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Best-Fit Analysis of Kinetic Scheme for the Stepwise Reduction of the “Diketo” Group of 6-Pyruvoyl Tetrahydropterin by Sepiapterin Reductase

  • Terumi Sueoka
  • Harumi Hikita
  • Setsuko Katoh
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 284)

Abstract

Sepiapterin reductase [EC 1 .1.1.153](SPR) is an enzyme required in the biosynthesis of tetrahydrobiopterin (Katoh and Akino, 1986), an essential H-donor cofactor of aromatic amino acid hydroxylases such as tyrosine hydroxylase (Kaufman, 1986). Recently we found (Katoh and Sueoka, 1984; Sueoka and Katoh, 1985) that this enzyme belongs to the “Aldo-keto reductases” group (Tuner and Flynn, 1982; Wermuth, 1985). SPR can reduce various carbonyl compounds including “diketo-” compounds such as phenylpropanedione and diacetyl with NADPH (Katoh and Sueoka, 1984). The natural substrate of this enzyme, 6-pyruvoyl tetrahydropterin(6(R)-L-1′,2′-dioxopropyl 5,6,7,8-tetrahydropterin)(PPH4) is also a “diketo-” compound, and the vicinal “diketo” group (C1′-keto and C2′-keto) in the molecule was found to be reduced successively with NADPH by SPR to a “dihydrodiol” group to form tetrahydrobiopterin (BH4) (Masada et al., 1985: Curtius et al., 1985; Milstien and Kaufman, 1985; Brown et al., 1985; Smith and Nichol, 1986). In the previous works, only one type of mono-keto derivative (C2′-keto type) was found as the intermediate of SPR during the reduction of PPH4 at the usual assay pH (neutral pH). But recently we detected both types of the mono-keto derivatives (C1′-keto type and C2′-keto type) as the intermediate of the reaction if the reaction was performed at a pH lower than neutral (Katoh and Sueoka, 1990)(Fig. 1).

Keywords

Tyrosine Hydroxylase Kinetic Scheme Guanosine Triphosphate Sepiapterin Reductase Aromatic Amino Acid Hydroxylase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Terumi Sueoka
    • 1
  • Harumi Hikita
    • 2
  • Setsuko Katoh
    • 1
  1. 1.Department of BiochemistryMeikai University School of DentistrySakado, Saitama 350-02Japan
  2. 2.Laboratory of PhysicsMeikai UniversityUrayasu Chiba, 279Japan

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