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.
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, UFRGS, Rua Ramiro Barcelos 2600-Anexo, Porto Alegre, RS 90035-003, Brazil.
Rodrigo Binkowski
RB
de Andrade
Tanise
T
Gemelli
Denise Bertin
DB
Rojas
Cláudia
C
Funchal
Carlos Severo
CS
Dutra-Filho
Clovis Milton Duval
CM
Wannmacher
D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D003401:Creatine / Q000494:pharmacology; D004195:Disease Models, Animal; D004734:Energy Metabolism; D004789:Enzyme Activation / Q000187:drug effects*; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009422:Nervous System Diseases / Q000378:metabolism* / Q000473:pathology; D011770:Pyruvate Kinase / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000031:analogs & derivatives / Q000172:deficiency / Q000378:metabolism* / Q000494:pharmacology; D014444:Tyrosine Transaminase / Q000378:metabolism; D020176:Tyrosinemias / Q000378:metabolism* / Q000473:pathology
C040444:tyrosine methyl ester; D014443:Tyrosine; D014444:Tyrosine Transaminase; D011770:Pyruvate Kinase; D000263:Adenylate Kinase; D005978:Glutathione; D003401:Creatine