Metabolic Modeling of Acetate Transport and Metabolism in the Rat Brain

Abstract

The aims of this study were first to determine kinetic parameters for acetate transport and utilization in the brain and then use this information to perform 13C dynamic modeling in order to determine absolute cerebral metabolic fluxes.Previously measured in vivo 13C time courses obtained during infusion of [2‐13C] acetate in rat brain under morphine anesthetic at 9.4 T [1] were used for the modeling.Fitted values for transport and uptake kinetics were: Vtrmax= 0.96 ± 0.18 μmol/g/min and KtrM= 4.2 ± 0.8 mM for acetate transport through the BBB and Vutmax=0.50 ± 0.08 μmol/g/min with KMut= 0.01 ± 0.14 mM for acetate utilization through the mitochondrial inner membrane and acetyl‐CoA synthetase from acetate. The steady‐state cerebral metabolic flux of acetate (CMRace) was 0.49 ± 0.08 μmol/g/min (mean ± SD; n = 4).Metabolic fluxes determined from modeling of the 13C time courses were: VTCA(n)= 1.8 μmol/g/min, VTCA(g)= 0.27 μmol/g/min, VPC= 0.1 μmol/g/min, VX=1.4 μmol/g/min and VNT= 0.23 μmol/g/min.Maximum transport capacity of acetate through the BBB was two‐hold higher than the maximum rate of brain acetate utilization and KtrM was much higher than KMut, implying that the rate‐limiting step for acetate metabolism occurs after acetate enters the brain.[1] Deelchand et al. ISMRM 2006This work was supported by NIH P41 RR008079, P30 NS057091 and R01 NS038672