Tryptophan reduces creatine kinase activity in the brain cortex of rats.
Hypertryptophanemia is a rare inherited metabolic disorder probably caused by a blockage in the conversion of tryptophan to kynurenine, resulting in the accumulation of tryptophan and some of its metabolites in plasma and tissues of affected patients. The patients present mild-to-moderate mental retardation with exaggerated affective responses, periodic mood swings, and apparent hypersexual behavior. Creatine kinase plays a key role in energy metabolism of tissues with intermittently high and fluctuating energy requirements, such as nervous tissue. The main objective of the present study was to investigate the effect of acute administration of tryptophan on creatine kinase activity in brain cortex of Wistar rats. We also studied the in vitro effect of this amino acid on creatine kinase activity in the brain cortex of non-treated rats. The results indicated that tryptophan inhibits creatine kinase in vitro and in vivo. We also observed that the in vitro inhibition was fully prevented but not reversed by pre-incubation with reduced glutathione, suggesting that the inhibitory effect of tryptophan on CK activity is possibly mediated by oxidation of essential thiol groups of the enzyme and/or long-lasting adduct formation. Considering the importance of creatine kinase for the maintenance of energy homeostasis in the brain, it is conceivable that an inhibition of this enzyme activity in the brain may be one of the mechanisms by which tryptophan might be neurotoxic.
Cornelio
Andrea Renata
AR
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600, CEP 90.035-003, Porto Alegre, RS, Brazil.
Rodrigues
Valnês
V
de Souza Wyse
Angela Terezinha
AT
Dutra-Filho
Carlos Severo
CS
Wajner
Moacir
M
Wannmacher
Clovis Milton Duval
CM
D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology* / Q000503:physiopathology; D000818:Animals; D020739:Brain Diseases, Metabolic, Inborn / Q000201:enzymology* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D003402:Creatine Kinase / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005978:Glutathione / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014364:Tryptophan / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology
D014364:Tryptophan; D003402:Creatine Kinase; D005978:Glutathione