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Isokok

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IsoKs react covalently to lysyl residues of proteins to form a stable adduct and intramolecular cross-links (Iyer, Ghosh et al. 1989, Boutaud, Brame et al. 1999, Brame, Salomon et al. 1999). These molecules react at a rate that far exceeds other well studied products of lipid peroxidation, including 4-hydroxynonenal (4-HNE) (Brame, Salomon et al. 1999) (Fig. 1.3A). Results from in vitro oxidation of arachidonic acid strongly suggests that IsoKs form in vivo; however when tissues such as plasma and urine, IsoKs were not detected, although significant quantities of F2-IsoPs were detected by GC/MS. Analysis of iron/ADP/ascorbate treated liver microsomes also failed to detect any IsoKs, despite containing abundant F2-IsoPs. The reason for the failure to detect IsoKs in biological samples became apparent when studies were carried out to quantify the reactivity of IsoKs with proteins.…show more content…
1999). In contrast, when the same concentration of 4-hydroxynonenal (HNE) was incubated with the albumin, the levels of HNE declined at a slower rate than IsoK, taking approximately 80 minutes to deplete 50% of the free HNE, which is in range of previously published rates. These results strongly suggest that IsoK will only be found as an adduct on proteins and other amine-containing macromolecules. The initial reaction of isoketals with lysine forms pyrrole adducts that then mature under oxidizing conditions into lactam, hydroxylactam, or cross-linked adducts. Oxidation of protein pyrrole adducts in the immediate vicinity of other nucleophiles such as cysteines forms cross-links between the amino acid residues (Amarnath, Valentine et al.
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