Evidence for the cerebral uptake in vivo from two pools of glucose and the role of glucose-6-phosphatase in removing excess substrate from brain.
We propose the following scheme for cerebral uptake and overall metabolism of glucose in vivo: that brain selects from two pools of glucose anomers in arterial blood, that it takes up excess glucose, that glucose enters the brain tissue as glucose-6-phosphate through the actions of mutarotase and hexokinase, that some glucose-6-phosphate becomes metabolized to CO2 and some becomes incorporated into brain carbon pools, and that excess glucose-6-phosphate leaves brain through glucose-6-phosphatase and mutarotase activities. This results from our observations in arterio-venous studies for the determination of cerebral metabolism in humans in vivo that the cerebral uptake of [14C]glucose often appeared to differ from that of unlabeled glucose. With rapidly falling arterial radioactivity, unlabeled glucose uptake was more than [14C]glucose. With rising arterial radioactivity, [14C]glucose extraction exceeded unlabeled glucose. Studies with [14C]glucose-6-phosphate suggested that glucose-6-phosphatase in brain removes excess substrate by dephosphorylation. However, when arterial [14C]glucose increased slowly, [14C]glucose uptake varied considerably and the data resembled human cerebral metabolism of glucose anomers. An experiment employing [13C]glucose and NMR provided further support for our proposed scheme.
Sacks
W
W
Cowburn
D
D
Bigler
R E
RE
Sacks
S
S
Fleischer
A
A
D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002238:Carbohydrate Epimerases / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D005952:Glucose-6-Phosphatase / Q000378:metabolism*; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010766:Phosphorylation; D051381:Rats; D013057:Spectrum Analysis
D006593:Hexokinase; D005952:Glucose-6-Phosphatase; D002238:Carbohydrate Epimerases; C019646:aldose 1-epimerase; D005947:Glucose