Metabolic Fluxes Between [14C]2‐Deoxy‐D‐Glucose and [14C]2‐Deoxy‐D‐Glucose‐6‐Phosphate in Brain In Vivo

Abstract

The rates of the phosphorylation and dephosphorylation of 2-deoxyglucose were measured in rat brain in vivo using tracer kinetic techniques. The rate constant for each reaction was estimated from 2 separate experiments with different protocols for tracer administration. Tracer amounts of [1-14C]2-deoxyglucose (1 .mu.Ci) were injected through the internal carotid artery (intraarterial experiment), or through the atrium (i.v.experiment). Brains were sampled by freeze-blowing at various times after the injection. In the intraarterial experiment, the rate constant for the forward reaction from 2-deoxyglucose to 2-deoxyglucose phosphate was calculated by dividing the initial rate of 2-deoxyglucose phosphate production by the 2-deoxyglucose content in brain. The rate constant for the reverse reaction from 2-deoxyglucose was calculated from the decay constant of 2-deoxyglucose phosphate. The rate constants estimated were 10.1 .+-. 1.4%/min (SD) and 3.00 .+-. 0.01%/min (SD), respectively, for the forward and reverse reactions. In the i.v. experiment, rate constants for both reactions were estimated by compartmental analysis. By fitting data to program SAAM-27, the rate constants for the forward and reverse reactions were estimated as 11.4 .+-. 0.4%/min (SD) and 5.1 .+-. 0.4%/min (SD), respectively. The rate constants determined were compared to those for the reactions between glucose and G-6-P, estimated previously from labeled glucoses. The rate of glucose utilization measured by the 2-deoxyglucose method reflects the rate of the hexokinase reaction and not the rate of glucose utilization or brain energy utilization.