The Effects Of Tyrosine And Histidine On Heme Peroxidase Activity

Heme proteins such as hemoglobin (Hb) have been shown as efficient inducersof oxidative damage in vivo and vitro. The mechanism of this deleterious action islinked to the heme peroxidase activity. In this study, two important amino acids(Tyr and His) were selected to explore their intervention effects on the peroxidaseactivity of heme and hemoprotein. The main research includes the following twoaspects:(1) The effects of free tyrosine on hemohlobin-dependent redox reactionIn this chapter, we have examined the effects of free tyrosine, the mainendogenous phenol present in human blood plasma, and its analogues(3-chlorotyrosine, phenylalanine) on the redox active of hemoglobin and theformation of heme-to-protein cross-linking (Hb-X). The results showed that freetyrosine was an efficient reducing agent of ferryl species and also effective atpreventing the formation of cytotoxic Hb-X. Moreover, this amino acid couldefficiently inhibit Hb-H2O2-induced loss of HepG2cell viability, and lead to adose-dependent inhibition in Hb peroxidase activity-induced methylene blueoxidation. Meanwhile, the dimeric tyrosine was formed as the oxidation product oftyrosine during Hb redox reaction. Compared with free tyrosine,3-chlorotyrosine,an oxidation product of tyrosine and one of the proposed biomarker forhypochlorous acid (HOCl) in vivo, exhibited stronger antioxidant properties inHb-induced oxidative stress, which was consistent with its more efficient ability inthe reduction of ferryl Hb. These results showed that the presence of tyrosine andits derivative in vivo and vitro could ameliorate oxidative damage through ferrylheme reduction. The antioxidant ability, therefore, may provide new insights intothe nutritional and physiological significance of free tyrosine.(2) The effects of free histidine on heme peroxidase activityHistidine is one of several important amino acids in vivo, due to its ablity tocombine irons the histidine residues play a important role in maintaining thestructure and function of peroxidase. In this chapter, we examined the interventioneffects of free histidine on heme peroxidase activity. The results showed that, thecombination of histidine and heme iron could obviously promote the peroxidaseactivity of heme. In heme-Aβ complex peroxidase activity study, we found that, the increase of heme-Aβ complex peroxidase activity is dependent on the presence ofthe histidine residues in Aβ. The study also showed that the role of arginine in theheme peroxide cycle was not so important. These results indicate that both the freehistidine and the histidine residues in protein can promote the peroxide activity ofheme, therefore may provide new insights for histidine into the peroxidase activityof heme protein.