546 G. GUROFF AND S. UDENFRIEND 
In previous work from this laboratory! L-tyrosine (400 mg/kg) was injected into 
fasted, 250 g rats and the plasma- and brain-tyrosine levels observed. It can be seen 
(Fig. 1) that the plasma-tyrosine !evel rose rapidly and remained relatively constant 
over the 2-h experimental period. The brain-tyrosine level rose more slowly but 
after 60 min equaled and exceeded the plasma level. The brain-to-plasma ratio 
CBI 
BRAIN-TO-PLASMA RATIOS OF L- AND D-TYROSINE FOLLOWING 
INTRAPERITONEAL ADMINISTRATION 



Time L-Tyrosine* p-T yrosine* 
(min) (400 mg/kg) (4oo mg/kg) 
15 0.32 0.09 
30 0.63 0.12 
60 0.95 0.2 
120 1.32 0.52 

* Endogenous t-tyrosine subtracted from total tyrosine of 
brain and plasma. 
during the experiment (Table 1) clearly showed this relationship. In the fasting 
animal the endogenous tyrosine ratio was 1.3-1.4. When equilibrium was reesta- 
blished after approx. go min this ratio was again reached even though the absolute 
values were about 5-fold higher. To allow comparisons between the L- and D-isomers 
the endogenous tyrosine levels have been subtracted in both cases. The uptake of 
b-tyrosine (Table I) was much slower under similar conditions. It has been shown, 
however!’, that little or no racemization of the injected bD-tyrosine occurred over the 
time period of these experiments and that, in fact, the increased tyrosine in the 
brain was the D-isomer. 
The presence of certain other amino acids in the blood had a marked effect on 
the uptake of tyrosine by brain (Table II). The prior injection of aromatics such 
as tryptophane, or of aliphatics such as isoleucine or leucine, inhibited tyrosine 
uptake. On the other hand, molecules such as glutamate, arginine, or threonine had 
little or no effect. Also, certain unnatural amino acids, such as p-fluoro-pL-phenyl- 
alanine or norleucine!’, inhibited tyrosine uptake. The acid analogs, #-hydroxy- 
phenylacetic acid and isovaleric acid!® did not inhibit tyrosine uptake. In addition, 
the earlier suggestion that D-tyrosine was an inhibitor of L-tyrosine uptake has been 
examined and has not been substantiated. The effective inhibitors act only during the 
first approx. 30 min of these experiments, probably because they do not remain in 
the blood stream as long as does tyrosine. 
Structural alterations changed the uptake of molecules of this type (Fig. 2). It 
can be seen that tyramine and a-methyl-pr-tyrosine also entered brain but that p- 
hydroxyphenylacetic acid did not. The figures in parentheses indicate the brain-to- 
plasma ratio of each compound 30 min after administration. Other tyrosine analogs 
with additional carboxyls added to the ring structure did not enter brain to any 
significant extent. 
References p. 553 
