Cerebral Metabolism of Amino Acids and Related Metabolites as Studied by C-13 andC-14 Labelling

摘要

The present investigations show the feasibility of analyzing the cerebralmetabolism of amino acids and related metabolites by C-13 and C-14 labelling using labelled acetate and glucose as markers for glial and neuronal metabolism, respectively. Using (C-13) acetate, it was shown that glial cells export approximately 60% of their TCA cycle intermediates, mostly as glutamine, and that this glutamine is used by neurons partly as an energy reserve, partly it is converted directly to glutamate and GABA. Using (C-13) glucose, the glial process of pyruvate carboxylation was shown to compensate fully for the loss of glutamine. The mechanism of action of two neurotoxins, fluorocitrate and 3-nitropropionate, was elucidated. The latter toxin was shown to inhibit the TCA cycle of GABAergic neurons selectively. Formation of pyruvate and lactate from glial TCA cycle intermediates was demonstrated in vivo. This pathway may be important for the glial inactivation of transmitter glutamate and GABA. The results illustrate glianeuronal interactions, and they suggest the applicability of C-13 NMR spectroscopy to the detailed study of the cerebral metabolism of amino acids in the intact, unanesthetized human brain.