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Regulation of Melanin Biosynthesis in the Human Epidermis by Tetrahydrobiopterin
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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Citations
Cited by
Melanin pigmentation in mammalian skin and its hormonal regulation
Slominski, A., Tobin, D. J., Shibahara, S., & Wortsman, J. (2004) · Physiological Reviews · doi:10.1152/physrev.00044.2003 · Cited by 2,015
Neuroendocrinology of the Skin1
Slominski, A., & Wortsman, J. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.5.0410 · Cited by 727
Slominski (2012) · doi:10.1007/978-3-642-19683-6_1 · Cited by 461
How UV Light Touches the Brain and Endocrine System Through Skin, and Why
Slominski, A. T., Zmijewski, M. A., Plonka, P. M., Szaflarski, J. P., & Paus, R. (2018) · Endocrinology · doi:10.1210/en.2017-03230 · Cited by 452
Regulation of melanogenesis – controversies and new concepts
Schallreuter, K. U., Kothari, S., Chavan, B., & Spencer, J. D. (2008) · Experimental Dermatology · doi:10.1111/j.1600-0625.2007.00675.x · Cited by 352
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Metadata
- Authors
- Schallreuter, K. U., Wood, J. M., Pittelkow, M. R., Gütlich, M., Lemke, K. R., Rödl, W., Swanson, N. N., Hitzemann, K., & Ziegler, I.
- Venue
- Science
- Published
- 1994-03-11
- Volume
- 263
- Issue
- 5152
- Pages
- 1444-1446
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2072512993
- Cited by
- 350
- References
- 0
- FWCI
- 4.42
- Type
- journal article
- Language
- en
- Open access
- closed
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- Schallreuter, K. U., Wood, J. M., Pittelkow, M. R., Gütlich, M., Lemke, K. R., Rödl, W., Swanson, N. N., Hitzemann, K., & Ziegler, I. (1994). Regulation of Melanin Biosynthesis in the Human Epidermis by Tetrahydrobiopterin. Science. https://doi.org/10.1126/science.8128228
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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