GLUTAMIC ACID METABOLISM IN BRAIN AND LIVER F25 
of the metabolically active glutamic acid? Since we have administered the labeled 
glutamic acid intracisternally we cannot exclude with certainty that this conversion 
proceeds in the cerebral surface membranes or the ependymal linings. We have 
no decisive evidence against such an assumption, but it is significant in this connec- 
tion that only 2 min after the administration of labeled aspartic acid the isolated 
brain glutamine has five times the specific activity of brain glutamic acid®. One would 
have to assume that the whole chain of events leading from aspartic to ketoglutaric 
acid, glutamic acid and glutamine would essentially occur outside the brain tissue. 
Similarly, some time ago ROBERTS® mentioned the results of experiments in which, 
after the intracisternal administration of {4#C\|GABA, glutamine showed a higher 
activity than glutamic acid. Since glutamine synthetase occurs in high concentra- 
tions in the microsomes! it was suggested that the administered glutamic acid is 

Fig. 1. Pools of administered glutamic acid (measured by glutamine synthesis). 
For abbreviations see p. 724. 
converted into glutamine in the endoplasmic reticulum before it mixes with the 
total tissue content. A very approximate estimate of the size of the active glutamic 
acid compartment may be of interest. With a ratio of 5 : 1 of the specific activity of 
glutamine to that of glutamic acid, the glutamic acid compartment cannot be larger 
than 20%, of the tissue glutamic acid. 
Because of the uncertainty of the site of conversion of administered glutamic acid 
to glutamine the metabolism of glutamic acid synthesized in the brain and liver was 
studied. In collaboration with BERL, TAKAGAKI, CLARKE AND PuRPURA’, ®9NH, was 
administered to cats by intracarotid infusion and the various members of the glutamic 
acid family isolated. 1 mmole of ammonium acetate was infused per minute and the 
animal exsanguinated at the end of the period of infusion. There are several obser- 
vations which should be stressed (Table III). Upon infusion of ammonia all con- 
stituents analyzed stayed constant with the exception of cerebral glutamine, the 
concentration of which rose by at least 50°. This finding, in accord with results 
from other laboratories’, shows that in the brain glutamine formation is the major 
removal mechanism for ammonia. Pertinent to our discussion is the observation that 
the N concentration of the a-amino group of glutamine was about ten times higher 
than that of the a-amino group of glutamic acid. If we do not assume a still undis- 
covered pathway for the synthesis of glutamine, we have to conclude that this glu- 
tamine is synthesized from newly made glutamic acid before the acid has time to 
mix with the total tissue glutamic acid. What has already been demonstrated for 
References p. 730 
