Roles of the tyrosine isomers meta- tyrosine and ortho- tyrosine in oxidative stress

Abstract

The damage to cellular components by reactive oxygen species, termed oxidative stress, both increases with age and likely contributes to age-related diseases including Alzheimer’s disease, atherosclerosis, diabetes, and cataract formation. In the setting of oxidative stress, hydroxyl radicals can oxidize the benzyl ring of the amino acid phenylalanine, which then produces the abnormal tyrosine isomers meta-tyrosine or ortho-tyrosine. While elevations in m-tyrosine and o-tyrosine concentrations have been used as a biological marker of oxidative stress, there is emerging evidence from bacterial, plant, and mammalian studies demonstrating that these isomers, particularly m-tyrosine, directly produce adverse effects to cells and tissues. These new findings suggest that the abnormal tyrosine isomers could in fact represent mediators of the effects of oxidative stress. Consequently the accumulation of m- and o-tyrosine may disrupt cellular homeostasis and contribute to disease pathogenesis, and as result, effective defenses against oxidative stress can encompass not only the elimination of reactive oxygen species but also the metabolism and ultimately the removal of the abnormal tyrosine isomers from the cellular amino acid pool. Future research in this area is needed to clarify the biologic mechanisms by which the tyrosine isomers damage cells and disrupt the function of tissues and organs, and to identify the metabolic pathways involved in removing the accumulated isomers after exposure to oxidative stress.

The Phytotoxicity of Meta-Tyrosine Is Associated With Altered Phenylalanine Metabolism and Misincorporation of This Non-Proteinogenic Phe-Analog to the Plant's Proteome

“…Our data provide further insights into m-tyrosine-mediated phytotoxicity. Under different conditions, and more particularly under oxidative stress, m-tyrosine is accumulating to higher levels in the cell (Ipson and Fisher, 2016). m-tyrosine is directly generated by hydroxyl radical attack of phenylalanine when levels of reactive oxygen species are elevated (Rodgers and Shiozawa, 2008), or might be produced enzymatically, as indicated in a few plant species (Mothes et al, 1964;Bertin et al, 2007;Huang et al, 2012).…”

Hydrogen produced in rat colon improves in vivo reduction–oxidation balance due to induced regeneration of α-tocopherol

“…In the present work, to assess the effect of colonic H 2 on hydroxyl radicals, we used instead tyrosine isomers as in vivo markers for hydroxyl radical detection. Although p-tyrosine is produced by phenylalanine hydroxylase in vivo, hydroxyl radicals randomly attack the aromatic ring of phenylalanine at different positions, resulting in production of m-and o-tyrosine in addition to p-tyrosine (35) . Using the same marker, the hydroxyl radical scavenging activity of certain antioxidative compounds has been evaluated in rats (36) and humans (37) .…”

Time-course analysis ofStreptococcus sanguinisafter manganese depletion reveals changes in glycolytic, nucleotide, and redox metabolites

“…Since the air flow was kept constant throughout the experiment, we expected that GSH would have been utilized by redox enzymes for ROS remediation. While ROS levels were not measured directly by the metabolomics analysis, levels of ortho-tyrosine increased (Figure 5c), which is an indicator of high ROS states (Ipson and Fisher, 2016;Matayatsuk et al, 2007). Thus, the accumulation of GSH is probably due to Mn depletion, either because of a blockage of GSH utilization by redox enzymes or due to a reduction of…”