Protein adduction ketoaldehyde adducts

Brame, C.J., Salomon, R.G., Morrow, J.D., and Roberts, L.J. Identification of extremely reactive gamma-ketoaldehydes (isolevuglandins) as products of the isoprostane pathway and characterization of their lysyl protein adducts. J Biol Chem 274 (1999) 13139-13146. 

Davies, S.S., Amarnath, V., Brame, C.J., Boutaud, O., and Roberts, L.J. Measurement of chronic oxidative and inflammatory stress by quantification of isoketal/levuglandin gamma-ketoaldehyde protein adducts using liquid chromatography tandem mass spectrometry. Nat Pro toe 2 (2007) 2079-2091. 

Reactive aldehydes derived from lipid peroxidation, which are able to bind to several amino acid residues, are also capable of generating novel amino acid oxidation products. By means of specific polyclonal or monoclonal antibodies, the occurrence of malonaldehyde (MDA) and 4-hydroxynonenal (4-HNE) bound to cellular protein has been shown. Lysine modification by lipid peroxidation products (linoleic hydroperoxide) can yield neo-antigenic determinants such as N-c-hexanoyl lysine. Both histidine and lysine are nucleophilic amino acids and therefore vulnerable to modification by lipid peroxidation-derived electrophiles, such as 2-alkenals, 4-hydroxy-2-alkenals, and ketoaldehydes, derived from lipid peroxidation. Histidine shows specific reactivity toward 2-alkenals and 4-hydroxy-2-alkenals, whereas lysine is an ubiquitous target of aldehydes, generating various types of adducts. Covalent binding of reactive aldehydes to histidine and lysine is associated with the appearance of carbonyl reactivity and antigenicity of proteins [125]. 

How selective are pyridoxamine and lipophilic pyridoxamine analogs for scavenging y-ketoaldehydes compared to other reactive lipid peroxidation products The reactivity of pyridoxamine with a,p-unsaturated aldehydes is completely trivial, and pyridoxamine does not protect proteins from HNE adduction (Amarnath et ah, 2004 Davies et al., 2006). Pyridoxamine does react with a-ketoaldehydes such as methylglyoxal that form from the oxidative decomposition of carbohydrates and lipids (Voziyan et al., 2002), and these adducts can be detected in the mine of rodents fed pyridoxamine in their drinking water (Metz et... 

Subsequently, Amadori products may degrade irreversibly to a-ketoaldehyde compounds such as 1- and 3-deoxyglucosones, which may again react with proteins to form cross-links as well as fluorescent adducts called Maillard products (McLaughlin et al., 1980 Njorge et al., 1987 Monnier, 1989). 

---