Inhibition of Na+, K+-ATPase activity in rat striatum by guanidinoacetate

The aim of this work was to investigate the effect of guanidinoacetate (GAA), the principal metabolite accumulating in guanidinoacetate methyltransferase (GAMT)-deficiency, on Na+, K+-ATPase, Mg2+-ATPase and acetylcholinesterase (AChE) activities in striatum of young rats. We also studied the kinetics of the inhibition of Na+, K+-ATPase activity caused by guanidinoacetate. Guanidinoacetate did not alter acetylcholinesterase and Mg2+-ATPase activities, but significantly inhibited Na+, K+-ATPase activity. The apparent Km and V-max of Na+, K+-ATPase for ATP as substrate were 0.20 mM and 0.82 nmol inorganic phosphate (Pi) released per min per mg of protein, respectively. K-i value was 7.18 mM, and the inhibition was of the uncompetitive type. The results also showed a competition between guanidinoacetate and argininic acid (AA), suggesting a common binding site for the guanidino compounds (GC) on the enzyme. It is proposed that Na+, K+-ATPase inhibition by guanidinoacetate may be one of the mechanisms involved in the neuronal dysfunction observed in GAMT-deficiency and in other diseases which accumulate guanidinoacetate. (C) 2003 ISDN. Published by Elsevier Science Ltd. All rights reserved.