On the mechanism of the inhibition of Na(+), K(+)-ATPase activity caused by homocysteine.
In the present work, we investigated the kinetics of the inhibition of Na(+), K(+)-ATPase activity caused by homocysteine (Hcy) in rat hippocampus. We also studied the interaction between Hcy and phenylalanine (Phe) and the kinetics of alanine (Ala) reversal of the inhibition of Na(+), K(+)-ATPase caused by Hcy. The apparent K(m) and V(max) of Na(+), K(+)-ATPase for ATP as substrate were 0.55mM and 2.0nmol Pi released per min per mg of protein, respectively. K(i) value was approximately 0.1mM, and the inhibition was of the non-competitive type. The results also showed a competition between Hcy and Phe. Ala per se did not alter this enzyme, but prevented the inhibitory effect caused by Hcy, suggesting a common binding site for these substances. It is proposed that the inhibition of Na(+), K(+)-ATPase by Hcy may be one of the mechanisms related to the neuronal dysfunction observed in human homocystinuria.
Streck
Emilio L
EL
Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP, 90035-003 Porto Alegre, RS, Brazil.
Zugno
Alexandra I
AI
Tagliari
Bárbara
B
Sarkis
João J F
JJ
Wajner
Moacir
M
Wannmacher
Clóvis M D
CM
Wyse
Angela T S
AT
D000409:Alanine / Q000378:metabolism; D000818:Animals; D006624:Hippocampus / Q000378:metabolism*; D006710:Homocysteine / Q000378:metabolism*; D007700:Kinetics; D010649:Phenylalanine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D006710:Homocysteine; D010649:Phenylalanine; D000254:Sodium-Potassium-Exchanging ATPase; D000409:Alanine