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Regulation of Melanin Biosynthesis in the Human Epidermis by Tetrahydrobiopterin

Karin U. Schallreuter, John M. Wood, Mark R. Pittelkow, Markus Gütlich, K. Regina Lemke, Wolfgang Rödl, Norma N. Swanson, Karen Hitzemann and Irmgard Ziegler
Science
New Series, Vol. 263, No. 5152 (Mar. 11, 1994), pp. 1444-1446
Stable URL: http://www.jstor.org/stable/2883325
Page Count: 3
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Regulation of Melanin Biosynthesis in the Human Epidermis by Tetrahydrobiopterin
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Abstract

The participation of (6R) 5,6,7,8-tetrahydrobiopterin (6-BH$_4$) in regulating the tyrosine supply for melanin biosynthesis was investigated by the examination of human keratinocytes, melanocytes, and epidermal suction blisters from normal human skin and from patients with the depigmentation disorder vitiligo. Cells, as well as total epidermis, contained high phenylalanine hydroxylase activities and also displayed the capacity to synthesize and recycle 6-BH$_4$, the essential cofactor for this enzyme. In vitiligo, 4a-hydroxy-BH$_4$ dehydratase activity was extremely low or absent, yielding an accumulation of the nonenzymatic by-product 7-tetrahydrobiopterin (7-BH$_4$) at concentrations up to 8 × 10$^{-6}$ M in the epidermis. This by-product is a potent competitive inhibitor in the phenylalanine hydroxylase reaction with an inhibition constant of 10$^{-6}$ M. Thus, 6-BH$_4$ seems to control melanin biosynthesis in the human epidermis, whereas 7-BH$_4$ may initiate depigmentation in patients with vitiligo.

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