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Science 11 March 1994:
Vol. 263. no. 5152, pp. 1444 - 1446
DOI: 10.1126/science.8128228
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Articles

Science, Vol 263, Issue 5152, 1444-1446
Copyright © 1994 by American Association for the Advancement of Science

articles

Regulation of melanin biosynthesis in the human epidermis by tetrahydrobiopterin

KU Schallreuter, JM Wood, MR Pittelkow, M Gutlich, KR Lemke, W Rodl, NN Swanson, K Hitzemann, and I Ziegler

Department of Dermatology, University of Hamburg, Germany.

The participation of (6R) 5,6,7,8-tetrahydrobiopterin (6-BH4) 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-BH4, the essential cofactor for this enzyme. In vitiligo, 4a-hydroxy-BH4 dehydratase activity was extremely low or absent, yielding an accumulation of the nonenzymatic by-product 7-tetrahydrobiopterin (7-BH4) at concentrations up to 8 x 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-BH4 seems to control melanin biosynthesis in the human epidermis, whereas 7-BH4 may initiate depigmentation in patients with vitiligo.


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