Oxidative metabolism of propylthiouracil by peroxidases from rat bone marrow.
1. 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.
Lee
E
E
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Japan.
Miki
Y
Y
Hosokawa
M
M
Sayo
H
H
Kariya
K
K
D000818:Animals; D001853:Bone Marrow / Q000201:enzymology* / Q000378:metabolism; D047209:Eosinophil Peroxidase; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000302:isolation & purification*; D010544:Peroxidases / Q000302:isolation & purification*; D011189:Potassium Chloride / Q000494:pharmacology; D011441:Propylthiouracil / Q000493:pharmacokinetics*; D051381:Rats; D012973:Sodium Hypochlorite / Q000494:pharmacology
D011189:Potassium Chloride; D011441:Propylthiouracil; D012973:Sodium Hypochlorite; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D009195:Peroxidase