Turkall R M, Denison R C, Tsan M F
J Lab Clin Med. 1982 Mar;99(3):418-27.
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.)
甲硫氨酸脑啡肽，酪氨酰-甘氨酰-苯丙氨酰-甲硫氨酸，是一种内源性五肽，具有吗啡激动剂活性。在本研究中，我们证明静息的人中性粒细胞可使甲硫氨酸脑啡肽降解并释放出酪氨酸，而吞噬状态的中性粒细胞不仅可使甲硫氨酸脑啡肽降解，还可将其氧化为亚砜衍生物甲硫氨酸-（O）-脑啡肽。中性粒细胞也可降解甲硫氨酸-（O）-脑啡肽，但程度较轻。1g/L的杆菌肽可抑制甲硫氨酸脑啡肽的降解和氧化，而不影响超氧化物的产生及中性粒细胞的活力。吞噬状态的中性粒细胞对甲硫氨酸脑啡肽的氧化作用可被过氧化氢酶或叠氮化钠抑制，但不被超氧化物歧化酶抑制。这表明吞噬状态的中性粒细胞对甲硫氨酸脑啡肽的氧化作用至少部分依赖于髓过氧化物酶系统（髓过氧化物酶-H₂O₂-卤化物）。使用纯化的犬髓过氧化物酶，我们进一步证明髓过氧化物酶-H₂O₂-Cl⁻可将甲硫氨酸脑啡肽氧化为甲硫氨酸-（O）-脑啡肽。髓过氧化物酶介导的甲硫氨酸脑啡肽氧化作用可被甲硫氨酸抑制，但不被甲硫氨酸亚砜、酪氨酸、甘氨酸或苯丙氨酸抑制，这证实被氧化的是甲硫氨酸脑啡肽的甲硫氨酸部分。由于亚砜衍生物和降解产物甲硫氨酸脑啡肽的阿片激动剂活性均降低，中性粒细胞对甲硫氨酸脑啡肽的氧化和降解可能会导致炎症部位的疼痛。（《实验室与临床医学杂志》99:418，1982年）
