The effects of the interactions between amino acids on pyruvate kinase activity from the brain cortex of young rats.
Considering that pyruvate kinase activity, a crucial enzyme for glucose metabolism and energy liberation in brain, may be regulated by some amino acids, it is possible that diminution of this enzyme activity may contribute to the brain damage caused by amino acids accumulated in metabolic diseases, such as phenylalanine, tryptophan and cystine. Therefore, the present study was undertaken to investigate the effect of these amino acids on pyruvate kinase activity in the brain cortex of rats. We also investigated the effect of serine and alanine on pyruvate kinase activity in the same tissue. The results suggested that phenylalanine, tryptophan, cystine, alanine, and serine act at the same site on the enzyme, phenylalanine, tryptophan, and cystine causing inhibition, and alanine and serine preventing this effect. Cystine also inhibited the enzyme activity through a different mechanism, possibly acting on the enzyme thiol groups. Considering that this enzyme is a target for amino acids accumulated in some metabolic diseases of amino acid metabolism, it is possible that its inhibition may contribute to the brain damage found in these diseases.
Feksa
Luciane Rosa
LR
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Rua Ramiro Barcelos 2600, CEP 90.035-003, Porto Alegre, RS, Brazil.
Cornelio
Andrea
A
Dutra-Filho
Carlos Severo
CS
Wyse
Angela Terezinha de Souza
AT
Wajner
Moacir
M
Wannmacher
Clovis Milton Duval
CM
D000592:Amino Acid Metabolism, Inborn Errors / Q000378:metabolism / Q000503:physiopathology; D000596:Amino Acids / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D020739:Brain Diseases, Metabolic, Inborn / Q000378:metabolism / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D003553:Cystine / Q000378:metabolism / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D010649:Phenylalanine / Q000378:metabolism / Q000494:pharmacology; D011770:Pyruvate Kinase / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012694:Serine / Q000378:metabolism / Q000494:pharmacology; D014364:Tryptophan / Q000378:metabolism / Q000494:pharmacology
D000596:Amino Acids; D012694:Serine; D010649:Phenylalanine; D003553:Cystine; D014364:Tryptophan; D011770:Pyruvate Kinase