Fig. 1. Glycogen turnover in resting brain.
The glycogen shunt involves passage of blood-borne glucose (Glc) through glycogen before the glucose-6-phosphate (Glc-6-P) is metabolized further via the glycolytic pathway to pyruvate (Pyr) or by the pentose phosphate shunt pathway (PPP). The PPP causes decarboxylation of carbon one of glucose and generates 2 NADPH per glucose for management of oxidative stress; the rest of the carbon re-enters the glycolytic pathway. Incorporation of label from blood-borne glucose into glycogen is low and mainly labels the outer tiers; the inner tiers are mainly unlabeled unless glycogen is depleted prior to labeling. Most of the label derived from glucose is recovered in the tricarboxylic acid (TCA) cycle-derived amino acids, mainly glutamate. However, lactate (Lac) is generated in neurons or astrocytes or both, and some is released from brain under resting conditions. Most of the glucose phosphorylated by hexokinase (HK) in brain (i.e., total glucose consumed) is oxidized, and the ratio of the rate of glucose to oxygen utilization (CMRO2/CMRglc) is close to the theoretical maximum of 6; measured values are slightly lower than 6 due to lactate efflux and non-oxidative biosynthetic activity.