Pteridines in the control of pigmentation.
The influence of UVB irradiation on the metabolic pathway for the production of L-tyrosine from L-phenylalanine in the human epidermis has been examined in 12 healthy volunteers with photo skin types I-VI (Fitzpatrick classification). This metabolic pathway involves the induction of GTP-cyclohydrolase 1 (GTP-CH-1), the rate-limiting enzyme for de novo synthesis of (6R)L-erythro-5,6,7,8-tetrahydrobiopterin (6-BH4). This essential cofactor controls the production of L-tyrosine from L-phenylalanine via phenylalanine hydroxylase (PAH). The de novo synthesis of 6-BH4 depends on the induction of GTP-CH-1, e.g., by tumor necrosis factor-alpha (TNF alpha). Epidermal suction blister tissues were taken before (0 h) and after (24 and 72 h) UVB exposure with a standardized dosage [1 minimal erythema dose (MED)]. In all cases, there was a significant increase in TNF alpha release, GTP-CH-1 activity, total 6-biopterin level, and PAH activity, indicative of enhanced L-tyrosine production. The response of this metabolic cascade over baseline activities was pronounced in fair photo skin types (I-III) compared to dark skin (IV-VI). Taken together, our results suggest that UVB can control the direct supply of L-tyrosine in the epidermis, and this process may represent an important factor in de novo melanogenesis.
Schallreuter
K U
KU
Department of Biomedical Sciences, University of Bradford, U.K.
Schulz-Douglas
V
V
Bünz
A
A
Beazley
W
W
Körner
C
C
D000328:Adult; D001708:Biopterins / Q000031:analogs & derivatives / Q000096:biosynthesis; D005122:Exudates and Transudates / Q000737:chemistry / Q000528:radiation effects; D005260:Female; D006136:GTP Cyclohydrolase / Q000528:radiation effects; D006801:Humans; D008297:Male; D010651:Phenylalanine Hydroxylase / Q000378:metabolism / Q000528:radiation effects; D010859:Pigmentation Disorders / Q000517:prevention & control*; D011621:Pteridines / Q000627:therapeutic use*; D012872:Skin Diseases, Vesiculobullous / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014466:Ultraviolet Rays
D011621:Pteridines; D014409:Tumor Necrosis Factor-alpha; C077911:2-amino-4-hydroxy-7-(dihydroxypropyl)-5,6,7,8-tetrahydrobiopterin; D001708:Biopterins; D010651:Phenylalanine Hydroxylase; D006136:GTP Cyclohydrolase; C003402:sapropterin