Is hemoglobin a catalyst for sulfoxidation of chlorpromazine? An investigation with isolated purified hemoglobin and hemoglobin in monooxygenase and peroxidase mimicking systems.

The possible role of hemoglobin in the sulfoxidation of chlorpromazine is still a controversial subject. Therefore this sulfoxidation was investigated with purified oxyhemoglobin and methemoglobin under various conditions: (i) in phosphate buffer pH 6.5; (ii) in monooxygenase mimicking systems with electron donors like ascorbic acid and NADPH, the last, with and without an electron carrier like methylene blue and cytochrome c reductase; (iii) in the presence of H2O2. Only in the presence of H2O2 chlorpromazine was converted into chlorpromazine sulfoxide in a considerable amount. This so-called peroxidase activity of hemoglobin appeared not to be based on a Fenton-type reaction. An oxidized reactive form of hemoglobin (i.e. ferrylhemoglobin) is responsible for the sulfoxidation. In the other systems only with ascorbic acid some chlorpromazine sulfoxide was produced. This is probably due to the production of H2O2 and the subsequent peroxidase activity of hemoglobin. Chlorpromazine enhanced the autoxidation of oxyhemoglobin, without being transformed itself.