Regulation of melanin biosynthesis in the human epidermis by tetrahydrobiopterin
| Autor: | M Gütlich, Mark R. Pittelkow, K Hitzemann, K. R. Lemke, I Ziegler, Norma N. Swanson, W Rödl, John M. Wood, Karin U. Schallreuter |
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| Rok vydání: | 1994 |
| Předmět: |
Keratinocytes
Phenylalanine hydroxylase Vitiligo Melanocyte Biology Melanin Depigmentation medicine Humans GTP Cyclohydrolase Cells Cultured Melanins Multidisciplinary integumentary system Epidermis (botany) Phenylalanine Hydroxylase Cell Differentiation Tetrahydrobiopterin medicine.disease Biopterin medicine.anatomical_structure Biochemistry biology.protein Melanocytes Tyrosine medicine.symptom Epidermis Keratinocyte medicine.drug |
| Zdroj: | Science (New York, N.Y.). 263(5152) |
| ISSN: | 0036-8075 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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