PMID: 10816664

alpha-MSH can control the essential cofactor 6-tetrahydrobiopterin in melanogenesis .

In the human epidermis both keratinocytes and melanocytes express POMC m-RNA .

Immunohistochemical studies of both cell types demonstrate significantly higher levels of alpha-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 alpha-MSH , but an excess of alpha-MSH over 6BH4 can inhibit tyrosinase due to complex formation by tyr2 in the alpha-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 .

alpha-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 , alpha-MSH can control ( 1 ) intracellular L-tyrosine formation from L-phenylalanine in both melanocytes and keratinocytes , and ( 2 ) tyrosinase activity , directly , in melanocytes .