724, H. WAELSCH 
tamine may be synthesized in the mammalian body. If {14C|glutamic acid is administer- 
ed to animals in order to study glutamine synthesis, the administered glutamic acid will 
first, if we deal with a homogeneous system, be diluted by the tissue glutamic acid, 
before the conversion to glutamine, the labeled glutamine again being diluted by 
the unlabeled tissue glutamine. Therefore, in a homogeneous system the glutamine 
will have not more than the specific activity of the glutamic acid but probably less, 
since not all of the glutamine will, in the experimental period, be derived from the 
labeled glutamic acid. 




TABLE II 
CEREBRAL METABOLISM OF INTRACISTERNALLY ADMINISTERED ['C]GLUTAMIC ACID 
(RATS) 
Specific activity Total counts in 
Time a counts/uM/min I g fresh brain 
: Subs 2 oe 5 
(min) BES Gte ————— —= — (Glutamic + 
Plasma Brain Liver glutamine) 
Mle Glutamic 7 700 
92 000 
Glutamine 3 300 
I Glutamic 180 000 5 500 200 
: 92 000 
Glutamine I 200 7 300 66 
2 Glutamic 130 000 3, 200 800 
: 92 000 
Glutamine 2 200 12 000 600 
5 Glutamic 34 000 2 700 770 
; J f 97 000 
Glutamine 6 100 14 000 760 
15 Glutamic 8 900 2 200 190 pe 
Glutamine 6 500 II 000 280 gs 
30 Glutamic 3, 300 2 100 180 - 
; = 58 000 
Glutamine 870 7 300 240 

Let us compare this prediction with the actual data. The experiments were carried 
out in collaboration with Bert and Lajyrua®, 4: 6, [!4C|glutamic acid was injected 
intracisternally into rats, and the animals were decapitated 15 sec-60 min after 
the administration of the labeled amino acid (Table Il). Only the experiment of 
15 sec duration shows the expected relationship, glutamic acid having a higher 
specific activity than the amide. In all other experiments, glutamine has a higher 
specific activity than its precursor amino acid, glutamic acid, up to five times in the 
15-min experiment. That this is not due to dilution by cold glutamic acid fed into 
the system or other metabolic reactions may be seen from the fact that during the 
first 15 min the sum of counts of glutamic acid and glutamine stays constant per g 
of brain. Neither GABA nor glutathione ever reaches the specific activity of glutamic 
acid when this acid is administered as the labeled compound. On the basis of the 
glutamic acid-glutamine data it may be concluded that the administered glutamic 
acid is converted into glutamine before it is mixed with the whole tissue glutamic 
acid, z.e. only a small fraction of the glutamic acid takes part in this conversion 
while most of the tissue glutamic acid is inert (Fig. 1).* Where is this compartment 
* In this and also in Figs. 2 and 3 “inert” glutamic acid, glutamine or aspartic acid refers to 
the large tissue compartment of the respective compound with a rate of turnover which is lower 
than, or relatively inert, when compared with the small compartment of high metabolic activity. 
Abbreviations: GA: Glutamic acid; GLINE: glutamine; ASP: aspartic acid; GSH: gluta- 
thione; MT: mitochondria; EPR: endoplasmic reticulum. 
References p. 730 
