Lipid peroxidation protein reactions with products

Protein cross-links may be also produced in reaction of 4-hydroxynonenal with lysine, histidine, serine, and cysteine residues, primarily via Michael addition (J5, R7, U8). These reactions occur spontaneously, but also may be catalyzed by certain glutatione 5-transferases. The glutathione transferase A4-4, which unlike other alpha-class glutathione transferases, shows high catalytic activity toward lipid peroxidation products such as 4-hydroxynon-2-enal, is the key enzyme for these reactions (B31). Products of protein coupling with aldehydes secondary to lipid peroxidation have a specific fluorescence, which can herald the protein oxidative modification process (CIO). 

The major aldehyde products of lipid peroxidation are malon-dialdehyde and 4-hydroxynonenal (Table 1, Fig. 4). Malondi-aldehyde can react with DNA to generate adducts at the bases A, C, and G. The mutagenic adduct MIG (pyrimido(l,2-a)purin-10(3H)one) has been detected at levels as high as 1 adduct per 10 nucleosides in human tissues. MIG is a reactive electrophile that can undergo further modification, leading to crosslinking of an adducted DNA strand to the opposite strand, or to some protein (22). Exocyclic etheno adducts can also arise from lipid peroxidation, possibly by reaction of an epoxide of 4-hydroxynonenal with A, C, or G in DNA. 

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