Tyrosine impairs enzymes of energy metabolism in cerebral cortex of rats.

Tyrosine levels are abnormally elevated in tissues and physiological fluids of patients with inborn errors of tyrosine catabolism, especially in tyrosinemia type II, which is caused by deficiency of tyrosine aminotransferase and provokes eyes, skin, and central nervous system disturbances. Considering that the mechanisms of brain damage in these disorders are poorly known, in this study, we investigated the in vivo and in vitro effects of tyrosine on some parameters of energy metabolism in cerebral cortex of 14-day-old Wistar rats. We observed that 2 mM tyrosine inhibited in vitro the pyruvate kinase (PK) activity and that this inhibition was prevented by 1 mM reduced glutathione with 30, 60, and 90 min of preincubation. Moreover, administration of tyrosine methyl ester (TME) (0.5 mg/g of body weight) decreased the activity of PK and this reduction was prevented by pre-treatment with creatine (Cr). On the other hand, tyrosine did not alter adenylate kinase (AK) activity in vitro, but administration of TME enhanced AK activity not prevented by Cr pre-treatment. Finally, TME administration decreased the activity of CK from cytosolic and mitochondrial fractions and this diminution was prevented by Cr pre-treatment. The results suggest that tyrosine alters essential sulfhydryl groups necessary for CK and PK functions, possibly through oxidative stress. In case this also occurs in the patients, it is possible that energy metabolism alterations may contribute, along with other mechanisms, to the neurological dysfunction of hypertyrosinemias.

Crisis neurológica en Tirosinemia hereditaria / Neurological crisis in hereditary Tyrosinaemia

La Tirosinemia tipo I es el resultado de un error innato en la etapa final del metabolismo de la Tirosina. Sus manifestaciones clínicas son variables, las cuales pueden verse agravadas con la aparición de crisis neurológica. El objetivo del presente trabajo es reportar el caso de una preescolar portadora de la enfermedad, que desarrolló parálisis fláccida asociada a insuficiencia respiratoria y que requirió conexión a ventilación mecánica.

Behavioural effects of acute phenylalanine and tyrosine depletion in healthy male volunteers.

Acute phenylalanine and tyrosine depletion (APTD) studies have been used to assess the role of the cathecholaminergic system in various aspects of human behaviour. In this study we conducted a randomized, double-blind, controlled and cross-over comparison to evaluate the effects of APTD on memory, attention and mood in normal subjects. Twelve healthy male volunteers were included in this study. The subjects ingested a nutritionally balanced mixture (B) or a similar mixture deficient in phenylalanine and tyrosine (PT-). Before and 5 h after ingestion of the drink, volunteers underwent tests on mood, memory and attention. Results of the memory tests showed that PT- mixture impaired word recall as measured in Rey's test (p = 0.016). The assessment of changes in mood showed that the balanced mixture improved scores of as alertness (VAMS factor I, p = 0.037) and the PT- mixture induces an opposite effect, increased scores of anxiety (Profiles of Mental State composed-anxious dimension, p = 0.022). These results suggest that tyrosine plasma levels and cathecholamines may be important factors in regulating mood and memory.