Studies on brain metabolism

Abstract

The only amino-acid oxidized by brain is l( + ) glutamic acid which is oxidized to [alpha]-ketoglutaric acid and NH3 and further to H2O and CO2. [alpha]-Ketoglutaric acid was isolated as 2:4-dinitrophenyl-hydrazone, its further oxidation having been checked by arsenic. The enzyme responsible for the oxidation of l( + )-glutamic acid to [alpha]-ketoglutaric acid and NH3 does not attack d( [long dash] )-glutamic acid so long as it is bound in the cell or to some constituent of the cell (probably a lipoid). In solution however the specificity is changed and d( [long dash] )-glutamic acid alone is oxidised. The NH3 derived from the deamination of l( + )-glutamic acid disappears in secondary reactions leading to and beyond glutamine. The reaction l( + )-glutamic acid [forward arrow] [alpha]-ketoglutaric acid is reversible. The synthesis of glutamic acid from [alpha]-ketoglutaric acid is part of an NH3-binding mechanism which leads from glucose via pyruvic acid and [alpha]-ketoglutaric acid to glutamic acid and glutamine. [alpha]-Ketoglutaric acid is claimed to be an oxidation product of pyruvic acid, [alpha][alpha][image]- diketoadipic acid being an intermediate. The view is expressed that in vivo the glutamic acid deaminase is rather concerned with synthesis than with breakdown of glutamic acid.