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Measurement of Biopterin and the Use of Inhibitors of Biopterin Biosynthesis

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Book cover Nitric Oxide Protocols

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 100))

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Abstract

Tetrahydrobiopterin (BH4) and related pteridines have received much attention since BH4 was found to be an essential cofactor for nitric oxide synthases (NOS) (1–3). As shown in Fig. 1, BH4 is produced from guanosine 5′-triphosphate (GTP) by three enzymes. GTP cyclohydrolase I converts GTP to dihydroneopterin triphosphate, which is then converted to 6-pyruvoyltetrahydropterin by 6-pyruvoyltetrahydropterin synthase. This second unstable intermediate compound is converted to BH4 through a two-step reduction of its side-chain carbonyl groups by sepiapterin reductase.

Proposed scheme for BH4 metabolism. The reactions of tyrosine hydroxylase, tryptophan hydroxylase, and NOS are not shown. The route for the conversion of 6-pyruvoyl-tetrahydropterin to BH4 is controversial (5,45). Recent best-fit analysis of kinetic data for sepiapterin reductase (EC 1.1.1.153) (46) suggests that the following route is predominant: 6-pyruvoyl-tetrahydropterin is reduced at the 2′-oxo group to form 6-(1′-oxo-2′-hydroxypropyl)-tetrahydropterin (also called 6-lactoyl-tetrahydropterin) by sepiapterin reductase. Then, 6-(1′-oxo-2′-hydroxypropyl)-tetrahydropterin is isomerized by sepiapterin reductase to 6-(1′-hydroxy-2′-oxopropyl)-tetrahydropterin, which is reduced again at the 2′-oxo group by sepiapterin reductase. The conversion of 6-pyruvoyltetrahydropterin to 6-(1′-oxo-2′-hydroxypropyl)-tetrahydropterin is also catalyzed by aldose reductase (EC 1.1.1.21) (47, 48). Regarding the salvage pathway from sepiapterin to BH4, see the text.

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Authors and Affiliations

  1. Department of Surgery, University of Pittsburgh, Pittsburgh, PA

    Kazuyuki Hatakeyama

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  1. Kazuyuki Hatakeyama
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  1. University of Sussex, Brighton, UK

    Michael A. Titheradge

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© 1998 Humana Press Inc.

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Hatakeyama, K. (1998). Measurement of Biopterin and the Use of Inhibitors of Biopterin Biosynthesis. In: Titheradge, M.A. (eds) Nitric Oxide Protocols. Methods in Molecular Biology™, vol 100. Humana Press. https://doi.org/10.1385/1-59259-749-1:251

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  • DOI: https://doi.org/10.1385/1-59259-749-1:251

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-470-9

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