title: Phenylalanine hydroxylase: absolute configuration and source of oxygen of the 4a-hydroxytetrahydropterin species.
abstract: 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.
mesh_terms: D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D008401:Gas Chromatography-Mass Spectrometry; D008099:Liver / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D009904:Optical Rotation; D010651:Phenylalanine Hydroxylase / Q000378:metabolism*; D011621:Pteridines / Q000378:metabolism*; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D011621:Pteridines; D001708:Biopterins; D010651:Phenylalanine Hydroxylase; C003402:sapropterin