562 A. LAJTHA 
that one L-amino acid leaves the brain by being exchanged for another though no 
indication for this possibility was found in the present experiments by measuring 
total amino nitrogen in the extracts). It follows then, that if the relative rates of the 
outflow of the two forms could be compared the differences would be greater than 
shown in Table V. The relationship of this unidirectional flow to exchange is not 
clear at the present time, but the possibility exists that they refer to the same 
mechanism??; 3°. 
Although two isomers of any particular amino acid may be transported by the 
same mechanism, considerable experimental evidence makes it likely that all the 
amino acids are not transported through the same mechanism. Some specificity in 
the effects of increased cerebral levels on exchange rates (Tables I and II) have been 
discussed already. The fact that 77 vivo tyrosine transport was inhibited by some but 
not all amino acids was also interpreted as evidence of more than one amino acid 
transport mechanism**. Only a little competition could be found among amino acids 
studied in a comparison of individual with simultaneous cerebral entrance and exit®?. 
A transport system specific for L- and D-tryptophan was found in E. col". 
These findings show the specificity of the transport processes with the possibility 
of individual control of the passage of a specific metabolite. It is likely that a separate 
carrier exists for each amino acid or group of amino acids in the brain. 
In an investigation of stereospecificity it is important to distinguish between the 
rate of uptake and the levels reached at equilibrium. It was found in our laboratory? 
that D-leucine or p-phenylalanine penetrated the brain from the plasma or from the 
CSF at a lower rate than the corresponding L-form, but that at equilibrium the level 
of p-leucine was higher, and the level of D-phenylalanine lower, than that of the cor- 
responding L-form, showing that the rate of passage is not the only factor determining 
the final equilibrium. 
CONCLUSION 
With our increasing knowledge of amino acid transport in simpler systems it becomes 
possible to investigate the systems operative in such a complex organ as the brain. 
Although this organ has certain advantages for a study of transport processes, the 
picture is far from simple. Questions such as the mechanism of transport, the relation- 
ship of exchange, influx and efflux, the metabolic control of transport, and differences 
between cerebral transport mechanisms as opposed to other organs cannot be 
answered at the present time. 
The evidence gained in the investigation of the passage of amino acids in the brain 
shows that at least in part this passage is carrier mediated and that it has an active, 
energy-requiring component. Quantitative and qualitative differences in passage of 
the various compounds were demonstrated; metabolite specificity as well as stereo- 
specificity and homeostatic control reaching down to separate brain areas were found. 
The transport processes are two directional, are mediated in efflux as well as in influx, 
and show changes with development. 
A closer understanding of cerebral transport mechanisms is essential, since it seems 
likely that they have significant influence on brain metabolism. 
References p. 563 
