BIOLOGICAL FATE OF AMINO-ACID, PEPTIDE AND PROTEIN HYDROPEROXIDES

In the course of searching for a suitable marker for studying protein oxidation, we have successfully elucidated the structures of three val ine hydroperoxides, i.e. beta-hydroperoxyvaline, which are novel produ cts of protein oxidation. The corresponding valine hydroxides were obt ained by sodium borohydride reduction [Fu, Hick, Sheil and Dean (1995) Free Rad. Biol. Med. 19, 281-292]. We hypothesized that valine hydrox ides might be the major biological degradation products of valine hydr operoxides and, as such, could be useful markers for the study of prot ein oxidation in vivo. The aim of this study was to investigate the fa te of valine hydroperoxide in selected biological systems by the use o f chemiluminescence detection of hydroperoxides and HPLC analysis of O -phthaldialdehyde derivatives of amino acid residues. The degradation of hydroperoxides present on gamma-radiolysed solutions of valine, Pro -Val-Gly, or BSA occurred in the presence of: (1) transition metals (F e2+, Fe3+, or CU2+), (2) the detoxifying enzyme GSH peroxidase, (3) hu man plasma, and (4) J774 mouse monocyte macrophage cells. The major de gradation product of valine hydroperoxide recovered in each case was f ound to be a valine hydroxide. These results suggest that valine hydro xide (derived from the hydroperoxide) may well be a useful in vivo mar ker for studying protein damage under oxidative stress.