Phenylalanine hydroxylase: absolute configuration and source of oxygen of the 4a-hydroxytetrahydropterin species.

The formation of tyrosine from phenylalanine catalyzed by rat liver phenylalanine hydroxylase is coupled to the generation of a 4a-hydroxy adduct from the requisite tetrahydropterin cofactor. As indicated by its circular dichroism (CD) spectrum, the optical activity of the adduct generated from racemic 6-methyltetrahydropterin requires stereoselectivity of the oxygenation. The absolute configuration of this new stereocenter is 4a(S)-hydroxy-6(RS)-methyltetrahydropterin by analogy to the CD spectrum of one of the four stereoisomers of 5-deaza-4a-hydroxy-6-methyltetrahydropterin. The source of the 4a-hydroxy oxygen is O2, as demonstrated by the observation of a 18O-induced 13C shift in the 13C NMR spectrum of the adduct when generated from [4a-13C]-6-methyltetrahydropterin and 18O2.

[1]  S. Benkovic,et al.  On the mechanism of action of phenylalanine hydroxylase. , 1981, Biochemical Society transactions.

[2]  S. Benkovic,et al.  Phenylalanine hydroxylase: structural determination of the tetrahydropterin intermediates by carbon-13 NMR spectroscopy , 1982 .

[3]  S. Benkovic,et al.  Synthesis of [4a‐13C]‐6‐methyltetrahydropterin , 1982 .

[4]  J. Risley,et al.  /sup 18/O-isotope effect in /sup 13/C nuclear magnetic resonance spectroscopy. 2. The effect of structure , 1980 .

[5]  J. Vederas.  Structural dependence of oxygen-18 isotope shifts in carbon-13 NMR spectra , 1980 .

[6]  D. W. Gray,et al.  A simple purification of phenylalanine hydroxylase by substrate-induced hydrophobic chromatography. , 1979, The Journal of biological chemistry.

[7]  S. Benkovic,et al.  STUDIES ON 6-METHYL-5-DEAZATETRAHYDROPTERIN AND ITS 4A ADDUCTS , 1979 .

[8]  J. Ayling,et al.  Separation and properties of the 6-diastereoisomers of l-erythro-tetrahydrobiopterin and their reactivities with phenylalanine hydroxylase. , 1978, The Journal of biological chemistry.

[9]  V Massey,et al.  Flavin-oxygen derivatives involved in hydroxylation by p-hydroxybenzoate hydroxylase. , 1976, The Journal of biological chemistry.

[10]  R. Weber,et al.  Über Pterinchemie 53. Mitteilung 1. Zur Konformation von 6‐Methyl‐ und 5,6‐Dimethyl‐5,6,7,8‐terahydropterin in wässeriger Lösung , 1975 .

[11]  K. Kuo,et al.  Amino acid analysis. Hydrolysis, ion-exchange cleanup, derivatization, and quantitation by gas-liquid chromatography. , 1974, Journal of chromatography.

[12]  S. Kaufman,et al.  Preparation of 6-substituted pterins via the Isay reaction , 1971 .

[13]  S. Kaufman,et al.  The source of oxygen in the phenylalanine hydroxylase and the dopamine-β-hydroxylase catalyzed reactions , 1962 .