GLUTAMIC ACID METABOLISM IN BRAIN AND LIVER 729 
of the pool, and its size. Tentative conclusions may also be drawn as to the localiza- 
tion of the cerebral metabolic compartments. The occurrence of glutamine synthe- 
tase in the microsomal fraction! led to the suggestion that the conversion of ad- 
ministered glutamic acid to glutamine occurs in the endoplasmic reticulum. On the 
other hand, the occurrence of this enzyme!, and in particular, of glutamic dehydro- 
genase in mitochondria! suggests that the conversion to the amide of glutamic acid 
synthesized in the cell occurs at mitochondrial sites (Fig. 3). In these instances we 
have been able to connect tentatively the compartmentalized metabolic event with 
definite cell structure. This may not always be possible or justified. In addition to 
these “visible” metabolic compartments, there may be compartments which are 

Fig. 3. Compartments of metabolism of administered glutamic acid and of glutamic acid syn- 
thesized in the tissue. The question marks indicate that the compartments of origin of GABA 
and glutathione are at present not determined with certainty. For abbreviations see p. 724. 
formed concomitant with metabolism and maintained by it. They may be called 
“invisible” compartments. 
It is clear that the control of intermediary metabolism and also the relation 
between function and metabolism cannot be interpreted rationally without a knowl- 
edge of the metabolic compartments. In the control and regulation of metabolism 
compartmentation of metabolic events and also the exchange between, and inter- 
dependence of, metabolic compartments will play a decisive role. This is apparent not 
only from the data presented here but also from the work of many other laboratories. 
It does not seem necessary to elaborate on the significance of metabolic compart- 
ments for an understanding of the relation between cerebral metabolism and function. 
Some time ago we studied the metabolic changes in experimental epileptogenic 
lesions which exhibit paroxysmal electric activity!®; the administration of small 
amounts of GABA eliminated the low frequency discharge. When the lesions are 
analyzed it was found that the glutamic acid, glutamine and glutathione concentra- 
tions have dropped to less than 50%, while the concentration of GABA had not 
changed. Upon systemic administration of GABA the low-frequency discharge was 
eliminated long before the GABA concentration rose’. These results show clearly 
that only a small fraction of GABA is affecting the properties of the lesion while the 
bulk of this compound is inert. 
The experiments with glutamic acid discussed here only serve as a model as to 
how the problem of the compartmentation of metabolic events may be attacked 
References p. 730 
