Metabolic modeling of acetate metabolism in the human brain

Abstract

Most 13C metabolic modeling studies have been performed using 13C‐glucose as the infused substrate. Acetate, a glial‐specific substrate, is an attractive alternative to glucose to study neuronal‐glial interactions [1,2]. The goals of the present study were to determine kinetic parameters for acetate transport and utilization and to perform dynamic metabolic modeling of glutamate and glutamine 13C turnover curves obtained during [2–13C]acetate infusion in the human brain with a two‐compartment neuronal‐glial model.ResultsFitted values for acetate transport and uptake kinetics were: Vtrmax=0.300.07 μmol/g/min and Vutmax=0.170.03 μmol/g/min [3]. Metabolic fluxes determined from metabolic modeling of the glutamate and glutamine positional 13C time courses were (in μmol/g/min): VTCA(n)=0.680.20, VTCA(g)=0.090.02, VPC=0.000.01, VX=0.830.20 and VNT=0.140.03. These values are in agreement with rates reported in previous studies [2,4].ConclusionDynamic metabolic modeling of glutamate and glutamine 13C turnover curves measured during [2–13C]acetate infusion with a two‐compartment neuronal‐glial model is feasible and allows determination of compartmentalized metabolic rates in human brain.