Mechanism of Oxidation of Tetrahydropterins

Abstract

The oxidation of tetrahydropterins and 7,8-dihydropterins by ferric iron has been examined by both polarographic and spectral techniques. Quinonoid dihydropterin, an intermediate in the oxidation of the tetrahydropterins, is formed rapidly, as is ferrous iron. The quinonoid dihydropterin then rearranges to 7,8-dihydropterin. The rate of oxidation of 7,8-dihydropterins is much slower than that of tetrahydropterins. The reduction potential of the reversible quinonoid dihydropterin – tetrahydropterin couple has been measured and shown to be consistent with the known chemistry of these compounds. Kinetic measurements and structural studies have been used to formulate a mechanism for the oxidation of tetrahydropterins to quinonoid dihydropterins. This mechanism involves abstraction of an electron from position 5, followed by rapid loss of two protons and the other electron.

H2O2‐mediated oxidation of tetrahydrobiopterin: Fourier transform Raman investigations provide mechanistic implications for the enzymatic utilization and recycling of this essential cofactor

“…Several pathways for the subsequent oxidation of qBH 2 have been determined using different reaction conditions yielding concomitant rearrangement and oxidation of the pyrazine ring and also elimination of the dihydroxypropyl side-chain from position 6 of the pyrazine ring of 6BH 4 . The rearrangement of the quinonoid dihydro species yielding a dihydropterin without loss of the substituent in position 6 of the pyrazine ring has already been established by Archer et al 11 However, in all reports the final product was a fully oxidized pterin ring system. Recently, the oxidation of 6BH 4 has been studied with peroxynitrite and H 2 O 2 , but the authors claimed that peroxynitrite oxidizes 6BH 4 whereas H 2 O 2 does not.…”

Tetrahydrobiopterin, a cofactor for rat cerebellar nitric oxide synthase, does not function as a reactant in the oxygenation of arginine.

“…There is only a small likelihood that H2B is acting as a reductant of NOS. Whereas 7,8-dihydropterins can reduce ferric iron, the rate of this reaction at pH 6.4 is at least 3 orders of magnitude less than the corresponding rate with tetrahydropterins (35). Further, H2B typically acts as a biochemical oxidant (in the reaction catalyzed by DHFR), and no biological reaction is known in which H2B acts as a reductant.…”

Purification and Properties of a Folate-catabolizing Enzyme

“…The quinazoline ring can be sequentially oxidized to dihydrofolate and then to folic acid through a quinonoid dihydrofolate intermediate (5,6). This mechanism is also shared by tetrahydropterin oxidation (7,8). The site of oxidation has been proposed to occur through a 4a-carbinolamine intermediate, and chemically stable deazatetrahydropterin 4a adducts have been synthesized (7) and shown to be analogous to intermediates associated with the nonenzymatic oxidation of tetrahydropterins.…”