Glutamine, glutamate, and GABA in the central nervous system pages 205-217




The concept of metabolic compartmentation describes the presence in a tissue of functionally different and chemically distinct pools of a given substrate. These separate pools equilibrate only very slowlyt if at a11, and exhibit different turnover and flux rates. Such heterogeneous functional pools of amino acids were coming under investigation in microorganisms (Britten et al. 1955; Cowie, Walton 1956; Cowie, McClure 1959), plants (Steward et al. 1956; Maclennan et al. 1963), and animal tissues (Korner, Tarver 1957; Green, Lowther 1959; Kipnis et al. 1961) at about the same time that we began our studies on glutamate-glutamine metabolism in brain. The first reference to the term metabolic compartmentstion trat we have noted is in the work of Stuart et al. (1956). In their studies on the carrot root explant, they found that glutamic acid derived from [U-l4C]glutamine had a higher specific activity (counts/min/μmol, SA) than the glutamine isolated from the tissue, a situation opposite to that which prevails in brain. They deduced that there were two separate pools of glutamine, only one of which was active in qlutamate synthes~s. Their studies with the growing carrot root also demonstrated · that [14C]glucose labeled - more readily protein glutamic acid than did [14C]glutamine. GABA was also shown to be readily converted to qlutamic acid and glutamine. Our studies with brain led to the conclusion that compartmentation of metabolic events was the most logical explanation of the phenomena we were observing

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