Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1990 Dec 1;272(2):459–463. doi: 10.1042/bj2720459

Effect of pH on the oxidation pathway of alpha-methyldopa catalysed by tyrosinase.

P Serna Rodríguez 1, J N Rodríguez López 1, J Tudela 1, R Varón 1, F García Cánovas 1
PMCID: PMC1149721  PMID: 2125208

Abstract

This paper deals with the quantitative description of the effect of pH on the oxidation pathway of alpha-methyldopa. Tyrosinase catalyses the oxidation by molecular oxygen of alpha-methyldopa to o-alpha-methyldopaquinone, which evolves non-enzymically through a branched pathway with cyclization or hydroxylation reactions. The intermediates of the hydroxylation branch have been identified, and the corresponding rate constants have been determined. These compounds, which have been detected in melanosomes and in tumour cells, have great cytotoxic power and could have physiological significance in acidic media.

Full text

PDF
459

Selected References

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

  1. Burnett J. B. The tyrosinases of mouse melanoma. Isolation and molecular properties. J Biol Chem. 1971 May 25;246(10):3079–3091. [PubMed] [Google Scholar]
  2. Cánovas F. G., García-Carmona F., Sánchez J. V., Pastor J. L., Teruel J. A. The role of pH in the melanin biosynthesis pathway. J Biol Chem. 1982 Aug 10;257(15):8738–8744. [PubMed] [Google Scholar]
  3. Galindo J. D., Pedreño E., Garcia-Carmona F., Garcia-Cánovas F., Solano Muñoz F., Lozano J. A. Steady-state study of the mechanism of dopa-oxidase activity of tyrosinase. Int J Biochem. 1983;15(12):1455–1461. doi: 10.1016/0020-711x(83)90078-2. [DOI] [PubMed] [Google Scholar]
  4. Graham D. G., Jeffs P. W. The role of 2,4,5-trihydroxyphenylalanine in melanin biosynthesis. J Biol Chem. 1977 Aug 25;252(16):5729–5734. [PubMed] [Google Scholar]
  5. Graham D. G., Tiffany S. M., Vogel F. S. The toxicity of melanin precursors. J Invest Dermatol. 1978 Feb;70(2):113–116. doi: 10.1111/1523-1747.ep12541249. [DOI] [PubMed] [Google Scholar]
  6. Harrison W. H., Gray R. M., Solomon L. M. Incorporation of L-dopa, L-alpha-methyldopa and DL-isoproterenol into guinea pig hair. Acta Derm Venereol. 1974;54(4):249–253. [PubMed] [Google Scholar]
  7. Hedley D. W., Jorgensen H. B. Flow cytometric measurement of intracellular pH in B16 tumors: intercell variance and effects of pretreatment with glucose. Exp Cell Res. 1989 Jan;180(1):106–116. doi: 10.1016/0014-4827(89)90216-4. [DOI] [PubMed] [Google Scholar]
  8. Jiménez M., Garcia-Canovas F., Garcia-Carmona F., Tudela J., Iborra J. L. Study of alpha-methyldopa oxidation by tyrosinase. Int J Biochem. 1986;18(1):39–47. doi: 10.1016/0020-711x(86)90006-6. [DOI] [PubMed] [Google Scholar]
  9. Langston J. W. Neuromelanin-containing neurons are selectively vulnerable in parkinsonism. Trends Pharmacol Sci. 1988 Oct;9(10):347–348. doi: 10.1016/0165-6147(88)90248-9. [DOI] [PubMed] [Google Scholar]
  10. Liang Y. O., Plotsky P. M., Adams R. N. Isolation and identificaton of an in vivo reaction product of 6-hydroxydopamine. J Med Chem. 1977 Apr;20(4):581–583. doi: 10.1021/jm00214a026. [DOI] [PubMed] [Google Scholar]
  11. MASON H. S. Mechanisms of oxygen metabolism. Adv Enzymol Relat Subj Biochem. 1957;19:79–233. doi: 10.1002/9780470122648.ch2. [DOI] [PubMed] [Google Scholar]
  12. Nishioka K. Particulate tyrosinase of human malignant melanoma. Solubilization, purification following trypsin treatment, and characterization. Eur J Biochem. 1978 Apr;85(1):137–146. doi: 10.1111/j.1432-1033.1978.tb12221.x. [DOI] [PubMed] [Google Scholar]
  13. Saeki H., Oikawa A. Stimulation by ionophores of tyrosinase activity of mouse melanoma cells in culture. J Invest Dermatol. 1985 Nov;85(5):423–425. doi: 10.1111/1523-1747.ep12277091. [DOI] [PubMed] [Google Scholar]
  14. Saeki H., Oikawa A. Stimulation of tyrosinase activity of cultured melanoma cells by lysosomotropic agents. J Cell Physiol. 1983 Jul;116(1):93–97. doi: 10.1002/jcp.1041160114. [DOI] [PubMed] [Google Scholar]
  15. Ward-Routledge C., Marsden C. A. Adrenaline in the CNS and the action of antihypertensive drugs. Trends Pharmacol Sci. 1988 Jun;9(6):209–214. doi: 10.1016/0165-6147(88)90087-9. [DOI] [PubMed] [Google Scholar]
  16. Wick M. M. An experimental approach to the chemotherapy of melanoma. J Invest Dermatol. 1980 Feb;74(2):63–65. doi: 10.1111/1523-1747.ep12519812. [DOI] [PubMed] [Google Scholar]
  17. Wick M. M., Byers L., Frei E., 3rd L-dopa: selective toxicity for melanoma cells in vitro. Science. 1977 Jul 29;197(4302):468–469. doi: 10.1126/science.877570. [DOI] [PubMed] [Google Scholar]
  18. Wick M. M., Kramer R. A., Gorman M. Enhancement of L-dopa incorporation into melanoma by dopa decarboxylase inhibition. J Invest Dermatol. 1978 Jun;70(6):358–360. doi: 10.1111/1523-1747.ep12543559. [DOI] [PubMed] [Google Scholar]
  19. Wick M. M. Levodopa and dopamine analogs: melanin precursors as antitumor agents in experimental human and murine leukemia. Cancer Treat Rep. 1979 Jun;63(6):991–997. [PubMed] [Google Scholar]
  20. Wike-Hooley J. L., Haveman J., Reinhold H. S. The relevance of tumour pH to the treatment of malignant disease. Radiother Oncol. 1984 Dec;2(4):343–366. doi: 10.1016/s0167-8140(84)80077-8. [DOI] [PubMed] [Google Scholar]
  21. Yu R. J., Van Scott E. J. Substrate identity in mammalian melanogenesis. J Invest Dermatol. 1973 Apr;60(4):234–237. doi: 10.1111/1523-1747.ep12724529. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES