Tetrahydrobiopterin is synthesized from 6-pyruvoyl-tetrahydropterin by the human aldo-keto reductase AKR1 family members

Archives of Biochemistry and Biophysics
T IinoAkira Hara

Abstract

Tetrahydrobiopterin (BH(4)) is a cofactor for aromatic amino acid hydroxylases and nitric oxide synthase. The biosynthesis includes two reduction steps catalyzed by sepiapterin reductase. An intermediate, 6-pyruvoyltetrahydropterin (PPH(4)) is reduced to 1(')-oxo-2(')-hydroxypropyl-tetrahydropterin (1(')-OXPH(4)) or 1(')-hydroxy-2(')-oxopropyl-tetrahydropterin (2(')-OXPH(4)), which is further converted to BH(4). However, patients with sepiapterin reductase deficiency show normal urinary excretion of pterins without hyperphenylalaninemia, suggesting that other enzymes catalyze the two reduction steps. In this study, the reductase activities for the tetrahydropterin intermediates were examined using several human recombinant enzymes belonging to the aldo-keto reductase (AKR) family and short-chain dehydrogenase/reductase (SDR) family. In the reduction of PPH(4) by AKR family enzymes, 2(')-OXPH(4) was formed by 3 alpha-hydroxysteroid dehydrogenase type 2, whereas 1(')-OXPH(4) was produced by aldose reductase, aldehyde reductase, and 20 alpha-hydroxysteroid dehydrogenase, and both 1(')-OXPH(4) and 2(')-OXPH(4) were detected as the major and minor products by 3 alpha-hydroxysteroid dehydrogenases (types 1 and 3). The activities of a...Continue Reading

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Citations

Oct 18, 2011·ACS Chemical Biology·Gabriela PhillipsValérie de Crécy-Lagard
May 13, 2011·Journal of Natural Products·Mayuko TakemuraAkira Hara
Nov 11, 2010·The Journal of Biological Chemistry·Daigo HommaHiroshi Ichinose
Apr 14, 2011·The Journal of Biological Chemistry·Tatsiana RakovichVincent P Kelly
May 27, 2008·Molecular Genetics and Metabolism·Marcel M VerbeekDimitrios I Zafeiriou
Jan 19, 2008·Biochemical and Biophysical Research Communications·Chisato TakazawaSetsuko Katoh
Jun 7, 2007·The Plant Journal : for Cell and Molecular Biology·Alexandre NoirielAndrew D Hanson
Aug 27, 2011·The Biochemical Journal·Ernst R WernerBeat Thöny
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Apr 14, 2012·Drug Metabolism and Pharmacokinetics·Toshiyuki MatsunagaAkira Hara
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Sep 27, 2016·Archives of Biochemistry and Biophysics·Akira HaraKoji Yashiro
Aug 1, 2020·Journal of Cellular and Molecular Medicine·Yao WuMeixiao Zhan
Apr 8, 2020·Biochemical and Biophysical Research Communications·Akira HaraSatoshi Endo
Apr 28, 2021·Molecular Genetics and Metabolism·Nastassja HimmelreichBeat Thöny

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