Metabolism of gamma-hydroxy-[1-14C] butyrate by rat brain: relationship to the Krebs cycle and metabolic compartmentation of amino acids.

Abstract

Abstract— Ninhydrin decarboxylation experiments were carried out on the labelled amino acids produced following intraventricular injection of either γ‐hydroxy‐[1‐14C]butyric acid (GHB) or [1‐14C] succinate. The loss of isotope (as 14CO2) was similar for both substances. The [1‐14C]GHB metabolites lost 75% of the label and the [1‐14C] succinate metabolites lost 68%. This observation gives support to the hypothesis that the rat brain has the enzymatic capacity to metabolize [1‐14C]GHB to succinate and to amino acids that have the isotope in the carboxylic acid group adjacent to the a‐amino group. These results also indicate that the label from [1‐14C]GHB does not enter the Krebs cycle as acetate. The specific activity ratio of radiolabelled glutamine to glutamic acid was determined in order to evaluate which of the two major metabolic compartments preferentially metabolize GHB. It was found that for [1‐14C]GHB this ratio was 4.20 ± 0.18 (S.E. for n = 7) and for [l‐14C]succinate this ratio was 7.71 (average of two trials, 7.74 and 7.69). These results suggest that the compartment thought to be associated with glial cells and synaptosomal structures is largely responsible for the metabolism of GHB. Metabolism as it might relate to the neuropharmacological action of GHB is discussed.