Absorption and biotransformation of the coenzyme A precursor D-pantethine in rat hippocampus

We injected albino rats intraperitoneally with D-[ 3 H]-pantethine at a dose of 15 mg/kg of body weight (0.014 Ci/mmol) or perfused rat hippocampal slices with 47 μM (1.3 Ci/mmol) solution of this substance. Using reversed phase HPLC, we found that metabolic products of D-pantethine, including phosphopantothenate and pantothenate, were rapidly absorbed from blood serum and retained in the hippocampus. We also observed their limited biotransformation in the system of coenzyme A (CoA) biosynthesis with the formation of 4′-phosphopantetheine and CoA 10 min to 24 h after radionuclide administration. Hippocampal slices were perfused for 3–7 min. In the fractions that were eluted with 8.5% methanol, we found 4′-phosphopantetheine/pantetheine (64–47%), pantothenate (18–15%), phosphopantothenate (9–18%), and CoA (7–10%). The decrease in the radionuclide-retaining capacity in the slices was associated with a linear increase in the 4′-phosphopantothenate fraction. The role of 4′-phosphopantothenate in the stabilization of the CoA level and mechanisms of neuroprotection in the hippocampus, as well as the potential for the use of pantethine-based drugs in neurological practice are discussed.