A review of recent advances on the regulation of pigmentation in the human epidermis.
It has been recognised that the active transport of L-phenylalanine and its autocrine turnover to L-tyrosine via phenylalanine hydroxylase in the cytosol of epidermal melanocytes provides the majority of the L-tyrosine pool for melanogenesis. In this context, it has been shown that the cofactor 6(R)-L-erythro 5,6,7,8 tetrahydrobiopterin (6BH4) is produced de novo, recycled and regulated in both epidermal melanocytes and keratinocytes to control tyrosine hydroxylase, phenylalanine hydroxylase and tyrosinase activity. Inhibition of the enzymes by excessive 6BH4 levels is reversible with alpha-MSH by specific complex formation between 6BH4 and the hormone. This direct mechanism of alpha-MSH is supported by the presence of the entire POMC processing system in the melanosome indicating a receptor independent control of eumelanogenesis. Finally, the role of tyrosinase, TRP-1 and TRP2 is discussed in association with oxidative stress specifically related to hydrogen peroxide. These recent findings are based on detailed investigations of the depigmentation disorder vitiligo and Hermanský-Pudlák syndrome.
Schallreuter
K U
KU
Clinical and Experimental Dermatology, Department of Biomedical Sciences, University of Bradford, West Yorkshire, UK. K.Schallreuter@bradford.ac.uk
D016115:Albinism, Oculocutaneous / Q000378:metabolism; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004789:Enzyme Activation; D004817:Epidermis / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism; D020460:Melanosomes / Q000378:metabolism; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism; D018384:Oxidative Stress; D010088:Oxidoreductases; D010649:Phenylalanine / Q000378:metabolism; D010651:Phenylalanine Hydroxylase / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D044469:Racial Groups; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012880:Skin Pigmentation / Q000502:physiology*; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014820:Vitiligo / Q000378:metabolism; D000521:alpha-MSH / Q000502:physiology
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D001708:Biopterins; D014443:Tyrosine; D010649:Phenylalanine; D000521:alpha-MSH; D004295:Dihydroxyphenylalanine; D011333:Pro-Opiomelanocortin; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; D010651:Phenylalanine Hydroxylase; D014446:Tyrosine 3-Monooxygenase; C489799:TYRP1 protein, human; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase; C003402:sapropterin