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. 1986 Apr 1;235(1):91–96. doi: 10.1042/bj2350091

Effect of methimazole on the activity of mushroom tyrosinase.

A Andrawis, V Kahn
PMCID: PMC1146653  PMID: 3091005

Abstract

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cohen G., Heikkila R. E., Allis B., Cabbat F., Dembiec D., MacNamee D., Mytilineou C., Winston B. Destruction of sympathetic nerve terminals by 6-hydroxydopamine: protection by 1-phenyl-3-(2-thiazolyl)-2-thiourea, diethyldithiocarbamate, methimazole, cysteamine, ethanol and n-butanol. J Pharmacol Exp Ther. 1976 Nov;199(2):336–352. [PubMed] [Google Scholar]
  2. Duckworth H. W., Coleman J. E. Physicochemical and kinetic properties of mushroom tyrosinase. J Biol Chem. 1970 Apr 10;245(7):1613–1625. [PubMed] [Google Scholar]
  3. Hanlon D. P., Shuman S. Copper ion binding and enzyme inhibitory properties of the antithyroid drug methimazole. Experientia. 1975 Sep 15;31(9):1005–1006. doi: 10.1007/BF02326924. [DOI] [PubMed] [Google Scholar]
  4. MASON H. S. OXIDASES. Annu Rev Biochem. 1965;34:595–634. doi: 10.1146/annurev.bi.34.070165.003115. [DOI] [PubMed] [Google Scholar]
  5. Palmer J. K., Roberts J. B. Inhibition of banana polyphenoloxidase by 2-mercaptobenzothiazole. Science. 1967 Jul 14;157(3785):200–201. doi: 10.1126/science.157.3785.200. [DOI] [PubMed] [Google Scholar]
  6. Pierpoint W. S. The enzymic oxidation of chlorogenic acid and some reactions of the quinone produced. Biochem J. 1966 Feb;98(2):567–580. doi: 10.1042/bj0980567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Pierpoint W. S. o-Quinones formed in plant extracts. Their reaction with bovine serum albumin. Biochem J. 1969 May;112(5):619–629. doi: 10.1042/bj1120619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Pomerantz S. H. The tyrosine hydroxylase activity of mammalian tyrosinase. J Biol Chem. 1966 Jan 10;241(1):161–168. [PubMed] [Google Scholar]
  9. Pomerantz S. H. Tyrosine hydroxylation catalyzed by mammalian tyrosinase: an improved method of assay. Biochem Biophys Res Commun. 1964 Jun 1;16(2):188–194. doi: 10.1016/0006-291x(64)90359-6. [DOI] [PubMed] [Google Scholar]
  10. Pomerantz S. H., Warner M. C. 3,4-dihydroxy-L-phenylalanine as the tyrosinase cofactor. Occurrence in melanoma and binding constant. J Biol Chem. 1967 Nov 25;242(22):5308–5314. [PubMed] [Google Scholar]
  11. ROSTON S. Reaction of the sulfhydryl group with an oxidation product of beta-3,4-dihydroxyphenyl-L-alanine. J Biol Chem. 1960 Apr;235:1002–1004. [PubMed] [Google Scholar]
  12. Sanada H., Suzue R., Nakashima Y., Kawada S. Effect of thiol compounds on melanin formation by tyrosinase. Biochim Biophys Acta. 1972 Jan 28;261(1):258–266. doi: 10.1016/0304-4165(72)90336-4. [DOI] [PubMed] [Google Scholar]
  13. Seiji M., Yoshida T., Itakura H., Irimajiri T. Inhibition of melanin formation by sulfhydryl compounds. J Invest Dermatol. 1969 Mar;52(3):280–286. [PubMed] [Google Scholar]
  14. Stolk J. M., Hanlon D. P. Inhibition of brain dopamine- -hydroxylase activity by methimazole. Life Sci II. 1973 May 8;12(9):417–423. doi: 10.1016/0024-3205(73)90324-x. [DOI] [PubMed] [Google Scholar]
  15. Tomita Y., Seiji M., Igarashi A. The hydroxyl radical is not involved with tyrosinase inactivation. J Dermatol. 1980 Oct;7(5):377–380. doi: 10.1111/j.1346-8138.1980.tb01986.x. [DOI] [PubMed] [Google Scholar]

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