Metabolism of ethyl methyl sulphide and sulphoxide in rat microsomal fractions

1. Gas chromatographic (GC) methods for the analysis of ethyl methyl sulphi de (EMS) and its corresponding sulphoxide (EMSO) and sulphone (EMSO2) in ra t microsomes and aspects of the in vitro metabolism of EMS and EMSO are des cribed. 2. EMS and the internal standard (dimethyl sulphide) were extracted by a he adspace procedure and separated satisfactorily using a column packed with 4 % Carbowax(R) 20 M/0.8% KOH on Carbopack(R) B. EMSO, EMSO2 and the internal standard n-propyl sulphone were separated satisfactorily using a 2-m colum n packed with 10% Carbowax(R) 20 M on Chromosorb(R) W. 3. Under the optimum conditions (incubation of 10 min and microsomal protei n content of similar to 4 mg/ml), 10% of the initial EMS concentration (2.5 mM) was converted to the corresponding sulphoxide in rat liver microsomal incubations. However, < 0.1% of the sulphone was detected when rat liver mi crosomes were incubated with EMS. Similarly, 2.5% of the initial EMSO conce ntration (2.5 mM) was converted to the corresponding sulphone by rat liver microsomes (similar to 4 mg/ml protein) during an incubation of 30 min. How ever, no EMS was detected after incubation with EMSO under these conditions . 4. The estimated apparent V-max and K-m for the sulphoxidation of EMS were 3.8+/-0.02 nmol/mg protein/min and 1.9+/-0.10 mM respectively. V-max1, V-ma x2 and K-m1 and K-m2 for the S-oxidation of EMSO were 0.5+/-0.01 and 0.2+/- 0.01nmol/mg protein/min and 0.7+/-0.02 and 0.1+/-0.00 mM respectively. 5. S tudies with selective inducers and inhibitors of microsomal monooxygenases indicated that the sulphoxidation of EMS is mediated mainly by FMO, whereas both FMO and cytochrome P450 are involved in the S-oxidation of EMSO.