Biosynthesis of tetrahydrobiopterin in man

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1985
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Curtius, Hans-Christoph
Heintel, Dorothee
Kuster, Thomas
Leimbacher, Walter
Niederwieser, Alois
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Journal of Inherited Metabolic Disease. 1985, 8(Suppl. 1), pp. 28-33. Available under: doi: 10.1007/978-94-011-8019-1_6
Zusammenfassung

The biosynthesis of tetrahydrobiopterin (BH4) from dihydroneopterin triphosphate (NH2P3) was studied in human liver extract. The phosphate-eliminating enzyme (PEE) was purified ~750-fold. The conversion of NH2P3 to BH4 was catalyzed by this enzyme in the presence of partially purified sepiapterin reductase, Mg2+ and NADPH. The PEE is heat stable when heated at 80°C for 5 min. It has a molecular weight of 63 000 daltons. One possible intermediate 6-(1prime-hydroxy-2prime-oxopropyl)5,6,7,8- tetrahydropterin(2prime-oxo-tetrahydropterin) was formed upon incubation of BH4 in the presence of sepiapterin reductase and NADP+ at pH 9.0. Reduction of this compound with NaBD4 yielded monodeutero threo and erythro-BH4, the deuterium was incorporated at the 2prime position. This and the UV spectra were consistent with a 2prime-oxo-tetrahydropterin structure. Dihydrofolate reductase (DHFR) catalyzed the reduction of BH2 to BH4 and was found to be specific for the pro-R-NADPH side. The sepiapterin reductase catalyzed the transfer of the pro-S hydrogen of NADPH during the reduction of sepiapterin to BH2. In the presence of crude liver extracts the conversion of NH2P3 to BH4 requires NADPH. Two deuterium atoms were incorporated from (4S-2H)NADHP in the 1prime and 2prime position of the BH4 side chain. Incorporation of one hydrogen from the solvent was found at position C(6). These results are consistent with the occurrence of an intramolecular redox exchange between the pteridine nucleus and the side chain and formation of 6-pyruvoyl-5,6,7,8-tetrahydropterin(tetrahydro-1prime-2prime-dioxopterin) as intermediate.

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570 Biowissenschaften, Biologie
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ISO 690CURTIUS, Hans-Christoph, Dorothee HEINTEL, Sandro GHISLA, Thomas KUSTER, Walter LEIMBACHER, Alois NIEDERWIESER, 1985. Biosynthesis of tetrahydrobiopterin in man. In: Journal of Inherited Metabolic Disease. 1985, 8(Suppl. 1), pp. 28-33. Available under: doi: 10.1007/978-94-011-8019-1_6
BibTex
@article{Curtius1985Biosy-7027,
  year={1985},
  doi={10.1007/978-94-011-8019-1_6},
  title={Biosynthesis of tetrahydrobiopterin in man},
  number={Suppl. 1},
  volume={8},
  journal={Journal of Inherited Metabolic Disease},
  pages={28--33},
  author={Curtius, Hans-Christoph and Heintel, Dorothee and Ghisla, Sandro and Kuster, Thomas and Leimbacher, Walter and Niederwieser, Alois}
}
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