Best-Fit Analysis of Kinetic Scheme for the Stepwise Reduction of the “Diketo” Group of 6-Pyruvoyl Tetrahydropterin by Sepiapterin Reductase
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).
KeywordsTyrosine Hydroxylase Kinetic Scheme Guanosine Triphosphate Sepiapterin Reductase Aromatic Amino Acid Hydroxylase
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