Interaction of lysinoalanine with the protein synthesizing apparatus

• Published in: Chemico-biological interactions Vol. 68; no. 3-4; p. 241
• Main Authors: Lifsey, Jr, B J, Farkas, W R, Reyniers, J P
• Format: Journal Article
• Language: English
• Published: Ireland 1988
• Subjects: Amino Acyl-tRNA Synthetases - antagonists & inhibitors; Animals; Binding, Competitive; Electrophoresis, Polyacrylamide Gel; Escherichia coli - enzymology; Liver - enzymology; Lysine - analogs & derivatives; Lysine - metabolism; Lysine-tRNA Ligase - antagonists & inhibitors; Lysinoalanine - metabolism; Lysinoalanine - pharmacology; Protein Biosynthesis - drug effects; Rabbits
• ISSN: 0009-2797
• DOI: 10.1016/0009-2797(88)90019-1

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.