Localized 13C NMR spectroscopy in the human brain of amino acid labeling from D-[1-13C]glucose.
Cerebral metabolism of D[1-13C]glucose was studied with localized 13C NMR spectroscopy during intravenous infusion of enriched [1-13C]glucose in four healthy subjects. The use of three-dimensional localization resulted in the complete elimination of triacylglycerol resonance that originated in scalp and subcutaneous fat. The sensitivity and resolution 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. [4-13C]Glutamate labeled rapidly reaching close to maximum labeling at 60 min. The label flow into [3-13C]glutamate clearly lagged behind that of [4-13C]-glutamate and peaked at t = 110-140 min. Multiplets due to homonuclear 13C-13C coupling between the C3 and C4 peaks of the glutamate molecule were observed in vivo. Isotopomer analysis of spectra acquired between 120 and 180 min yielded a 13C isotopic fraction at 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 [4-13C]glutamate was directly quantified to be 2.4 +/- 0.1 mumol/ml-brain. Together with the isotopomer data this gave a calculated brain glutamate concentration of 9.1 +/- 0.7 mumol/ml, which agrees with previous estimates of total brain glutamate concentrations. The agreement suggests that essentially all of the brain glutamate is derived from glucose in health human brain.
Gruetter
R
R
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06510.
Novotny
E J
EJ
Boulware
S D
SD
Mason
G F
GF
Rothman
D L
DL
Shulman
G I
GI
Prichard
J W
JW
Shulman
R G
RG
D000328:Adult; D000596:Amino Acids / Q000096:biosynthesis*; D001224:Aspartic Acid / Q000096:biosynthesis; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002247:Carbon Isotopes; D005260:Female; D005947:Glucose / Q000378:metabolism*; D018698:Glutamic Acid / Q000096:biosynthesis; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D012016:Reference Values; D013997:Time Factors
D000596:Amino Acids; D001786:Blood Glucose; D002247:Carbon Isotopes; D001224:Aspartic Acid; D018698:Glutamic Acid; D005947:Glucose