Pteridines in the control of pigmentation

Area of Science:

• Biochemistry
• Dermatology
• Photobiology

Background:

• The human epidermis synthesizes L-tyrosine from L-phenylalanine via a pathway regulated by GTP-cyclohydrolase 1 (GTP-CH-1).
• GTP-CH-1 is the rate-limiting enzyme for the de novo synthesis of (6R)L-erythro-5,6,7,8-tetrahydrobiopterin (6-BH4), an essential cofactor.
• 6-BH4 controls L-tyrosine production by phenylalanine hydroxylase (PAH) and its synthesis can be induced by factors like tumor necrosis factor-alpha (TNF alpha).

Purpose of the Study:

• To investigate the influence of UVB irradiation on the L-tyrosine metabolic pathway in human epidermis.
• To assess the role of UVB in inducing key enzymes and cofactors involved in L-tyrosine synthesis.
• To compare the UVB-induced metabolic response across different photo skin types.

Main Methods:

• Healthy volunteers (12) with Fitzpatrick skin types I-VI were exposed to a standardized UVB dose (1 minimal erythema dose).
• Epidermal suction blister tissues were collected before (0 h) and after UVB exposure (24 and 72 h).
• Measurements included TNF alpha release, GTP-CH-1 activity, total 6-biopterin levels, and PAH activity.

Main Results:

• UVB irradiation significantly increased TNF alpha release, GTP-CH-1 activity, total 6-biopterin levels, and PAH activity in all subjects.
• These changes indicate an enhanced metabolic pathway for L-tyrosine production following UVB exposure.
• The response of this metabolic cascade was more pronounced in individuals with fair photo skin types (I-III) compared to those with darker skin types (IV-VI).

Conclusions:

• UVB irradiation directly influences and enhances the metabolic pathway for L-tyrosine production in the human epidermis.
• This UVB-controlled L-tyrosine supply is a significant factor in de novo melanogenesis.
• Skin photo type modulates the epidermal response to UVB in this metabolic pathway.