SIMULTANEOUS DETERMINATION OF THE RATES OF THE TCA CYCLE, GLUCOSE-UTILIZATION, ALPHA-KETOGLUTARATE GLUTAMATE EXCHANGE, AND GLUTAMINE SYNTHESIS IN HUMAN BRAIN BY NMR

C-13 isotopic tracer data previously obtained by C-13 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 mu mol min(-1) g(-1) (mean +/- SD; n = 4). The standard deviation reflects primarily intersubject variation, since individual uncertainties were low. The rate of alpha-ketoglutarate/glutamate exchange was 57 +/- 26 mu mol min(-1) g(-1) (n = 3), which is much greater than the TCA cycle rate; the high rate indicates that alpha-ketoglutarate and glutamate are in rapid exchange and can be treated as a single combined kinetic poor. The rate of synthesis of glutamine from glutamate was 0.47 mu mol min(-1) g(-1) (n = 4), with 95% confidence limits of 0.139 and 3.094 mu mol 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 mu mol 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 mu mol 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.