Degradation and oxidation of methionine enkephalin by human neutrophils.
Met5-enkephalin, tyr-gly-phe-met, is an endogenous pentapeptide, with morphine agonist activity. In this study, we demonstrated that met5-enkephalin was degraded with the release of tyrosine by resting human PMN, whereas it was degraded as well as oxidized to its sulfoxide derivative, met5-(O)-enkephalin, by phagocytosing PMN. PMN also degraded met5-(O)-enkephalin but to a lesser extent. Bacitracin at 1 gm/L inhibited the degradation and oxidation of met5-enkephalin without affecting the production of superoxide and viability of PMN. The oxidation of met5-enkephalin by phagocytosing PMN was inhibited by catalase or NaN3 but not by SOD. This suggests that the oxidation of met5-enkephalin by phagocytosing PMN was, at least in part, dependent on the MPO system (MPO-H2O2-halide). Using purified canine MPO, we further demonstrated that MPO-H2O2-CI- oxidized met5-enkephalin to met5-(O)-enkephalin. The MPO-mediated oxidation of met5-enkephalin was inhibited by methionine but not by methionine sulfoxide, tyrosine, glycine, or phenylalanine, confirming that it was the methionine moiety of met5-enkephalin which was oxidized. Since both the sulfoxide derivative and the degradation products met5-enkephalin have reduced opiate agonist activity, oxidation and degradation of met5-enkephalin by PMN may contribute to the pain at the site of inflammation. (J Lab Clin Med 99:418, 1982.)
D001386:Azides / Q000494:pharmacology; D001711:Biotransformation; D002374:Catalase / Q000494:pharmacology; D004723:Endorphins / Q000097:blood*; D004744:Enkephalin, Methionine; D004745:Enkephalins / Q000097:blood*; D006801:Humans; D066298:In Vitro Techniques; D009504:Neutrophils / Q000378:metabolism*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000302:isolation & purification
D001386:Azides; D004723:Endorphins; D004745:Enkephalins; D013481:Superoxides; D014443:Tyrosine; D004744:Enkephalin, Methionine; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase