Lysine residues in
proteins undergo multiple enzymatic and nonenzymatic
post-translational modifications (PTMs). The terminal ε amine
group of lysine residues in proteins is carbonylated chemically by
carbonyl species such as glyoxal (GO; OCH–CHO, C2H2O2; MW 58) and methylglyoxal (MGO; OCH-C(=O)–CH3, C3H4O2; MW 72) that are
derived from the metabolism of endogenous substances including glucose.
The dicarbonyl species malondialdehyde (MDA, OCH–CH2–CHO, C3H4O2; MW 72) is generated
by enzymatic and nonenzymatic peroxidation of polyunsaturated fatty
acids (PUFAs). GO, MGO, and MDA occur in biological systems in their
free forms and in their conjugated forms adducted to free amino acids
and amino acid residues in proteins, notably to lysine. MDA is a C–H-acidic
acid (pKa, 4.45). Biological MDA is widely
used as a biomarker of lipid peroxidation. The most frequently analyzed
biological samples for MDA are plasma and serum. Reportedly, MDA concentrations
in plasma and serum samples of healthy and ill humans range by several
orders of magnitude. The most severe preanalytical contributor is
artificial formation of MDA in lipid-rich samples such as plasma and
serum. In very few publications, plasma MDA concentrations were reported
to lie in the lower mM-range.