Effect of methimazole on the activity of mushroom tyrosinase.
Methimazole (1-methyl-2-mercaptoimidazole) inhibits both the mono- and the o-dihydroxyphenolase activities of mushroom tyrosinase when assayed spectrophotometrically. With DL-3,4-dihydroxyphenylalanine as substrate, the inhibition was found to be a mixed-type one with Ki 4.6 X 10(-6) M. We found that methimazole can interact with the oxidation products of o-dihydroxyphenols, probably with o-quinones, to form a conjugate. The conjugate formed between methimazole and o-benzoquinone was separated by chromatography on Sephadex G-10 and was characterized by an absorption maximum at 248-260 nm. Our data suggest that methimazole inhibits mushroom tyrosinase activity in two ways: by conjugating with o-quinones, thereby causing an apparent inhibition in pigmented product formation as judged by the spectrophotometric assay; and by chelating copper at the active site of the enzyme, as judged by assaying the release of 3HHO from L-[3,5-3H]tyrosine.
D001487:Basidiomycota / Q000187:drug effects / Q000201:enzymology*; D001665:Binding Sites; D004156:Catechol Oxidase / Q000037:antagonists & inhibitors*; D002396:Catechols / Q000378:metabolism; D002850:Chromatography, Gel; D003300:Copper / Q000378:metabolism; D003545:Cysteine / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D008713:Methimazole / Q000494:pharmacology*; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D011809:Quinones / Q000378:metabolism; D013053:Spectrophotometry
D002396:Catechols; D011809:Quinones; D008713:Methimazole; D004295:Dihydroxyphenylalanine; D003300:Copper; D004156:Catechol Oxidase; D014442:Monophenol Monooxygenase; D003545:Cysteine