Compartmentalized neurotransmitter and amino acid synthesis in vivo studied by high field MRS

Abstract

Glutamatergic action occurs by the glial uptake of extracellular glutamate and conversion into glutamine, which is exported to neurons. Recently, a 1 : 1 stoichiometry between total oxidative brain glucose consumption, CMRglc(ox), and glutamatergic action was reported. This relationship required, that all of the glucose phosphorylated in glia was exported to neurons in the form of lactate. We recently reaffirmed in the awake human brain that the majority of ATP produced in glia is oxidative (Gruetter et al. 2001). In that study we also observed that the exchange rate between TCA cycle intermediates and amino acids, Vx, is on the order of the flux through pyruvate dehydrogenase, VPDH, which implied that this exchange rate is influenced by the malate–aspartate shuttle (MAS). Recently we have extended this line of investigation to the intact rat brain. TCA cycle flux and glutamate/glutamine metabolism was assessed in vivo at two different anesthetic levels (pentobarbital and α‐chloralose anesthesia) using 13C NMR in conjunction with 13C glucose infusions. Several metabolic rates were extracted from the rate of label incorporation using a mathematical model (Gruetter et al. 2001). The apparent rate of glutamatergic neurotransmission, VNT, was low, even though glucose metabolism was still substantial, suggesting that the stoichiometry between glucose metabolism and glutamatergic neurotransmission is far from 1 : 1. The rate of pyruvate carboxylation was ∼25% of glutamine synthase flux. Vx was found to be equal to VPDH, indicating that Vx is coupled to CMRglc(ox), consistent with MAS being the major mechanism that facilitates label exchange across the inner mitochondrial membrane.Reference Gruetter et al. (2001) Am. J. Physiol.281, 100E.