TYROSINE METABOLISM 



307 



to reduce the tissue tyramine concentration. Mardashev and Semina 

 (1961) found that the tyrosine decarboxylase from Streptococcus fecalis is 

 inhibited 20% by 8.3 mM cysteine and 25% by 8.3 mM homocysteine 

 when substrate concentration is 2.8 mM. This is a general phenomenon seen 

 with several amino acid decarboxylases and is presumably due to the for- 

 mation of complexes of the inhibiting amino acids with pyridoxal phosphate. 

 The tyrosine-activating enzyme of pig pancreas catalyzes the first 



Amino acid + ATP + E -> E-amino acyl-AMP + PP 



step in the incorporation of amino acids into proteins. This also would 

 be a very interesting step to investigate from the standpoint of analog 

 inhibition, but our present information is meager. Schweet and Allen 

 (1958) found that 3-fluoro-lL-tyrosine activated 50% the rate of L-ty- 

 rosine and does not inhibit. L-tyrosinamide inhibits weakly but tyramine 

 inhibits the phosphate exchange reaction 80% at 0.2 mM, this inhibition 

 being reduced by increase in substrate concentration. The importance of 

 the p-hydroxyl group is indicated by the fact that no inhibition is seen 

 with phenylethylamine. 



Dihydroxyphenylalanine (Dopa) Decarboxylase 



This enzyme is on the pathway leading from tyrosine to the important 

 catecholamines, epinephrine and norepinephrine, and lately has been the 

 subject of much investigation because of the possible clinical applications 

 of producing a selective block at this step. Inhibitors have indeed been 

 found which are effective in vivo, reduce amine formation, and lower the 

 blood pressure. The sequence of reactions for the formation of amines 

 from dopa is the following: 



HO 



HO 



NH3 

 -CH— COO' 



dopa 



decarboxylase 



HO 



CH^ CH,— NH, 



Dopa 



Dopamine 



dopamine /3-oxidase 



OH 



1 H 



CH— CH,— NH, 



Epinephrine 



