Uptake and metabolism of Δ 1-piperidine-2-carboxylic acid by synaptosomes from rat cerebral cortex

Abstract

Δ 1-Piperidine-2-carboxylic acid (P2C), an intermediate of the l-lysine metabolic pathway in the brain, was studied for its uptake metabolism in the synaptosome of the rat cerebral cortex. The results of this study showed that the uptake of P2C into the synaptosome was NA +-and temperature-dependent with a two-tier transport kinetic ( K m = 2.6 and 0.7 μM; V max = 1.6 and 0.73 pmol/min/mg). P2C uptake was only moderately inhibited (≈20%) by l-lysine and its metabolites, l-α-aminoadipic acid at up to 100 μM, and the putative amino acid neurotransmitters, γ-aminobutyric acid, l-glutamic acid and l-spartic acid (25–31%) at 5–500 μM. The synaptosomal preparation only has a very low activity for metabolizing P2C to its product l-pipecolic acid. The metabolic activity for P2C was mainly contained in the 27 000 × g supernatant S 2 fraction. Since P2C is the precursor of the putative neuromodulator l-pipecolic acid, the understanding of its uptake and metabolic characteristics in the brain should be of significance.