Studies on brain metabolism

Abstract

The anaerobic metabolism of pyruvic and [alpha]-ketoglutaric acids in sliced and minced brain has been studied. The relation, pyruvic acid disappearance:lactic acid formation:CO2 evolution = 2:1:1 in both slices and mince, indicating a dismutation of pyruvic acid. With brain slices about 80% of the theoretical amt. of acetic acid is found. The remaining 20% is accounted for by succinic acid. With minced brain only about 10% of the theoretical amount of acetic acid is found; the yield of succinic acid is increased and accounts for about 60% of the oxidized pyruvic acid. The deficit of 30% is not accounted for by [beta]-hydroxybutyric acid. The relation, keto-glutaric acid disappearance:succinic acid formation:hydroxy-glutaric acid formation :CO2 evolution = 2:l :1:1, in both slices and mince, indicating a dismutation of ketoglutaric acid. The evidence for the formation of l([long dash])[alpha]-hydroxy-glutaric acid consists (a) in the formation of a substance which is oxidized by an enzyme extract under conditions characteristic for l([long dash])[alpha]-hydroxyglutaric acid, (b) in the formation of a substance the optical properties of which agree with those of l([long dash])[alpha]-hydroxyglutaric acid, (c) in the isolation of Zn hydroxyglutarate. The anaerobic decarboxy-lation of [alpha]-keto-acids is accelerated by the addition of brilliant cresyl blue. The relation of dye reduced :CO2 evolved = 2:1, if the CO2 evolution in absence of the dye is not subtracted.[long dash]It is concluded that the decarboxylation of a-keto-acids is an oxidative process; the conversion of pyruvic acid into succinic acid is brought about by an oxidative condensation of 2 mol. of nascent acetic acid; the H acceptor for this reaction is not pyruvic acid and is probably available in small amts. in the slice and liberated upon destruction of the cell; [alpha]-ketoglutaric acid is probably not an intermediate in this reaction; and dismutations of [alpha]-keto-acids occur only under strictly anaerobic conditions, and are replaced by dehydrogenations in presence of O or of a dye.