The formation and stability of imidazolidinone adducts from acetaldehyde and model peptides: A kinetic study with implications for protein modification in alcohol abuse

Abstract

The kinetics of the reaction of acetaldehyde (AcH) with the α-amino group of several di- and tripeptides to form 2-methylimidazolidin-4-one adducts were determined at pH 7,4, 37°C, using reverse phase HPLC to separate peptides from adducts. The imidazolidin-4-one structure of the adducts was confirmed by 13C NMR spectroscopy. The reaction of val-gly-gly with AcH was shown to follow second-order kinetics over a wide range of concentrations of both reactants, with k2 = 0.734 ± 0.032 M-1 min-1. Under conditions similar to those in the liver of an alcoholic during chronic ethanol oxidation ([AcH]o = 50-910 μM; [free peptide α-amino groups]o = 1.5 mM), the reaction proceeded until effectively all of the AcH had been consumed. The side chain of the N-terminal amino acid was shown not to have a marked effect on the rate of imidazolidinone formation. The decomposition of the imidazolidinone adduct of val-gly-gly and AcH was observed at 60-100°C. Extrapolation of an Arrhenius plot to 37°C provided an estimate of kobs of 0.002 h-1 (t1/2 ∼ 14 days). Based on these kinetic studies, it is concluded that imidazolidinone adducts of AcH with proteins may be present in the liver and, possibly, in the blood of alcoholics.