LOCALIZED C-13 NMR-SPECTROSCOPY IN THE HUMAN BRAIN OF AMINO-ACID LABELING FROM D-[1-C-13]GLUCOSE

Cerebral metabolism of D[1-C-13]glucose was studied with localized C-1 3 NMR spectroscopy during intravenous infusion of enriched [1-C-13]glu cose in four healthy subjects. The use of three-dimensional localizati on resulted in the complete elimination of triacylglycerol resonance t hat originated in scalp and subcutaneous fat. The sensitivity and reso lution were sufficient to allow 4 min of time-resolved observation of label incorporation into the C3 and C4 resonances of glutamate and C4 of glutamine, as well as C3 of aspartate with lower time resolution. [ 4-C-13]Glutamate labeled rapidly reaching close to maximum labeling at 60 min. The label flow into [3-C-13]glutamate clearly lagged behind t hat of [4-C-13]glutamate and peaked at t = 110-140 min. Multiplets due to homonuclear C-13-C-13 coupling between the C3 and C4 peaks of the glutamate molecule were observed in vivo. Isotopomer analysis of spect ra acquired between 120 and 180 min yielded a C-13 isotopic fraction a t C4 glutamate of 27 +/- 2% (n = 4), which was slightly less than one- half the enrichment of the C1 position of plasma glucose (63 +/- 1%), p < 0.05. By comparison with an external standard the total amount of [4-C-13]glutamate was directly quantified to be 2.4 +/- 0.1 mu mol/ml- brain. Together with the isotopomer data this gave a calculated brain glutamate concentration of 9.1 +/- 0.7 mu mol/ml, which agrees with pr evious estimates of total brain glutamate concentrations. The agreemen t suggests that essentially all of the brain glutamate is derived from glucose in healthy human brain.