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 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.