Tyrosine phenoxyl

Phenoxyl radicals are oxidizing radicals (for a compilation of redox potentials see Wardman 1989). Thus, in their reactions with 02 (E7 = -0.3 V) there is ample driving force for a reduction by ET [cf. reaction (16)], and this has been thought for a long time to be the only (Hunter et al. 1989) or at least a major process, depending on the reduction potential of the (substituted) phenoxyl radical (Jonsson et al. 1993). Yet in the tyrosine system, despite of the high reduction potential of tyrosine phenoxyl radical (E7 = 0.64 V), the by far dominating process is addition, and the intermediate adduct is locked in by a Mannich reaction [reactions (14) and (15) Jin et al. 1993],... 

Hug GL, Bonifacic M, Asmus K-D, Armstrong DA (2000a) Fast decarboxylation of aliphatic amino adds induced by 4-carboxybenzophenone triplets in aqueous solutions. A nanosecond laser flash photolysis study. J Phys Chem B 104 6674-6682 Hug GL, Carmichael I, Fessenden RW (2000b) Direct EPR observation of the aminomethyl radical during the radiolysis of glycine. J Chem Soc Perkin Trans 2 907-908 Hunter EPL, DesrosiersMF, Simic MG (1989) The effect of oxygen, antioxidants and superoxide radical on tyrosine phenoxyl radical dimerization. Free Rad Biol Med 6 581-585 Ito O (1992) Flash photolysis study for reversible addition reactions of thiyl radicals with olefins and acetylenes. Trends Phys Chem 3 245-266... 

Hunter EPL, Desrosiers MF, Simic MG (1989) The effect of oxygen, antioxidants and superoxide radical on tyrosine phenoxyl radical dimerization. Free Rad Biol Med 6 581-585... 

EPR spectroscopy has demonstrated that the oxidation of the globin occurs ultimately at a tyrosine residue, resulting in the formation of a tyrosine-phenoxyl radical this species is postulated to react subsequently with oxygen to give a tyrosine-peroxyl radical. Studies have shown that both of these species are accessible to components in bulk solution, i.e. they are located on the surface of the protein [47-49]. Ferryl haem protein radical from myoglobin and haemoglobin can react with membranes [33,45,50] and lipoproteins [51-... 

It has been proposed that the second oxidizing equivalent is accepted by tyrosine-103 on the surface of the protein (Ortiz de Montel-lano, 1983) forming a tyrosine phenoxyl radical which rapidly takes up oxygen forming the peroxyl species (Davies, 1990) as depicted in Fig. 4.4. 

Fig. 4.4. Scheme for postulated formation of the tyrosine phenoxyl and peroxyl radical... 

Fig. 16. Spectroscopic characterization of the oxidized apogalactose oxidase free radical, (a) Optical absorption spectrum for the radical-containing apoprotein, (b) X-band EPR spectrum of the metal-free protein following Ir(IV) oxidation, (c) Expansion of the region near g = 2 comparing experimental data (Exp) with a theoretical simulation (Sim) based on coupling of the unpaired electron spin with one and one Hp proton of a tyrosine phenoxyl. Simulation parameters g = 2.0017, g2 = 2.0073 Ai Ha) = 8.4 G, A2(Hc,) = 8.8 G di(Hp) = 12.7 G, A2(Hp) = 13.8 G.

This is markedly different from the behavior of a simple tyrosine phenoxyl, such as that found in ribonucleotide reductase, whose spectrum exhibits a strong rhombic splitting (Fig. 17, line c) but precisely the same as observed for the 0-methylthiocresyl model radical (Fig. 17, line b). This clearly identihes the Tyr-Cys side chain as the site of the oxidized apoGAOX radical and demonstrates that the electronic structure of the thioether-substituted phenoxyl is distinct from that of a simple phenoxyl radical. 

It has been shown by pulse radio lysis that in peptides and enzymes containing both tryptophan (Trp) and tyrosine (Tyr) the radical produced by oxidation of tryptophan can efficiently oxidize tyrosine to yield the tyrosine phenoxyl radical TyrO (equation 17) ... 

Fit . 4. EPR spectrum observed immediately after mixing soybean Fe(III) Lb (250 fj.M) with HA (250 p,M) at pH 7.4. Reaction studied using a two-way stopped-flow mixing system inserted into the cavity of the EPR spectrometer. The signal is assigned to a sterically constrained tyrosine phenoxyl radical formed at position 133 (reproduced with permission from Davies, M. J. Puppo, A. Biochem. J. 1992, 281, 197—201). 

The main source of thiyl radicals in cells is expected to be reaction (1), because of the relative abundance of C-H bonds. Some biological radicals are nitrogen-or oxygen-centered, such as the tryptophan (indolyl) radical in DNA photolyase [45], and indolyl and tyrosine (phenoxyl) radicals in ribonucleotide reductase [46-49]. Whether oxygen-centred radicals such as phenoxyl radicals (PhO, e.g. from tyrosine) oxidize GSH by hydrogen transfer ... 

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