Acute administration of l‐tyrosine alters energetic metabolism of hippocampus and striatum of infant rats

Abstract

Tyrosinemia type II is an inborn error of metabolism caused by mutations in the gene that encodes tyrosine aminotransferase, which leads to increased blood tyrosine levels. Considering that tyrosine levels are highly elevated in fluids of patients with tyrosinemia type II, and that previous studies demonstrated significant alterations in brain energy metabolism of young rats caused by l-tyrosine, the present study aimed to evaluate the effect of acute administration of l-tyrosine on the activities of citrate synthase, malate dehydrogenase, succinate dehydrogenase, and mitochondrial respiratory chain complexes I, II, II-III, and IV in posterior cortex, hippocampus, and striatum of infant rats. Wistar rats (10 days old) were killed 1h after a single intraperitoneal injection of tyrosine (500 mg/kg) or saline. The activities of energy metabolism enzymes were evaluated in brain of rats. Our results demonstrated that acute administration of l-tyrosine inhibited the activity of citrate synthase activity in striatum and increased the activities of malate dehydrogenase and succinate dehydrogenase in hippocampus. On the other hand, these enzymes were not affected in posterior cortex. The activities of complex I and complex II were inhibited by acute administration of l-tyrosine in striatum. On the other hand, the acute administration of l-tyrosine increased the activity of activity of complex II-III in hippocampus. Complex IV was not affected by acute administration of l-tyrosine in infant rats. Our results indicate an alteration in the energy metabolism in hippocampus and striatum of infant rats after acute administration of l-tyrosine. If the same effects occur in the brain of the patients, it is possible that energy metabolism impairment may be contribute to possible damage in memory and cognitive processes in patients with tyrosinemia type II.

Analysis of the metabolic pathways affected by hot-Humid or dry climate based on fecal metabolomics coupled with serum metabolic changes in broiler chickens

“…In addition, tyrosine is a synthetic precursor of hormones, thyroids, and colorants (melanin) [48]. It can also be converted into dopamine or catecholamine for signal transduction, or it can form a protein activating enzyme with a phosphate group, regulate the activity of the enzyme, and provide energy [49,50,51]. The catabolism of tyrosine involves the enzymatic, energy metabolism of the Krebs cycle.…”

Neurological and Neuropsychological Problems in Tyrosinemia Type I Patients

“…Increased brain tyrosine concentrations can, in turn, lead to a direct toxic effect of tyrosine in the brain like phenylalanine has in PKU (van Spronsen et al 2009;Surtees and Blau 2000). Research on the toxicity of tyrosine showed that increased tyrosine concentrations can induce all kinds of processes including oxidative stress and DNA repair issues, with, as a potential consequence, brain dysfunction (De Pra et al 2014;Macedo et al 2013;Ramos et al 2013), but the exact tyrosine concentration that harms development still needs to be established.…”