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.
Lifsey
B J
BJ
Program in Environmental Toxicology, University of Tennessee College of Veterinary Medicine, Knoxville 37901.
Farkas
W R
WR
Reyniers
J P
JP
D000604:Amino Acyl-tRNA Synthetases / Q000037:antagonists & inhibitors*; D000818:Animals; D001667:Binding, Competitive; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D008250:Lysine-tRNA Ligase / Q000037:antagonists & inhibitors*; D008241:Lysinoalanine / Q000378:metabolism / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects; D011817:Rabbits
D008241:Lysinoalanine; D000604:Amino Acyl-tRNA Synthetases; D008250:Lysine-tRNA Ligase; D008239:Lysine