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

SIMULTANEOUS DETERMINATION OF THE RATES OF THE TCA CYCLE, GLUCOSE-UTILIZATION, ALPHA-KETOGLUTARATE GLUTAMATE EXCHANGE, AND GLUTAMINE SYNTHESIS IN HUMAN BRAIN BY NMR
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DOI:
10.1038/jcbfm.1995.2
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发表时间:
1995-01-01
影响因子:
6.3
通讯作者:
NOVOTNY, EJ
NOVOTNY, EJ
中科院分区:
医学1区
文献类型:
--
作者:
MASON, GF;GRUETTER, R;NOVOTNY, EJ

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使用数学模型分析先前通过C-13核磁共振在体内人脑中获得的C-13同位素示踪剂数据,以确定人类新皮层区域中的代谢率。三羧酸(TCA)循环速率为0.73 +/- 0.19 μ mol min(-1)g(-1)(平均值+/- SD; n = 4)。标准差主要反映了受试者间的变异,因为个体不确定性较低。α-酮戊二酸/谷氨酸的交换速率为57 +/- 26 μ mol min(-1)g(-1)(n = 3),远大于TCA循环速率;高速率表明α-酮戊二酸和谷氨酸快速交换,可视为单一的联合动力学差。谷氨酸合成谷氨酰胺的速率为0.47 μ mol min(-1)g(-1)(n = 4),95%置信限为0.139和3.094 μ mol min(-1)g(-1);个体不确定性严重偏向高合成速率。根据TCA循环速率,脑耗氧量估计为2.14 +/- 0.48 μ mol min(-1)g(-1)(5.07 +/- 1.14 ml 100 g(-1)min(-1); n = 4),脑葡萄糖消耗速率计算为0.37 +/- 0.08 μ mol min(-1)g(-1)(n = 4)。评价了模型对假设的敏感性,发现只要假设保持接近报告的生理值,计算值就保持不变。
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.