Interaction of lysinoalanine with the protein synthesizing apparatus

Lysinoalanine N epsilon-(DL-2-amino-2-carboxyethyl)-L-lysine; LAL], a nephrotoxic lysine analog, inhibits the lysyl-tRNA-synthetase (EC 6.1.1.6) of prokaryotic and eukaryotic cells competitively at micromolar concentrations. Incorporation of 14C]lysine into protein by a cell-free eukaryotic protein-synthesizing system was inhibited by LAL. Inhibition was 69.7% and 18.4% at LAL concentrations of 1.0 mM and 0.1 mM, respectively. LAL was incorporated into protein as well as being an inhibitor as indicated by the incorporation of 14C]LAL into protein by the cell-free eukaryote protein-synthesizing system. The proteins labeled with 14C]LAL co-electrophoresed with those labeled with 14C]lysine. These results indicate that LAL is an inhibitor of both prokaryote and eukaryote lysyl-tRNA-synthetase. Furthermore, it is incorporated into protein. Both of these actions can be factors in the nephrotoxicity of this common food contaminant. Possible mechanisms for the toxicity of lysinoalanine are discussed.