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 alternati ve substrates for energy during brain development; however, less is kn own about the use of these substrates by synaptic terminals. The prese nt 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-1 4]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 ma late were 8.55 +/- 0.78, 25.90 +/- 4.58, 42.28 +/- 3.54, 48.42 +/- 2.0 9, and 9.31 +/- 1.61 nmol/h/mg protein (mean +/- SEM), respectively, i n 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 t erminals isolated from 7- to 8-week-old rat brain. In competition stud ies using unlabelled added substrates, the addition of 3-hydroxybutyra te, lactate or glutamine greatly decreased the rate of (CO2)-C-14 prod uction from labelled glucose. Added unlabelled glucose increased the r ate of (CO2)-C-14 production from 3-hydroxybutyrate in synaptic termin als from 7- to 8-week-old rat brain, but had no effect on (CO2)-C-14 p roduction 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 a dded substrates altered the rate of (CO2)-C-14 production from labelle d glutamine or malate suggesting that these substrates are metabolized in relatively distinct compartments within synaptic terminals. Overal l the data demonstrate that synaptic terminals from both weanling and adult rat brain can utilize a variety of substrates for energy. In add ition, the competition studies demonstrate that the interactions of su bstrates change with age and suggest that there are multiple compartme nts of energy metabolism (or tricarboxylic acid cycle activity) in iso lated synaptic terminals.