L-[2,5-H2]phenylalanine, an alternate substrate for rat liver phenylalanine hydroxylase.
The phenylalanine analogue L-[2,5-H2]phenylalanine (1) was found to be a viable substrate (KM = 0.45 mM, kcat = 8 s-1) for L-phenylalanine-activated, rat liver phenylalanine hydroxylase (EC 1.14.16.1) (PAH). The PAH-catalyzed oxidation of 1 was stoichiometric with the oxidation of cofactor, 6-methyl-tetrahydropterin. Spectral and chromatographic data of the product from the oxidation of 1 by PAH were found to be in accord with a 3,4-epoxide. The enzymatic epoxidation of 1 is consistent with the hypothesis of an intermediate arene oxide on the reaction coordinate for PAH hydroxylation of L-phenylalanine.
Miller
R J
RJ
Department of Chemistry, Pennsylvania State University, University Park 16802.
Benkovic
S J
SJ
D000818:Animals; D053138:Cyclohexenes; D007202:Indicators and Reagents; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D010651:Phenylalanine Hydroxylase / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D013379:Substrate Specificity
D053138:Cyclohexenes; D007202:Indicators and Reagents; C004174:2,5-dihydrophenylalanine; D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase