The formation and stability of imidazolidinone adducts from acetaldehyde and model peptides. A kinetic study with implications for protein modification in alcohol abuse.
The kinetics of the reaction of acetaldehyde (AcH) with the alpha-amino group of several di- and tripeptides to form 2-methylimidazolidin-4-one adducts were determined at pH 7, 4, 37 degrees 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 microm; [free peptide alpha-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 degrees C. Extrapolation of an Arrhenius plot to 37 degrees C provided an estimate of K(obs) of 0.002 h-1 (t1/2 approximately 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.
Fowles
L F
LF
Alcohol Research Unit, Department of Biochemistry, University of Queensland, Australia.
Beck
E
E
Worrall
S
S
Shanley
B C
BC
de Jersey
J
J
D000079:Acetaldehyde / Q000737:chemistry*; D004355:Drug Stability; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology*; D007700:Kinetics; D010455:Peptides / Q000737:chemistry*; D013696:Temperature; D013997:Time Factors
D007093:Imidazoles; D010455:Peptides; D000079:Acetaldehyde