Tyrosine hydroperoxide formation

Nitric oxide released by macrophages during inflammation reacts with active oxygen to form peroxynitrite. Peroxynitrite nitrates protein and peroxidizes lipids. y-Tocopherol (the principal form of vitamin E in the United States diet) and a-tocopherol (the major form present in the European diet and in supplements), both protect against peroxynitrite-induced lipid oxidation. [13]. Christen et al. reported that lipid hydroperoxide formation in liposomes is inhibited more effectively by y-tocopherol than a-tocopherol by a non-antioxidant mechanism [14]. However, Goss et al. [15] concluded that the presence of a-tocopherol attenuates nitration of both y-tocopherol and tyrosine, showing that nitration of... 

Fig. 7. Oxidation products of proteins. The vertical structure in the middle represents the main peptide chain with amino acid side groups extending horizontally (M2). The a-carbons in the primary chain can be oxidized to form hydroperoxides. Reactions on the right side near the top exemplify oxidation of the primary chain leading to a peroxyl radical. Side chains represented are lysine, methionine, tyrosine, cysteine, and histidine, top to bottom, respectively. Modifications of the side chains and primary chain lead to carbonyl formation and charge modifications. If these reactions are not detoxified by antioxidants, they may propagate chain reactions within the primary chain, leading to fragmentation of the protein. See the text for details, o, represents reaction with oxygen RNS, reactive nitrogen species ROS, reactive oxygen species. Dense dot represents unpaired electron of radical forms.

Lipoxygenase (LOX) converts polyunsaturated fatty acids, such as linoleic and linolenic acids, to lipid hydroperoxides (Figure 2)(52,73,74). The lipid hydroperoxides then form hydroperoxide radicals, epoxides, and/or are degraded to form malondialdehyde. These products are also strongly electrophilic, and can destroy individual amino acids by decarboxylative deamination (e.g., lysine, cysteine, histidine, tyrosine, and tryptophan) cause free radical mediated cross-linking of protein at thiol, histidinyl, and tyrosinyl groups and cause Schiff base formation (e.g., malondialdehyde and lysine aldehyde) (39,49,50,74-78). 

An enzyme-substrate complex has been detected in the oxidative dimerization of L-(-)-tyrosine by HRP(i) to give HRP(ii). The pH dependence of the reaction reveals an enzyme protonation at pATa 5.42 with a less reactive protonated form. The hydroperoxide of indole-3-acetic acid (lAA) is important in the autoxidation of lAA catalysed by HRP. Formation of HRP(i) by reaction with the hydroperoxide is easier for the neutral isoenzyme than for the acidic species at pH 4.4 and this determines the catalytic activity. HRP(ii) is detected as an intermediate in the reaction and it reacts with lAA to form radicals. The involvement of both HRP(i) and HRP(ii) is proposed in the autoxidation of 2-nitro-propane to acetone and HNO2, catalysed by HRP. 

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