Peroxidase catalysed aerobic degradation of 5,6,7,8‐tetrahydrobiopterin at physiological pH

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Abstract
The aerobic degradation of 5,6,7,8‐tetrahydrobiopterin at neutral pH is catalysed by peroxidase (EC 1.11.1.7) and provides quinonoid 7,8‐dihydro(6H)biopterin which readily loses the side chain to yield 7,8‐dihydro(3H)pterin. The latter is in equilibrium with trace amounts of 6‐hydroxy‐5,6,7,8‐tetrahydropterin (covalent hydrate) Which is irreversibly oxidised to quinonoid 6‐hydroxy‐7, 8‐dihydro(6H)pterin, and this finally rearranges to 7,8‐dihydroxanthopterin. Spectroscopic evidence (ultraviolet, 1H NMR and 13C NMR) is presented for the reversible addition of water across the 5,6‐double bond of 7,8‐dihydro(3H)pterin. The intermediate quinonoid 6‐hydroxy‐7,8‐dihydro(6H)pterin is a good substrate for dihydropteridine reductase (EC 1.6.99.7) with a Km of 16.3 μM and kcat of 22.5s−1. The rate of aerobic degradation (oxidation and loss of the side chain) of natural (6R)‐5,6,7,8‐tetrahydrobiopterin is several times slower than the rate for the unnatural (6S) isomer. By using a modified assay procedure the kinetic parameters for dihydropteridine reductase are as follows: with (6R)‐7,8‐dihydro(6H)biopterin Km= 1.3μM and kcat= 22.8s−1; with (6S)‐7,8‐dihydro(6H)biopterin Km= 13.5μM and kcat= 51.6s−1; and with (6RS)‐7,8‐dihydro(6H)neopterin km= 19.2μM and kcat= 116s−1.

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