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

Abstract

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.