 



" Concentration of DL-dopa 4 mM, pH 6.8, preincubation with inhibitor 15 min. 

 PA — phenylalanine, and dopa = 3,4-dihydroxyphenylalanine. Relative binding ener- 

 gies calculated on the basis of competitive inhibition, which may not be strictly true; 

 in any event, these values give a better indication of the relative inhibitory potency 

 than the per cent inhibition at different concentrations. (Data from Sourkes, 1954.) 



