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 Hey 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 0.55 mM and 2.0 nmol Pi released per min per mg of protein, respectively. K-i value was approximately 0.1 mM, and the inhibition was of the non-competitive type. The results also showed a competition between Hey 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 Hey may be one of the mechanisms related to the neuronal dysfunction observed in human homocystinuria. (C) 2002 ISDN. Published by Elsevier Science Ltd. All rights reserved.