Simultaneous Determination of the Rates of the TCA Cycle,Glucose Utilization,α-Ketoglutarate/Glutamate Exchange,and Glutamine Synthesis in Human Brain by NMR

¹³C isotopic tracer data previously obtained by ¹³C nuclear magnetic resonance in the human brain in vivo were analyzed using a mathematical model to determine metabolic rates in a region of the human neocortex. The tricarboxylic acid (TCA) cycle rate was 0.73 ± 0.19 μmol min⁻¹ g⁻¹ (mean ± SD; n = 4). The standard deviation reflects primarily intersubject variation, since individual uncertainties were low. The rate of α-ketoglutarate/glutamate exchange was 57 ± 26 μmol min⁻¹ g⁻¹ (n = 3), which is much greater than the TCA cycle rate; the high rate indicates that α-ketoglutarate and glutamate are in rapid exchange and can be treated as a single combined kinetic pool. The rate of synthesis of glutamine from glutamate was 0.47 μmol min⁻¹ g⁻¹ (n = 4), with 95% confidence limits of 0.139 and 3.094 μmol min⁻¹ g⁻¹; individual uncertainties were biased heavily toward high synthesis rates. From the TCA cycle rate the brain oxygen consumption was estimated to be 2.14 ± 0.48 μmol min⁻¹ g⁻¹ (5.07 ± 1.14 ml 100 g⁻¹ min⁻¹; n = 4), and the rate of brain glucose consumption was calculated to be 0.37 ± 0.08 μmol min⁻¹ g⁻¹ (n = 4). The sensitivity of the model to the assumptions made was evaluated, and the calculated values were found to be unchanged as long as the assumptions remained near reported physiological values.