Biosynthesis of tetrahydrobiopterin in man

Curtius, Hans-Christoph; Heintel, Dorothee; Ghisla, Sandro; Kuster, Thomas; Leimbacher, Walter; Niederwieser, Alois

Biosynthesis of tetrahydrobiopterin in man

Dateien

ghislascan180.pdfGröße: 329.12 KBDownloads: 444

Datum

1985

Autor:innen

Curtius, Hans-Christoph

Heintel, Dorothee

Ghisla, Sandro

Kuster, Thomas

Leimbacher, Walter

Niederwieser, Alois

Open Access-Veröffentlichung

Open Access Green

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

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.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

CURTIUS, 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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