Tyrosine aminotransferase is involved in the oxidative stress response by metabolizing tyrosine in .

Under oxidative stress conditions, hydroxyl radicals can oxidize the phenyl ring of phenylalanine, producing the abnormal tyrosine isomer tyrosine (-tyrosine). Tyrosine levels are commonly used as a biomarker of oxidative stress, and its accumulation has recently been reported to adversely affect cells, suggesting a direct role for tyrosine in oxidative stress effects. We found that the ortholog of tyrosine aminotransferase (TATN-1)-the first enzyme involved in the metabolic degradation of tyrosine-is up-regulated in response to oxidative stress and directly activated by the oxidative stress-responsive transcription factor SKN-1. Worms deficient in tyrosine aminotransferase activity displayed increased sensitivity to multiple sources of oxidative stress. Biochemical assays revealed that tyrosine is a substrate for TATN-1-mediated deamination, suggesting that TATN-1 also metabolizes tyrosine. Consistent with a toxic effect of -tyrosine and a protective function of TATN-1, mutant worms exhibited delayed development, marked reduction in fertility, and shortened lifespan when exposed to -tyrosine. A forward genetic screen identified a mutation in the previously uncharacterized gene -homologous with human transcription factor 20 (TCF20) and retinoic acid-induced 1 (RAI1)-that suppresses the adverse phenotypes observed in -tyrosine-treated mutant worms. RNA-Seq analysis of mutant worms disclosed a significant reduction in the expression of specific isoforms of genes encoding ribosomal proteins, suggesting that alterations in protein synthesis or ribosome structure could diminish the adverse effects of -tyrosine. Our findings uncover a critical role for tyrosine aminotransferase in the oxidative stress response via tyrosine metabolism.