methimazole and 2-mercaptoimidazole

Lactoperoxidase (LPO) belongs to mammalian heme peroxidase superfamily, which also includes myeloperoxidase (MPO), eosinophil peroxidase (EPO), and thyroid peroxidase (TPO). LPO catalyzes the oxidation of a number of substrates including thiocyanate while TPO catalyzes the biosynthesis of thyroid hormones. LPO is also been shown to catalyze the biosynthesis of thyroid hormones indicating similar functional and structural properties. The binding studies showed that 2-mercaptoimidazole (MZY) bound to LPO with a dissociation constant of 0.63 µM. The inhibition studies showed that the value of IC

Topics: Binding Sites; Crystallography, X-Ray; Ethylenethiourea; Heme; Humans; Lactoperoxidase; Methimazole; Protein Conformation; Substrate Specificity; Sulfur; Thyroid Gland; Thyroid Hormones

Phosphate buffer solutions of two dipeptides prevalent in striated muscle, L-carnosine (beta-alanyl-L-histidine) and L-anserine (beta-alanyl-L-1-methylhistidine), produce active oxygen species as measured by bleaching of N,N-dimethyl-4-nitrosoaniline (RNO). Activity is enhanced 5-14-fold in the presence of 2-mercaptoimidazoles such as ergothioneine, carbimazole (3-methyl-2-mercaptoimidazole-1-carboxylate), methimazole (2-mercapto-1-methylimidazole) and 2-mercaptoimidazole but only slightly by thiourea and dimethylthiourea. Activity is proportional to carnosine concentration and to mercaptoimidazole concentration at a fixed concentration of the second component. A variety of imidazoles closely related to carnosine and anserine are inactive, even after addition of transition metal ions. Activity is moderately increased above the pKa of the carnosine imidazole ring (pH 7.2, 7.5 and 8.0) versus below the pKa (pH 6.5 and 6.8). Activity is slightly increased by addition of copper or cobalt ions but not by addition of ferrous or ferric ions. Activity is decreased by Chelex 100 pretreatment of phosphate buffer and stimulated when copper or cobalt ions are added to the chelated buffer but there is no significant stimulation by ferric ions. Catalase eliminates most activity but superoxide dismutase has little effect. We propose that metal-carnosine and metal-anserine complexes produce superoxide and also serve as superoxide dismutases with resultant accumulation of hydrogen peroxide. An unidentified radical produced from hydrogen peroxide subsequently bleaches RNO. From the biological distributions of carnosine, anserine and ergothioneine, we infer that deleterious effects are probably minimal under normal physiological circumstances due to tissue and cellular compartmentalization and to sequestration of these compounds and transition metal ions.

Topics: Anserine; Carbimazole; Carnosine; Catalase; Cobalt; Copper; Ergothioneine; Ethylenethiourea; Hydrogen-Ion Concentration; Imidazoles; Methimazole; Mutagenicity Tests; Reactive Oxygen Species; Salmonella; Solutions; Sulfhydryl Compounds; Superoxides

Topics: Animals; Antithyroid Agents; Ethylenethiourea; Methimazole; Mice; Radiation Protection; Whole-Body Irradiation