Pteridines in the Control of Pigmentation

Abstract

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.