Malondialdehyde-Induced Post-Translational Modification of Human Hemoglobin

Abstract

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 (pK a, 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.

Accumulation of Renal Fibrosis in Hyperuricemia Rats Is Attributed to the Recruitment of Mast Cells, Activation of the TGF-β1/Smad2/3 Pathway, and Aggravation of Oxidative Stress

“…Lipid peroxides, including malondialdehyde (MDA), are formed when the body resists oxidative stress through enzymatic or non-enzymatic systems. The level of MDA indirectly reflects the severity of the oxidative attack on the body [ 38 ]. Levels of SOD, GSH-Px, and glutathione reductase (GR) are often considered indicators of the body’s antioxidant capacity, mainly because SOD converts superoxide into hydrogen peroxide [ 39 ].…”

Circulating and Urinary Concentrations of Malondialdehyde in Aging Humans in Health and Disease: Review and Discussion

“…Simplified scheme showing the chemical structures of arachidonic acid, a polyunsaturated fatty acid, which is peroxidized with chemicals and enzymes such as cyclooxygenase, to finally generate 4-hydroxy-2-nonenal and malondialdehyde (MDA) in its free form. MDA also occurs as a conjugate with the terminal amine group (N ε ) of L-lysine residues in proteins, such as albumin and hemoglobin [3]. 12-Hydroxy-5,8,10-heptadecatrienoic acid and thromboxane A 2 (not shown) are also metabolites of arachidonic acid peroxidation [1].…”