The occurrence of coenzyme A (CoA) in the amount of 42-88 nmol/g wet tissue in the large hemispheres (Deutsch, 2002, 2003) suggests an in situ system of coenzyme biosynthesis from the vitamin precursor, L-cysteine, and ATP in which production and biotransformation of 4'-phosphopantothenic acid (PPA) play a key role. The biotransformation of [³H]PPA, obtained by thermal activation of tritium with the specific activity of 9.8 GBq/mmol, was studied after its cerebroventricular administration (0.6 μCi, uni-or bilaterally) to Wistar male rats. After 10-20 min following the administration, cerebrospinal fluid showed unchanged PPA. In total, brain structures retained up to 39-42% of the radionuclide (10-20 min), and after 6 h, the radionuclide content was decreased down to 17%, which was not accompanied by a significant radioactivity release into the blood circulation. [³H]PPA biotransformation was studied by HPLC of tissue perchlorate extracts in the regimen of isocratic elution on a column filled with reverse-phase sorbent (Separon SGX C₁₈). A preparation synthesized at our laboratory was used as standard. The radionuclide distribution among brain structures was investigated using HPLC of tissue perchlorate extracts. Twenty minutes after the radionuclide administration, the structures with high [³H]PPA uptake (large hemisphere cortex, brain stem) showed the following metabolites: PPA, 20 %, pantothenic acid (PA), 58%, phosphopantetheine (PP-SH), 18%, and CoA, 3%. Within the subsequent periods (3-6 h) the PPA fraction was reduced, whereas the PA fraction was increased up to 64-77% and the PP-SH and CoA fractions remained at the initial levels. In other structures (cerebellum, hyppocampus, frontal cortex), the radionuclide distribution was the same, with 41 and 28% of PPA being revealed in the hyppocampus after 10 and 20 min, respectively. The PPA level in the large hemisphere cortex was somewhat lower: 37 and 20%, respectively. A maximally decreased PPA fraction was found in the large hemisphere cortex and cerebellum, whereas a maximally increased PP-SH fraction was detected in the brain stem and cerebellum 6h after the administration. At that period the CoA fraction accumulated from 1.5 to 5% of tissue radioactivity. The results suggest that [³H]PPA absorption by brain structures was accompanied by rapid dephosphorylation of the compound with concomitant (subsequent) phosphorylation in a pantothenate kinase reaction and further use by CoA biosynthetic enzymes and/or PPA absorption by brain structures and its rapid utilization by a direct conjugation with cysteine in a phosphopantothenoyl-L-cysteine synthetase reaction. Our findings confirm a key role of PPA or its metabolism to PP-SH in CoA system stabilization in neurostructures.

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