The effect of thionamides and related compounds on trimethylamine oxidase activity in hepatic microsomes isolated from chickens (Gallus domesticus).
1. Thiourea, ethylene thiourea, methimazole and (+) 5-vinyl-oxazolidine-2-thione (OZT) gave similar inhibition curves when added to the reaction mixture. A concentration of 20 microM reduced the activity by over 75%. Thioacetamide and thiobenzamide also behaved as potent inhibitors. 2. (-) OZT had less effect than the (+) isomer. 3. Microsomes from chickens with an inherently low capacity for synthesising TMA oxidase and enhanced susceptibility to the goitrogenic effects of OZT were more sensitive to this inhibition than those from a high TMA oxidase strain. 4. Inhibition by thiourea was competitive and the apparent K1 for low oxidase microsomes was 2.5 x 10(-6)M. 5. The inhibitory property of thionamides was lost when the S atom was replaced by O but was retained when it was oxidised to the sulphinic acid or sulphoxide. 6. Incubation of microsomes with sodium diethyldithiocarbamate reduced their TMA oxidase activity. 7. Sulphonium compounds, glucosinolates and antithyroid compounds with no thionamide group, including potassium thiocyanate, had no marked effect on the activity of the enzyme.
D000577:Amides / Q000494:pharmacology*; D000818:Animals; D002645:Chickens; D066298:In Vitro Techniques; D007700:Kinetics; D008862:Microsomes, Liver / Q000201:enzymology*; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors*; D013854:Thioamides / Q000494:pharmacology*
D000577:Amides; D013854:Thioamides; D010089:Oxidoreductases, N-Demethylating; C023186:trimethylamine dehydrogenase