Biopterin : II. Evidence for cerebral synthesis of 7,8-dihydrobiopterin in vivo and in vitro.

The active synthesis of [(14)C]7,8-dihydrobiopterin (BH2) from intraventricularly administered U-[(14)C]GTP was demonstrated in rat brain. The identity of [(14)C]BH2 isolated from brain was confirmed by mass fragmentography. Evidence is presented that [(14)C]BH2 in brain was not synthesized in the peripheral organs. The rate of cerebral synthesis of [(14)C]BH2 from [(14)C]GTP was maximal at 2 h; it was 0.53 nmol/g per h, which is consistent with the estimated turnover rate of cerebral BH2 (0.43 nmol/g per h). Intraventricularly injected 2,4-diamino-6-hydroxypyrimidine (DAOPyr) and 6-thioguanosine were effective inhibitors of the synthesis. U-[(14)C]dGTP and 8-[(14)C]GTP, when given intraventricularly, did not yield [(14)C]BH2. Simultaneous intraventricular injection of U-[(14)C]GTP and DAOPyr resulted in the accumulation of a compound with properties identical to a formamidopyrimidine derivative isolated from the nonenzymatic hydrolysis of GTP. The data from preliminary experiments demonstrated the synthesis of [(14)C]BH2 from U-[(14)C]GTP incubated with 12,000g supernatants of rat brain homogenates.