Kp. Braun et al., STABLE ACETALDEHYDE ADDUCTS - STRUCTURAL CHARACTERIZATION OF ACETALDEHYDE ADDUCTS OF HUMAN HEMOGLOBIN N-TERMINAL BETA-GLOBIN CHAIN PEPTIDES, Alcoholism, clinical and experimental research, 21(1), 1997, pp. 40-43
Acetaldehyde is the first oxidation product of ethanol in vivo. Our ea
rlier work showed that with sufficient acetaldehyde, five of the six p
ossible sites of the peptide pentalysine were modified as a Schiff bas
e (Braun KP, et al: J Biol Chem 270:11263-11266, 1995). However, we we
re unable to deduce unequivocally which site was unmodified. Lysine re
sidues, as well as the amine terminal valine residues, in hemoglobin h
ave been implicated as target structures for acetaldehyde adducts resu
lting from ethanol consumption. Hemoglobin adducts of acetaldehyde hav
e been used clinically as a marker of ethanol consumption, but the che
mical nature of these adducts remains undefined. As part of our contin
uing structural characterization of acetaldehyde-protein adduct format
ion, we studied the peptides Val-His-Leu-Thr-Pro and Val-His-Leu-Thr-P
ro-Val-Glu-Lys, from the amine terminus of the beta-globin chain of he
moglobin, in vitro. Both peptides have at least one potential site for
adduct formation. In the octapeptide, the N-terminal amine group of V
al as well as the epsilon-amine group of the lysine sidechain can pote
ntially be modified by acetaldehyde. We used mass spectrometry, carbon
-13 nuclear magnetic resonance, and Raman spectroscopy and characteriz
ed stable Schiff base acetaldehyde adducts of these two peptides at bo
th reactive sites. The identification of stable Schiff base adducts wi
th the N-terminal peptides of the beta-chain of hemoglobin as well as
with epsilon-amino groups of lysine provides another possible means of
monitoring ethanol consumption. The functional implications of these
stable Schiff bases remains undefined.