Metabolites of 2-deoxyglucose in rat brain at 12-24 h: bounds on kinetic constants

Activities of 2-deoxy-D-glucose and its metabolites in rat brain were examined at 12, 16, 20, and 24 h after intraperitoneal injection of 14C-labeled 2-deoxy-D-glucose. Plasma radioactivity was monitored for 2 h before each of these determinations. As proportion of total brain radioactivity, 2-deoxy-D-glucose decreased monotonically from the unexpectedly high value of 22% at 12 h to 11% at 24 h after injection, 2-deoxy-D-glucose 6-phosphate decreased monotonically from 69% at 12 h to 23% at 24 h, and unphosphorylated products (of high and low molecular weight) increased from 10% at 12 h to 64% at 24 h. The data were analyzed in terms of a four-compartment model. Secure lower and upper bounds on the rate constant, k4*, for the dephosphorylation of 2-deoxy-D-glucose 6-phosphate were established: k4* was at least 0.0158 +/- 0.0014 . min-1 and at most 0.0385 +/- 0.0037 . min-1. If k4* is constant in time, then appreciable dephosphorylation occurs within the 45-min experimental period commonly used in the standard 2-deoxy-D-glucose method for estimating local cerebral glucose utilization. The possibility that the effective k4* is lower at such early times is reviewed in the light of a reanalysis of previously published data. Implications of these results for the 2-deoxy-D-glucose method are discussed from the points of view of numerical analysis and capillary heterogeneity.