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

Abstract

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.

• Authors: Rodrigo Binkowski de Andrade, Tanise Gemelli, Denise Bertin Rojas, Cláudia Funchal, Carlos Severo Dutra-Filho, Clovis Milton Duval Wannmacher
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 364 Issue 1-2 Pg. 253-61 (May 2012) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 22311600 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• tyrosine methyl ester
• Tyrosine
• Tyrosine Transaminase
• Pyruvate Kinase
• Adenylate Kinase
• Glutathione
• Creatine

Topics

• Adenylate Kinase (metabolism)
• Animals
• Cerebral Cortex (metabolism, pathology)
• Creatine (pharmacology)
• Disease Models, Animal
• Energy Metabolism
• Enzyme Activation (drug effects)
• Glutathione (pharmacology)
• Humans
• Mitochondria (metabolism)
• Nervous System Diseases (metabolism, pathology)
• Pyruvate Kinase (metabolism)
• Rats
• Rats, Wistar
• Tyrosine (analogs & derivatives, deficiency, metabolism, pharmacology)
• Tyrosine Transaminase (metabolism)
• Tyrosinemias (metabolism, pathology)