Glutamine transport in brain mitochondria.

Gln is transported into rat brain synaptic and non-synaptic mitochondria by a protein catalyzed process. The uptake is significantly higher in synaptic than in non-synaptic mitochondria. The transport is inhibited by the amino acids Glu, Asn and Asp, and by the TCA cycle intermediates succinate, malate and 2-OG. The inhibition by 2-OG is counteracted by AOA and is therefore assumed to be due to transamination of 2-OG, whereby Glu is formed. This presumes that Glu also binds to an inhibitory site on the matrix face of the inner membrane. The transport is complex and cannot be explained by the simple uniport mechanism which has been proposed for renal (Schoolwerth and LaNoue, 1985), and liver mitochondria (Soboll et al., 1991). Thus, Gln transport is stimulated by respiration and by the proton electrochemical gradient. Since it is indicated that both the neutral Gln zwitterion and the Gln anion are transported, there are probably different uptake mechanisms, but not necessarily different carriers. Gln may be transported by an electroneutral mechanism as a proton compensated anion, as well as electrophoretically as a zwitterion with a proton, and probably also by diffusion as a zwitterion. The properties of the brain mitochondrial Gln uptake mechanisms are also not identical with those of a purified renal Gln transporter. It is possible that the Gln transport is controlled by more than one protein, which may be situated on distinct species in a heterogeneous mitochondrial population. Since Gln is assumed to participate in energy production as well as in the synthesis of nucleic acid components and proteins in brain mitochondria, the control of Gln uptake in these organelles may be important.