GLUTAMIC ACID METABOLISM IN BRAIN AND LIVER 727 
study of metabolic rates. In experiments of longer duration the isotope concentration 
of liver aspartic acid equals, or is lower than that of glutamic acid. 
Without going into details of the calculation it is of some interest to obtain approxi- 
mate values for the half-lives of the different glutamic acids. This estimate can only 
be very approximate and give an indication of the range of values. 
On the basis of the isotope concentration in the free ammonia of the brain and 
in the a-amino group of glutamic acid, the bulk of glutamic acid has a half-life 
time of approx. 6h; on the other hand, the glutamic acid used for glutamine syn- 
thesis has a half-life time of less than 1 h. The pool size of this labeled glutamic acid 
would be approx. 15°% of the total. On the other hand, in liver the half-life time of 
TABLE IV 
LABELING OF GLUTAMIC ACID, GLUTAMINE AND ASPARTIC ACID 
AFTER INFUSION OF [4C|]NaHCO, 
Infusion: 0.11 mmole [14C]NaHCOsg, 0.65 mC in 25 min 


Counts/min]| umole 

Compound ——- = F 
Blood Brain cortex Liver 


Glutamine 390 500 1800 
Glutamic acid 260 360 2000 
Aspartic acid 420 1800 5300 

the total glutamic acid is close to that of the small pool of rapidly metabolized cerebral 
glutamic acid, around 30 min, the compartment of glutamic acid used for trans- 
amination in the synthesis of aspartic acid having a faster turnover. 
As pointed out before, the a-amino group of brain glutamine showed an !°N con- 
centration on the average ten times higher than that of glutamic acid, and in brain 
the amide group had the highest isotope concentration of all compounds analyzed. 
Glutamine was also the only compound which increased in brain. The question, 
therefore, arose as to the origin of the glutamic acid moiety of cerebral glutamine. A 
comparison of the isotope concentration in blood and brain glutamic acid and gluta- 
mine makes it unlikely that these blood constituents are the sources of the glutamic 
acid moiety of cerebral glutamine. Direct measurement of the uptake of labeled 
glutamic acid from the blood demonstrates that during the experimental period only 
a small fraction of glutamic acid could have come from the circulating blood. In 
order to maintain the tricarboxylic acid cycle if it should be depleted by a removal 
of ketoglutaric acid as glutamic acid for glutamine formation it would be necessary 
to replenish its intermediates by CO, fixation. Therefore, a study was made of the 
ability of brain tissue to fix COg, (ref. rr) a faculty which has been denied in varying 
degree by several authors. It can be seen that upon intracarotid administration of 
M4C|bicarbonate to cats, considerable radioactivity appears in cerebral aspartic and 
glutamic acids (Table IV). Aspartic acid has the highest specific activity, a finding 
which is in accord with the assumption that the fixation occurs on the oxaloacetate 
level. From a comparison of the specific activities of liver and brain aspartic acid, it 
References p. 730 
