丙硫氧嘧啶在大鼠骨髓过氧化物酶作用下的氧化代谢

Oxidative metabolism of propylthiouracil by peroxidases from rat bone marrow.

Lee E, Miki Y, Hosokawa M, Sayo H, Kariya K

Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Japan.

Xenobiotica. 1988 Oct;18(10):1135-42. doi: 10.3109/00498258809042236.

Abstract

Propylthiouracil (PTU) was degraded by myeloperoxidase (MPO) or eosinophil peroxidase (EPO), purified from rat bone marrow, in the presence of H2O2 and Cl-. In the absence of either H2O2 or Cl-, MPO and EPO do not degrade PTU. Optimum concentrations of KCl for MPO and EPO were 50 and 250 mM, respectively. 2. The characteristics of PTU degradation by MPO-H2O2-Cl- were similar to those of the chlorinating activity of the peroxidase. 3. Hypochlorous acid as well as MPO-H2O2-Cl- also degraded PTU. Metabolites of PTU degradation by MPO-H2O2-Cl-, which were separated by C18 reversed phase h.p.l.c., were the same as those produced by hypochlorous acid. 4. Of the metabolites of PTU formed by MPO-H2O2-Cl-, one was identified as PTU sulphonic acid (6-propyl-4-hydroxypyrimidine-2-sulphonate) and another seemed to be propyluracil.

摘要

丙硫氧嘧啶（PTU）在过氧化氢（H₂O₂）和氯离子（Cl⁻）存在的情况下，被从大鼠骨髓中纯化得到的髓过氧化物酶（MPO）或嗜酸性粒细胞过氧化物酶（EPO）降解。在没有H₂O₂或Cl⁻的情况下，MPO和EPO不会降解PTU。MPO和EPO的氯化钾最佳浓度分别为50 mM和250 mM。2. MPO-H₂O₂-Cl⁻对PTU的降解特性与过氧化物酶的氯化活性相似。3. 次氯酸以及MPO-H₂O₂-Cl⁻也能降解PTU。通过C18反相高效液相色谱法分离的MPO-H₂O₂-Cl⁻降解PTU的代谢产物与次氯酸产生的代谢产物相同。4. 在MPO-H₂O₂-Cl⁻形成的PTU代谢产物中，一种被鉴定为PTU磺酸（6-丙基-4-羟基嘧啶-2-磺酸盐），另一种似乎是丙基尿嘧啶。