CCXXXIII. METABOLISM OF a-KETOGLUTARIC ACID IN ANIMAL TISSUES

DEWAN [1938] and Adler et al. [1939] reported that certain enzyme preparations obtained from heart muscle bring about a reductive amination of ac-ketoglutaric acid. The hydrogen required in this reaction may be provided from other dehydrogenase systems via coenzyme I or II, especially from the ,-hydroxybutyric and i8ocitric dehydrogenases, according to the schemes: (1) ac-ketoglutaric acid+NH3+i8ocitric acid -+glutamic acid+ oxalosuccinic acid, or (2) oc-ketoglutaric acid + NH3 +,-hydroxybutyric acid glutamic acid + acetoacetic acid. We have studied the occurrence of these reactions (so far observed only in artificially combined enzyme systems) in surviving tissues. We find that a reductive amination of oc-ketoglutaric acid does in fact take place in kidney and heart muscle, but this reduction proves independent of the presence of isocitric or fl-hydroxybutyric acids. On the other hand it is found to be accompanied by a formation of succinic acid and C02, and the quantities of these substances formed show that the following reaction takes place: (3) 2oc-ketoglutaric acid +NH3=glutamic acid+ succinic acid+C02.