Synthesis of 4′-[³H]-Phospho-pantothenic acid and studies of its metabolism in structures of the brain

Abstract

[³H]-Phospho-pantothenic acid ([³H]-PhPa) was synthesized by the method of heat activation of tritium with a specific radioactivity of 9.8 GBq/mmol. Distribution, transport, and biotransformation of [³H]-PhPA were studied after its intracerebroventricular administration (unilateral and bilateral) to male rats of the Wistar line at a dose of 0.6 μCi. Unchanged [³H]-PhPA was detected in the cerebro-spinal fluid 10–20 min after the administration. [³H]-PhPA was absorbed by brain structures with predominantly ipsilateral simultaneous transformation into metabolites in the following sequence: cortex of cerebral hemispheres > hippocampus > brain stem > frontal cortex > and cerebellum. Brain structures held up to 39–42% of the total radionuclide (10–20 min). The content of the radionuclide had decreased to 17% 6 h later. This decrease was not accompanied by a significant efflux of the radioactivity into the blood circulation. The maximum level of [³H]-PhPA was observed in the hippocampus and cortex of the cerebral hemispheres (37–41% of the total radioactivity). Biotransformation of the radionuclide proceeded via dephosphorylation and biosynthesis of phosphopantetheine (12–20%) and CoA (1.5–5%). The possibility of the direct transport of [³H]-PhPA through neuronal membranes and its deposition in the CNS as precursors of biosynthesis of CoA (pantothenate, PhPA, and phosphopantetheine) was proposed.