Simultaneous in vivo monitoring of cerebral deoxyglucose and deoxyglucose-6-phosphate by 13C[1H] nuclear magnetic resonances spectroscopy.
The capacity of brain to dephosphorylate glucose-6-phosphate has been established, but the magnitude and significance of this capacity in vivo are debated, particularly in regard to dephosphorylation of the glucose analog 2-deoxyglucose. We now report results of external measurement in the brains of conscious rats with simultaneous resolution and quantification of both 2-deoxyglucose and its phosphorylated product by nuclear magnetic resonance (NMR) techniques that used 2-[6-13]deoxyglucose together with proton-decoupled 13C surface-coil spectroscopy. As NMR techniques require large doses of 2-deoxyglucose, a dose comparison was first made using decay curves of total label after tracer doses of 2-[14C]deoxyglucose without versus with unlabeled deoxyglucose at 500 mg/kg (the NMR dose). Similar cerebral half-lives for the two doses were found, and no behavioral evidence for toxicity of the NMR dose was seen. In vivo NMR monitoring of conscious rats showed that the analog reached maximal cerebral concentration within 10 min of the intravenous bolus and decayed with a half-life of 29 +/- 7 min (n = 4; mean +/- SEM), whereas 2-deoxyglucose-6-phosphate reached peak concentration between 30 and 40 min and decayed with a half-life of 2.1 +/- 0.3 h, equivalent to a fractional loss of 0.8%/min. Thirty-one percent (+/- 5%) of the total analog pool (which showed a half-life of 1.4 h) consisted of 2-deoxyglucose at 45 min after the bolus. The results support an active but limited role for dephosphorylation by normal brain in glucose analog (and potentially glucose) metabolism in the unstimulated conscious rat and a wide concentration range for the metabolic operations involved.
Kotyk
J J
JJ
Department of Chemistry, Washington University, St. Louis, Missouri.
Rust
R S
RS
Ackerman
J J
JJ
Deuel
R K
RK
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002247:Carbon Isotopes; D003837:Deoxy Sugars / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism*; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives*; D005958:Glucosephosphates / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014316:Tritium
D002247:Carbon Isotopes; D003837:Deoxy Sugars; D005958:Glucosephosphates; D014316:Tritium; C015785:2-deoxyglucose-6-phosphate; D019298:Glucose-6-Phosphate; D003847:Deoxyglucose