Lorrai Anita, Padiglia Alessandra, Medda Rosaria, Bellelli Andrea, Arcovito Alessandro, Floris Giovanni
Department of Sciences Applied to Biosystems, University of Cagliari, Italy.
J Protein Chem. 2002 Feb;21(2):97-104. doi: 10.1023/a:1014524227764.
The kinetics of the catalytic cycle of myeloperoxidase and of horseradish peroxidase reacting with aminoglycosides have been studied by conventional and stopped-flow spectrophotometry. Aminoglycosides acted as one-electron reducing substrates converting compound I, formed when stoichiometric amounts of hydrogen peroxide were added to the enzyme, to compound II, and compound II to the resting, ferric enzyme. The latter gradually decayed into a further spectroscopic derivative (lambda(max) = 540 and 403 nm) tentatively identified as a complex of ferric heme with the antibiotic oxidation product(s), and the resulting enzyme was fully inactivated. Since myeloperoxidase is the only human enzyme known to convert chloride ions into the cytotoxic hypochlorous acid, the data presented in this paper bear relevance to the pharmacological effects of aminoglycoside antibiotics, which, while inhibiting bacterial growth, also prevent oxidative cellular damage caused by hypochlorous acid aging as substrates and inhibitors of myeloperoxidase.
通过传统分光光度法和停流分光光度法研究了髓过氧化物酶和辣根过氧化物酶与氨基糖苷类反应的催化循环动力学。氨基糖苷类作为单电子还原底物，将在向酶中加入化学计量的过氧化氢时形成的化合物I转化为化合物II，并将化合物II转化为静止的铁酶。后者逐渐衰变为另一种光谱衍生物（最大吸收波长 = 540和403 nm），初步鉴定为铁血红素与抗生素氧化产物的复合物，并且所得酶完全失活。由于髓过氧化物酶是已知唯一能将氯离子转化为细胞毒性次氯酸的人类酶，本文提供的数据与氨基糖苷类抗生素的药理作用相关，氨基糖苷类抗生素在抑制细菌生长的同时，还作为髓过氧化物酶的底物和抑制剂，防止次氯酸老化引起的氧化细胞损伤。
