Hyperargininemia is a metabolic disorder biochemically characterized by tissue accumulation of
arginine (Arg) and other guanidino compounds (GC). Convulsions,
lethargy and psychomotor delay are predominant clinical features of this disease. Considering that some GC are epileptogenic and cause a decrease in membrane fluidity and that Na+,K(+)-
ATPase, a membrane-bound
enzyme, is essential for cellular excitability and is decreased in experimental and human
epilepsy, in the present study we determined the in vitro effects of Arg, N-acetylarginine (NAA),
argininic acid (AA) and
homoarginine (HA) on the activity of Na+,K(+)-
ATPase in the synaptic plasma membrane from cerebral cortex of young rats in the hope to identify a possible mechanism for the brain damage in
hyperargininemia. The results showed that all GC tested, except Arg, significantly inhibited Na+,K(+)-
ATPase activity at concentrations similar to those observed in plasma and CSF of patients with
hyperargininemia. In addition, competition between NAA, AA and HA for the binding to the
enzyme was observed, suggesting a common binding site for the GC. It is therefore possible that the inhibitory effect of GC on Na+,K(+)-
ATPase may be related to the brain dysfunction observed in
hyperargininemia.