Nutritional and Toxicological Assessment of an N6-Diethylphospholysyl Peptide: A Synthetic Compound Resembling the Covalently Bound Metabolite of an Organophosphate Pesticide to Protein-Bound Lysine

Abstract

A 1- and 5-week mouse growth study was conducted to evaluate the potential toxicological implications and nutritional value of a phosphorylated peptide, Ac-Ala-Lys(PO3Et2)-Val-OEt (a synthetic model resembling the covalently attached metabolite of organophosphate pesticide to protein-bound lysine), and the nonphosphorylated peptide Ac-Ala-Lys-Val-OEt. A basal diet, adequate in all nutrients except lysine (0.26%), was supplemented with 1 and 2% of the phosphorylated or the nonphosphorylated peptide, and with the amounts of crystalline lysine equivalent to those provided by the peptides. Relative lysine bioavailability was calculated by comparing growth of mice fed a peptide diet with that of mice fed basal plus an equivalent amount of crystalline lysine. Values for relative bioavailability of lysine (l-lysine = 100) in the phosphorylated peptide after 1 or 5 weeks of test were zero. Values for relative bioavailability of lysine in the nonphosphorylated peptide were, however, 100 and 86−99% after 1 and 5 weeks of test, respectively. The addition of the peptides had no significant adverse effects on relative mouse organ weights or most blood hematology parameters. Keywords: Phosphorylation; protein-bound lysine; N6-diethylphospholysine; organophosphate pesticides; model peptides; mouse growth, organ weights; blood hematology; lysine bioavailability