ENERGY-METABOLISM IN CORTICAL SYNAPTIC TERMINALS FROM WEANLING AND MATURE RAT-BRAIN - EVIDENCE FOR MULTIPLE COMPARTMENTS OF TRICARBOXYLIC-ACID CYCLE ACTIVITY

It is well documented that the brain preferentially utilizes alternative substrates for energy during brain development; however, less is known about the use of these substrates by synaptic terminals. The present study compared the rates of (CO2)-C-14 production from 1 mM D-[6-C-14]glucose, L-[U-C-14]glutamine, D-3-hydroxy[3-C-14]butyrate, L-[U-C-14]lactate and L-[U-C-14]malate by synaptic terminals isolated from 17- to 18-day-old and 7- to 8-week-old rat brain. The rates of (CO2)-C-14 production from glucose, glutamine, 3-hydroxybutyrate, lactate and malate were 8.55 +/- 0.78, 25.90 +/- 4.58, 42.28 +/- 3.54, 48.42 +/- 2.09, and 9.31 +/- 1.61 nmol/h/mg protein (mean +/- SEM), respectively, in synaptic terminals isolated from 17- to 18-day-old rat brain and 12.95 +/- 1.64, 30.62 +/- 4.19, 16.09 +/- 2.62, 40.33 +/- 6.77, and 8.25 +/- 1.69 nmol/h/mg protein (mean +/- SEM), respectively, in synaptic terminals isolated from 7- to 8-week-old rat brain. In competition studies using unlabelled added substrates, the addition of 3-hydroxybutyrate, lactate or glutamine greatly decreased the rate of (CO2)-C-14 production from labelled glucose. Added unlabelled glucose increased the rate of (CO2)-C-14 production from 3-hydroxybutyrate in synaptic terminals from 7- to 8-week-old rat brain, but had no effect on (CO2)-C-14 production from any other substrates. Lactate also increased (CO2)-C-14 production from 3-hydroxybutyrate at 7-8 weeks, whereas the addition of 3-hydroxybutyrate decreased (CO2)-C-14 production from lactate only in synaptic terminals from 17- to 18-day-old rat brain. None of the added substrates altered the rate of (CO2)-C-14 production from labelled glutamine or malate suggesting that these substrates are metabolized in relatively distinct compartments within synaptic terminals. Overall the data demonstrate that synaptic terminals from both weanling and adult rat brain can utilize a variety of substrates for energy. In addition, the competition studies demonstrate that the interactions of substrates change with age and suggest that there are multiple compartments of energy metabolism (or tricarboxylic acid cycle activity) in isolated synaptic terminals.