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- Title
α-MSH Can Control the Essential Cofactor 6-Tetrahydrobiopterin in Melanogenesis.
- Authors
SCHALLREUTER, KARIN U.; MOORE, JEREMY; TOBIN, DESMOND J.; GIBBONS, NICHOLAS J.P.; MARSHALL, HARRIET S.; JENNER, TRACEY; BEAZLEY, WAYNE D.; WOOD, JOHN M.
- Abstract
ABSTRACT: In the human epidermis both keratinocytes and melanocytes express POMC m-RNA. Immunohistochemical studies of both cell types demonstrate significantly higher levels of α-MSH in melanocytes than in keratinocytes. Both cell types also hold the full capacity for de novo synthesis/recycling of the essential cofactor (6R)-l-erythro-5,6,7,8-tetrahydrobiopterin (6BH4). 6BH4 is critical for the hydroxylation of the aromatic amino acids l-phenylalanine, l-tyrosine, and l-tryptophan, for nitric oxide production and in various immune modulatory processes. Recently it was shown that tyrosinase activity is regulated by 6BH4 through a specific allosteric inhibition. The tyrosinase/6BH4 inhibition can be activated by 1:1 complex formation between 6BH4 and α-MSH, but an excess of α-MSH over 6BH4 can inhibit tyrosinase due to complex formation by tyr2 in the α-MSH sequence. In both melanocytes and keratinocytes 6BH4 controls the l-tyrosine supply via phenylalanine hydroxylase (PAH). Recently we were able to show that the cellular uptake of l-phenylalanine and its intracellular turnover to l-tyrosine is crucial for melanogenesis. α-MSH can promote the production of l-tyrosine via PAH due to activation of the PAH tetramer to the more active dimer by removing 6BH4 from the regulatory binding domain on the enzyme. In conclusion, α-MSH can control (1) intracellular l-tyrosine formation from l-phenylalanine in both melanocytes and keratinocytes, and (2) tyrosinase activity, directly, in melanocytes.
- Publication
Annals of the New York Academy of Sciences, 1999, Vol 885, Issue 1, p329
- ISSN
0077-8923
- Publication type
Article
- DOI
10.1111/j.1749-6632.1999.tb08688.x