Development of mitochondrial energy metabolism in rat brain

Abstract

The development of pyruvate dehydrogenase and citrate synthase activity in rat brain mitochondria was studied. Whereas the citrate synthase activity started to increase at about 8 days after birth, that of pyruvate dehydrogenase started to increase at about 15 days. Measurements of the active proportion of pyruvate dehydrogenase during development were also made. The ability of rat brain mitochondria to oxidize pyruvate followed a similar developmental pattern to that of the pyruvate dehydrogenase. The ability to oxidize 3-hydroxybutyrate showed a different developmental pattern (maximal at 20 days and declining by half in the adult), which was compatible with the developmental pattern of the ketone-body-utilizing enzymes. The developmental pattern of both the soluble and the mitochondrially bound hexokinase of rat brain was studied. The total brain hexokinase activity increased markedly at about 15 days, which was mainly due to an increase in activity of the mitochondrially bound form, and reached the adult situation (approximately 70% being mitochondrial) at about 30 days after birth. The release of the mitochondrially bound hexokinase under different conditions by G-6-P was studied. There was insignificant release of the bound hexokinase in media containing high KCl concentrations by G-6-P, but in sucrose media half-maximal release of hexokinase was achieved by 70 .mu.M G-6-P. The production of G-6-P by brain mitochondria in the presence of Mg2+ and glucose was demonstrated, together with the inhibition of this by atractyloside. The possible biological significance of the similar developmental patterns of pyruvate dehydrogenase and the mitochondrially bound kinases, particularly hexokinase, in the brain was discussed. This association may be a mechanism for maintaining an efficient and active aerobic glycolysis which is necessary for full neural expression.